Pub Date : 2025-02-25DOI: 10.1016/j.alcohol.2025.02.003
Callon M. Williams , Nadine R. Mastroleo , Mark F. Lenzenweger , Emily L. Zale
Alcohol use, cannabis use, and pain are public health concerns among emerging adults (18–24 years old). Co-use of alcohol and cannabis is of particular concern since individuals who co-use alcohol and cannabis use more of each substance and experience greater substance-related harm. Pain and substance use frequently co-occur, and a growing body of literature indicates pain is unique risk factor for substance use. The goal of the current study was to examine moderate/severe pain (vs. no/low pain) as a prospective predictor of engaging in co-use of alcohol and cannabis among emerging adults, and to test sex as a moderator of this hypothesized relationship. Data were drawn from Waves 1–5 of the Population Assessment of Tobacco and Health Study (n = 3544). Unadjusted logistic regression revealed that those with moderate/severe pain at baseline were 1.4 times more likely to engage in past-month co-use of alcohol and cannabis over the next four years (p = .046). The effects of pain on co-use were no longer significant after inclusion of covariates and a pain∗sex interaction term, which was also nonsignificant (ps > .05). These findings provide initial support for pain as a risk factor for engaging in co-use of alcohol and cannabis during emerging adulthood. Future research should continue investigating how pain may motivate co-use of alcohol and cannabis, exploring how pain is associated with other measures of co-use, and determining how providers can incorporate pain-substance use psychoeducation for emerging adults in clinical settings.
{"title":"Pain predicts past-month co-use of alcohol and cannabis among emerging adults: Results from the Population Assessment of Tobacco and Health (PATH) Study","authors":"Callon M. Williams , Nadine R. Mastroleo , Mark F. Lenzenweger , Emily L. Zale","doi":"10.1016/j.alcohol.2025.02.003","DOIUrl":"10.1016/j.alcohol.2025.02.003","url":null,"abstract":"<div><div>Alcohol use, cannabis use, and pain are public health concerns among emerging adults (18–24 years old). Co-use of alcohol and cannabis is of particular concern since individuals who co-use alcohol and cannabis use more of each substance and experience greater substance-related harm. Pain and substance use frequently co-occur, and a growing body of literature indicates pain is unique risk factor for substance use. The goal of the current study was to examine moderate/severe pain (vs. no/low pain) as a prospective predictor of engaging in co-use of alcohol and cannabis among emerging adults, and to test sex as a moderator of this hypothesized relationship. Data were drawn from Waves 1–5 of the Population Assessment of Tobacco and Health Study (<em>n</em> = 3544). Unadjusted logistic regression revealed that those with moderate/severe pain at baseline were 1.4 times more likely to engage in past-month co-use of alcohol and cannabis over the next four years (<em>p</em> = .046). The effects of pain on co-use were no longer significant after inclusion of covariates and a pain∗sex interaction term, which was also nonsignificant (<em>ps</em> > .05). These findings provide initial support for pain as a risk factor for engaging in co-use of alcohol and cannabis during emerging adulthood. Future research should continue investigating how pain may motivate co-use of alcohol and cannabis, exploring how pain is associated with other measures of co-use, and determining how providers can incorporate pain-substance use psychoeducation for emerging adults in clinical settings.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"124 ","pages":"Pages 111-119"},"PeriodicalIF":2.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-11DOI: 10.1016/j.alcohol.2025.02.002
David L. Haggerty , Sara E.M.M.F. Badaro , Eva Nadpara , Carly B. Fabian , Karina P. Abrahao , David M. Lovinger , Max E. Joffe
Open source devices are becoming widely used in behavioral neuroscience. Despite their advantages in cost effectiveness, modularity, and customization, measurements obtained using newly developed devices may not always recapitulate measurements from existing and validated equipment, potentially due to the materials used in manufacture. In this study, we evaluated a commonly used open-source optical lickometer that delivers fluid via a Hydropac® plastic valve in a multi-site intermittent access two-bottle choice (IA2BC) paradigm for alcohol consumption. Mice were tested with both traditional metal sippers and plastic sippers equipped with Hydropac® valves to assess differences in alcohol intake, preference, and total fluid consumption. Our findings revealed that mice displayed reduced intake and preference for alcohol (10–20% v/v) delivered via the Hydropac® containing plastic sippers. Notably, the effect was observed at both testing sites, suggesting a generalizable phenomenon. The decreased intake was also specific to alcohol, as water, quinine, and sucrose consumption were unaffected by sipper type. To investigate the underlying cause of the reduced alcohol consumption, we pre-incubated Hydropac® valves in 20% alcohol and found that the pre-treated alcohol reduced intake even when delivered via metal sippers. This suggests that prolonged interaction between alcohol and the components of the Hydropac® valves alter the fluid, likely by generating unpalatable contaminants. These results highlight a limitation of using plastic sippers in long-term alcohol self-administration studies. While these devices may remain suitable for limited access paradigms their use in extended access protocols may compromise data integrity. Our study underscores the need for rigorous validation of open-source hardware in each research project.
{"title":"Impact of plastic sipper devices on alcohol self-administration in rodents: Limitations for long-term access paradigms","authors":"David L. Haggerty , Sara E.M.M.F. Badaro , Eva Nadpara , Carly B. Fabian , Karina P. Abrahao , David M. Lovinger , Max E. Joffe","doi":"10.1016/j.alcohol.2025.02.002","DOIUrl":"10.1016/j.alcohol.2025.02.002","url":null,"abstract":"<div><div>Open source devices are becoming widely used in behavioral neuroscience. Despite their advantages in cost effectiveness, modularity, and customization, measurements obtained using newly developed devices may not always recapitulate measurements from existing and validated equipment, potentially due to the materials used in manufacture. In this study, we evaluated a commonly used open-source optical lickometer that delivers fluid via a Hydropac® plastic valve in a multi-site intermittent access two-bottle choice (IA2BC) paradigm for alcohol consumption. Mice were tested with both traditional metal sippers and plastic sippers equipped with Hydropac® valves to assess differences in alcohol intake, preference, and total fluid consumption. Our findings revealed that mice displayed reduced intake and preference for alcohol (10–20% v/v) delivered via the Hydropac® containing plastic sippers. Notably, the effect was observed at both testing sites, suggesting a generalizable phenomenon. The decreased intake was also specific to alcohol, as water, quinine, and sucrose consumption were unaffected by sipper type. To investigate the underlying cause of the reduced alcohol consumption, we pre-incubated Hydropac® valves in 20% alcohol and found that the pre-treated alcohol reduced intake even when delivered via metal sippers. This suggests that prolonged interaction between alcohol and the components of the Hydropac® valves alter the fluid, likely by generating unpalatable contaminants. These results highlight a limitation of using plastic sippers in long-term alcohol self-administration studies. While these devices may remain suitable for limited access paradigms their use in extended access protocols may compromise data integrity. Our study underscores the need for rigorous validation of open-source hardware in each research project.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"125 ","pages":"Pages 17-24"},"PeriodicalIF":2.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-10DOI: 10.1016/j.alcohol.2025.02.001
Amine Bahi
Depression and anxiety disorders are often exacerbated by social stress, necessitating the exploration of molecular mechanisms underlying stress resilience. Tissue plasminogen activator (tPA), a serine protease with pleiotropic effects in the brain, plays a critical role in modulating neuroplasticity and stress responses. This study investigates the behavioral and molecular effects of tPA gain-of-function in a social stress paradigm in male C57BL/6 mice using lentiviral vectors. Behaviorally, hippocampal tPA gain-of-function mitigated depression-like responses in the novelty-suppressed feeding, sucrose splash, tail suspension, and forced swim tests following exposure to chronic social stress. Additionally, in a two-bottle choice drinking paradigm, tPA overexpression reduced social stress-induced ethanol intake and preference, suggesting a role in dampening maladaptive coping behaviors. However, analysis of tastants’ intake and preference revealed no significant effects of tPA overexpression, indicating that it does not influence hedonic responses under stress conditions. Molecularly, tPA overexpression preserved hippocampal tPA mRNA expression and maintained levels of mature brain-derived neurotrophic factor in the hippocampus despite chronic stress exposure. These findings highlight the potential neuroprotective effects of tPA in maintaining hippocampal plasticity and mitigating stress-induced dysregulation of critical neurotrophic pathways. Collectively, this study underscores the potential of tPA as a therapeutic target for stress-induced mood and substance use disorders by modulating behavioral and neurobiological responses to chronic social stress.
{"title":"Hippocampal overexpression of tissue-type plasminogen activator “tPA” attenuates social defeat-induced depression and ethanol related behavior in mice","authors":"Amine Bahi","doi":"10.1016/j.alcohol.2025.02.001","DOIUrl":"10.1016/j.alcohol.2025.02.001","url":null,"abstract":"<div><div>Depression and anxiety disorders are often exacerbated by social stress, necessitating the exploration of molecular mechanisms underlying stress resilience. Tissue plasminogen activator (tPA), a serine protease with pleiotropic effects in the brain, plays a critical role in modulating neuroplasticity and stress responses. This study investigates the behavioral and molecular effects of tPA gain-of-function in a social stress paradigm in male C57BL/6 mice using lentiviral vectors. Behaviorally, hippocampal tPA gain-of-function mitigated depression-like responses in the novelty-suppressed feeding, sucrose splash, tail suspension, and forced swim tests following exposure to chronic social stress. Additionally, in a two-bottle choice drinking paradigm, tPA overexpression reduced social stress-induced ethanol intake and preference, suggesting a role in dampening maladaptive coping behaviors. However, analysis of tastants’ intake and preference revealed no significant effects of tPA overexpression, indicating that it does not influence hedonic responses under stress conditions. Molecularly, tPA overexpression preserved hippocampal tPA mRNA expression and maintained levels of mature brain-derived neurotrophic factor in the hippocampus despite chronic stress exposure. These findings highlight the potential neuroprotective effects of tPA in maintaining hippocampal plasticity and mitigating stress-induced dysregulation of critical neurotrophic pathways. Collectively, this study underscores the potential of tPA as a therapeutic target for stress-induced mood and substance use disorders by modulating behavioral and neurobiological responses to chronic social stress.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"125 ","pages":"Pages 1-15"},"PeriodicalIF":2.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The impact of parental alcohol exposure on subsequent generations recently gained significant attention. Ethanol, widely consumed by humans, is known for its anxiolytic effects upon initial use. However, repeated ethanol consumption leads to cognitive dysfunction, dependence, and other physical abnormalities. In line with recent publications from our group, this study investigated the role of parental ethanol exposure—10 days prior to gestation—on learning and memory, which are critical cognitive abilities, in male and female offspring.
Adult male and female Wistar rats (n = 12) were exposed to ethanol (in drinking water) for 30 days, followed by a 10-day ethanol-free period. Each rat was then paired to mate with either an ethanol-naïve (control, n = 12) or ethanol-exposed rat, resulting in four distinct groups: (1) control male and female, (2) ethanol-exposed male and control female (P.EE), (3) ethanol-exposed female and control male (M.EE), and (4) ethanol-exposed male and female (P + M.EE). Adult male and female offspring were tested for spatial learning and memory (Morris Water Maze) and passive avoidance memory. Additionally, brain-derived neurotrophic factor (BDNF) levels in the cerebrospinal fluid were evaluated.
Results showed that spatial memory was negatively affected by parental ethanol consumption in both male and female offspring, while spatial learning was impaired only in female offspring of ethanol-exposed dams. In the passive avoidance paradigm, memory retrieval was impaired in ethanol-exposed male offspring, whereas in females, only the P + M.EE group showed a deficit in memory retention. While BDNF levels decreased in male offspring, an enhancement in BDNF was observed in female offspring of the P. EE group.
In conclusion, our findings suggest that parental ethanol exposure before conception has differential impacts on learning and memory, depending on the offspring's sex and the type of memory tested. Spatial memory was affected in both sexes (except for females in the P. EE group), while memory retrieval in the passive avoidance task remained unaffected in female offspring of the P. EE and M. EE groups. Conversely, male offspring of ethanol-exposed sires and dams exhibited deficits in passive avoidance memory. This may suggest that in memory tasks involving inhibitory cues, such as passive avoidance, female offspring of ethanol-exposed dams or sires are more resilient to memory deficits compared to male offspring. This resilience could possibly be attributed to their higher anxiety levels relative to males.
{"title":"Impact of parental ethanol exposure on offspring memory: Sex differences in spatial and passive avoidance tasks","authors":"Amirhossein Heidari , Arman Hajikarim-Hamedani , MohammadBasir Asefi , Haniyeh Soltani , Mohammad Saber Zamani , Yekta Ghane , Setareh Rassa , Mitra Sadat-Shirazi , Mohammad-Reza Zarrindast","doi":"10.1016/j.alcohol.2025.01.009","DOIUrl":"10.1016/j.alcohol.2025.01.009","url":null,"abstract":"<div><div>The impact of parental alcohol exposure on subsequent generations recently gained significant attention. Ethanol, widely consumed by humans, is known for its anxiolytic effects upon initial use. However, repeated ethanol consumption leads to cognitive dysfunction, dependence, and other physical abnormalities. In line with recent publications from our group, this study investigated the role of parental ethanol exposure—10 days prior to gestation—on learning and memory, which are critical cognitive abilities, in male and female offspring.</div><div>Adult male and female Wistar rats (n = 12) were exposed to ethanol (in drinking water) for 30 days, followed by a 10-day ethanol-free period. Each rat was then paired to mate with either an ethanol-naïve (control, n = 12) or ethanol-exposed rat, resulting in four distinct groups: (1) control male and female, (2) ethanol-exposed male and control female (P.EE), (3) ethanol-exposed female and control male (M.EE), and (4) ethanol-exposed male and female (P + M.EE). Adult male and female offspring were tested for spatial learning and memory (Morris Water Maze) and passive avoidance memory. Additionally, brain-derived neurotrophic factor (BDNF) levels in the cerebrospinal fluid were evaluated.</div><div>Results showed that spatial memory was negatively affected by parental ethanol consumption in both male and female offspring, while spatial learning was impaired only in female offspring of ethanol-exposed dams. In the passive avoidance paradigm, memory retrieval was impaired in ethanol-exposed male offspring, whereas in females, only the P + M.EE group showed a deficit in memory retention. While BDNF levels decreased in male offspring, an enhancement in BDNF was observed in female offspring of the P. EE group.</div><div>In conclusion, our findings suggest that parental ethanol exposure before conception has differential impacts on learning and memory, depending on the offspring's sex and the type of memory tested. Spatial memory was affected in both sexes (except for females in the P. EE group), while memory retrieval in the passive avoidance task remained unaffected in female offspring of the P. EE and M. EE groups. Conversely, male offspring of ethanol-exposed sires and dams exhibited deficits in passive avoidance memory. This may suggest that in memory tasks involving inhibitory cues, such as passive avoidance, female offspring of ethanol-exposed dams or sires are more resilient to memory deficits compared to male offspring. This resilience could possibly be attributed to their higher anxiety levels relative to males.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"124 ","pages":"Pages 13-21"},"PeriodicalIF":2.5,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.alcohol.2024.12.001
Suthat Liangpunsakul , Lorenzo Leggio
{"title":"FGF21 responses to alcohol, an insight from a comparative study in individuals with alcohol use disorder","authors":"Suthat Liangpunsakul , Lorenzo Leggio","doi":"10.1016/j.alcohol.2024.12.001","DOIUrl":"10.1016/j.alcohol.2024.12.001","url":null,"abstract":"","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"122 ","pages":"Pages 11-13"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.alcohol.2024.12.004
Vernon Garcia-Rivas , Alexa R. Soares , Merrilee A. Thomas , Jessica J. Na , Asia Smith , Marina R. Picciotto , Yann S. Mineur
Stress is a major contributing factor to binge drinking and development of alcohol use disorders (AUD), particularly in women. Both stress and chronic ethanol can enhance neuroinflammatory processes, which may dysregulate limbic circuits involved in ethanol reinforcement. Clinical and preclinical studies have identified sex differences in alcohol intake in response to neuroinflammatory triggers. Since both cyclic AMP (cAMP) signaling and microglial activation contribute to neuroinflammation, we explored their contribution to stress-induced ethanol drinking in mice. To this end, we first trained C57BL/6J male and female mice to volitionally drink ethanol through a modified version of the “Drinking-in-the-Dark” paradigm. We then assessed whether exposure to foot shock stress followed by repeated exposure to the previously stress-paired context might alter volitional ethanol drinking. We observed that stress exposure resulted in a delayed increase in ethanol intake, but only in female mice. The anti-inflammatory drug Apremilast, an inhibitor of phosphodiesterase type 4 (PDE4; the primary enzyme for cAMP degradation in the brain), reduced ethanol intake and decreased preference for ethanol regardless of stress exposure in females. In contrast, a partial pharmacological depletion of microglia via PLX3397 treatment did not significantly alter baseline ethanol drinking or stress-induced ethanol drinking in female mice. This study shows that female mice are more susceptible to stress-induced ethanol drinking than males, and that this occurs even after partial microglial depletion. In addition, modulation of cAMP signaling by Apremilast administration reduced ethanol drinking regardless of stress exposure, supporting the idea that it might be useful for treatment of AUD.
{"title":"Alcohol drinking is attenuated by PDE4 inhibition but partial microglia depletion is not sufficient to block stress-induced escalation of alcohol intake in female mice","authors":"Vernon Garcia-Rivas , Alexa R. Soares , Merrilee A. Thomas , Jessica J. Na , Asia Smith , Marina R. Picciotto , Yann S. Mineur","doi":"10.1016/j.alcohol.2024.12.004","DOIUrl":"10.1016/j.alcohol.2024.12.004","url":null,"abstract":"<div><div>Stress is a major contributing factor to binge drinking and development of alcohol use disorders (AUD), particularly in women. Both stress and chronic ethanol can enhance neuroinflammatory processes, which may dysregulate limbic circuits involved in ethanol reinforcement. Clinical and preclinical studies have identified sex differences in alcohol intake in response to neuroinflammatory triggers. Since both cyclic AMP (cAMP) signaling and microglial activation contribute to neuroinflammation, we explored their contribution to stress-induced ethanol drinking in mice. To this end, we first trained C57BL/6J male and female mice to volitionally drink ethanol through a modified version of the “Drinking-in-the-Dark” paradigm. We then assessed whether exposure to foot shock stress followed by repeated exposure to the previously stress-paired context might alter volitional ethanol drinking. We observed that stress exposure resulted in a delayed increase in ethanol intake, but only in female mice. The anti-inflammatory drug Apremilast, an inhibitor of phosphodiesterase type 4 (PDE4; the primary enzyme for cAMP degradation in the brain), reduced ethanol intake and decreased preference for ethanol regardless of stress exposure in females. In contrast, a partial pharmacological depletion of microglia via PLX3397 treatment did not significantly alter baseline ethanol drinking or stress-induced ethanol drinking in female mice. This study shows that female mice are more susceptible to stress-induced ethanol drinking than males, and that this occurs even after partial microglial depletion. In addition, modulation of cAMP signaling by Apremilast administration reduced ethanol drinking regardless of stress exposure, supporting the idea that it might be useful for treatment of AUD.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"122 ","pages":"Pages 31-42"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.alcohol.2024.10.002
C.S. Wilkinson , C.G. Modrak , T.D. Thompson , R.C. Conrad , I. Leon , L.A. Knackstedt
Alcohol and opioid polysubstance use (PSU) is common and often accompanied by higher trait anxiety. Oxytocin decreases anxiety, alcohol- and opioid-seeking and -taking but has not been assessed in the context of PSU. Here we developed a rat model of sequential oxycodone and alcohol PSU to examine the relationship between anxiety, alcohol and oxycodone intake, and the efficacy of systemic oxytocin to attenuate alcohol intake. Male and female Sprague–Dawley rats were assessed for baseline anxiety-like behavior using acoustic startle and the elevated plus maze (EPM). Rats were then given 2-bottle choice access to oxycodone and/or water for 6-hr/day for 7 days, followed by 2-bottle choice access to alcohol (20% v/v) and/or water for five 24-hr sessions across 10 days. Next, monosubstance (oxycodone- or alcohol-alone) rats continued to have access to only one substance/day while PSU rats had access to oxycodone and water for 3-hr, followed by alcohol and water for 6-hr. After 12 days, rats were tested in the EPM 20 h after alcohol access to examine withdrawal-related anxiety. Next, oxytocin (0, 0.3 or 1.0 mg/kg IP) was administered following the oxycodone/water session, 30 min prior to alcohol access. Rats received intragastric oxycodone (2 mg/kg) or water followed by intragastric alcohol (2 g/kg) and blood was collected to determine blood alcohol levels. Elevated baseline anxiety-like behavior was accompanied by reduced alcohol intake. Consumption of oxycodone did not alter alcohol intake but resulted in less anxiety-like behavior during withdrawal and prevented oxytocin from attenuating alcohol intake. Oxytocin (1 mg/kg) reduced alcohol intake in the alcohol-only condition, an effect that persisted for days after a single oxytocin administration. Rats that received oxycodone prior to non-contingent alcohol displayed higher blood alcohol levels than those that did not. These results support the necessity for the testing of medications for substance use in rodent models of PSU.
{"title":"Consumption of oxycodone prevents oxytocin from attenuating alcohol intake in rats","authors":"C.S. Wilkinson , C.G. Modrak , T.D. Thompson , R.C. Conrad , I. Leon , L.A. Knackstedt","doi":"10.1016/j.alcohol.2024.10.002","DOIUrl":"10.1016/j.alcohol.2024.10.002","url":null,"abstract":"<div><div>Alcohol and opioid polysubstance use (PSU) is common and often accompanied by higher trait anxiety. Oxytocin decreases anxiety, alcohol- and opioid-seeking and -taking but has not been assessed in the context of PSU. Here we developed a rat model of sequential oxycodone and alcohol PSU to examine the relationship between anxiety, alcohol and oxycodone intake, and the efficacy of systemic oxytocin to attenuate alcohol intake. Male and female Sprague–Dawley rats were assessed for baseline anxiety-like behavior using acoustic startle and the elevated plus maze (EPM). Rats were then given 2-bottle choice access to oxycodone and/or water for 6-hr/day for 7 days, followed by 2-bottle choice access to alcohol (20% v/v) and/or water for five 24-hr sessions across 10 days. Next, monosubstance (oxycodone- or alcohol-alone) rats continued to have access to only one substance/day while PSU rats had access to oxycodone and water for 3-hr, followed by alcohol and water for 6-hr. After 12 days, rats were tested in the EPM 20 h after alcohol access to examine withdrawal-related anxiety. Next, oxytocin (0, 0.3 or 1.0 mg/kg IP) was administered following the oxycodone/water session, 30 min prior to alcohol access. Rats received intragastric oxycodone (2 mg/kg) or water followed by intragastric alcohol (2 g/kg) and blood was collected to determine blood alcohol levels. Elevated baseline anxiety-like behavior was accompanied by reduced alcohol intake. Consumption of oxycodone did not alter alcohol intake but resulted in less anxiety-like behavior during withdrawal and prevented oxytocin from attenuating alcohol intake. Oxytocin (1 mg/kg) reduced alcohol intake in the alcohol-only condition, an effect that persisted for days after a single oxytocin administration. Rats that received oxycodone prior to non-contingent alcohol displayed higher blood alcohol levels than those that did not. These results support the necessity for the testing of medications for substance use in rodent models of PSU.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"122 ","pages":"Pages 43-53"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.alcohol.2024.01.003
Palaniswamy Ramaswamy , Athira S V , Pratibha Misra , V.S. Chauhan , Arka Adhvaryu , Anurodh Gupta , Ankita G , Sibin M K
Background
MicroRNAs are abundant in serum and have emerged as important regulators of gene expression, implicating them in a wide range of diseases. The purpose of this study was to discover and validate serum miRNAs in prediabetes associated with alcohol dependence syndrome (ADS).
Method
Serum samples from ADS patients with or without prediabetes and normoglycemic controls were subjected to microarray. Validation of identified candidate miRNAs was performed by RT-qPCR. Additionally, GO and KEGG pathway analyses were carried out to uncover target genes anticipated to be controlled by the candidate miRNAs.
Results
Notably, 198, and 172 miRNAs were differentially expressed in ADS-patients with or without prediabetes compared to healthy controls, and 7 miRNAs in ADS-patients with prediabetes compared to ADS-normoglycemic patients, respectively. Furthermore, hsa-miR-320b and hsa-miR-3135b were differentially expressed exclusively in ADS-patients with prediabetes, and this was further validated. Interestingly, GO and KEGG pathway analysis revealed that genes predicted to be modulated by the candidates were considerably enriched in numerous diabetes-related biological processes and pathways.
Conclusion
Our findings revealed that ADS-patients with or without prediabetes have different sets of miRNAs compared to normoglycemic healthy subjects. We propose serum hsa-miR-320b and hsa-miR-3135b as potential biomarkers for the diagnosis of prediabetes in ADS-patients.
{"title":"Circulating microRNA profiling identifies microRNAs linked to prediabetes associated with alcohol dependence syndrome","authors":"Palaniswamy Ramaswamy , Athira S V , Pratibha Misra , V.S. Chauhan , Arka Adhvaryu , Anurodh Gupta , Ankita G , Sibin M K","doi":"10.1016/j.alcohol.2024.01.003","DOIUrl":"10.1016/j.alcohol.2024.01.003","url":null,"abstract":"<div><h3>Background</h3><div>MicroRNAs are abundant in serum and have emerged as important regulators of gene expression, implicating them in a wide range of diseases. The purpose of this study was to discover and validate serum miRNAs in prediabetes associated with alcohol dependence syndrome (ADS).</div></div><div><h3>Method</h3><div>Serum samples from ADS patients with or without prediabetes and normoglycemic controls were subjected to microarray. Validation of identified candidate miRNAs was performed by RT-qPCR. Additionally, GO and KEGG pathway analyses were carried out to uncover target genes anticipated to be controlled by the candidate miRNAs.</div></div><div><h3>Results</h3><div>Notably, 198, and 172 miRNAs were differentially expressed in ADS-patients with or without prediabetes compared to healthy controls, and 7 miRNAs in ADS-patients with prediabetes compared to ADS-normoglycemic patients, respectively. Furthermore, hsa-miR-320b and hsa-miR-3135b were differentially expressed exclusively in ADS-patients with prediabetes, and this was further validated. Interestingly, GO and KEGG pathway analysis revealed that genes predicted to be modulated by the candidates were considerably enriched in numerous diabetes-related biological processes and pathways.</div></div><div><h3>Conclusion</h3><div>Our findings revealed that ADS-patients with or without prediabetes have different sets of miRNAs compared to normoglycemic healthy subjects. We propose serum hsa-miR-320b and hsa-miR-3135b as potential biomarkers for the diagnosis of prediabetes in ADS-patients.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"122 ","pages":"Pages 101-109"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.alcohol.2024.07.009
Benneth Ben-Azu , Pere-Ebi Y. Toloyai , Adaeze Adebesin , Vivian O. Ojiokor , Olusegun G. Adebayo , Aliance Romain Fokoua , Goodes E. Moke , Elo J. Ejukolemu , Ife-Oluwa O. Akpojevughe , Abdulkareem M. Abdulkadir , Ephraim Okwuchi
Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are very prevalent and co-occurring. It is unclear how alcohol exacerbates PTSD predicaments owing to less characterized pathophysiological mechanisms. Also, studies on pharmacological agents that can effectively reverse PTSD-AUD comorbidity have, to date, been scarce. Hence, we designed a methodological approach to investigate the pathophysiological mechanisms and pharmacological outcomes of morin, a neuroprotective flavonoid in mice. After 7 days of PTSD following single-prolonged stress (SPS) induction in mice, the PTSD mice were exposed to intermittent binge ethanol administration using ethanol (2 g/kg, oral gavage) every other day, alongside daily morin (50 and 100 mg/kg) or fluoxetine (10 mg/kg) from days 8–21. The consequences of PTSD-AUD behavior, hypothalamic-pituitary-adrenal-axis (HPA-axis) dysfunction, neurochemistry, oxidative/nitrergic stress, and inflammation were evaluated in the prefrontal cortex (PFC), striatum, and hippocampus of mice. The exacerbated anxiety-like behavior, and spatial/non-spatial memory deficits, with general depressive phenotypes and social stress susceptibility by SPS-ethanol interaction, were alleviated by morin and fluoxetine, evidenced by reduced corticosterone release and adrenal hypertrophy. SPS-ethanol exacerbates dopamine, serotonin, and glutamic acid decarboxylase alterations, and monoamine oxidase-B and acetylcholinesterase hyperactivities in the striatum, PFC, and hippocampus, respectively, which were prevented by morin. Compared to SPS-ethanol aggravation, morin reduced TNF-α and IL-6 release, malondialdehyde and nitrite levels, with improved antioxidant (glutathione, superoxide-dismutase, catalase) levels in the hippocampus, PFC, and striatum. Overall, these findings suggest that AUD-exacerbated PTSD might be primarily connected, among other mechanisms, with aggravated HPA-axis dysfunction, upregulated neurochemical degradative enzymes, enhancement of oxidative/nitrergic stress and neuroinflammation, and stereo-selectively in the mice brains, which morin abated via the preventive mechanisms.
{"title":"Alcohol exacerbates post-traumatic stress psychiatric behavior and its neuropathological sequalae in experimental mice: preventive effects of morin","authors":"Benneth Ben-Azu , Pere-Ebi Y. Toloyai , Adaeze Adebesin , Vivian O. Ojiokor , Olusegun G. Adebayo , Aliance Romain Fokoua , Goodes E. Moke , Elo J. Ejukolemu , Ife-Oluwa O. Akpojevughe , Abdulkareem M. Abdulkadir , Ephraim Okwuchi","doi":"10.1016/j.alcohol.2024.07.009","DOIUrl":"10.1016/j.alcohol.2024.07.009","url":null,"abstract":"<div><div>Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are very prevalent and co-occurring. It is unclear how alcohol exacerbates PTSD predicaments owing to less characterized pathophysiological mechanisms. Also, studies on pharmacological agents that can effectively reverse PTSD-AUD comorbidity have, to date, been scarce. Hence, we designed a methodological approach to investigate the pathophysiological mechanisms and pharmacological outcomes of morin, a neuroprotective flavonoid in mice. After 7 days of PTSD following single-prolonged stress (SPS) induction in mice, the PTSD mice were exposed to intermittent binge ethanol administration using ethanol (2 g/kg, oral gavage) every other day, alongside daily morin (50 and 100 mg/kg) or fluoxetine (10 mg/kg) from days 8–21. The consequences of PTSD-AUD behavior, hypothalamic-pituitary-adrenal-axis (HPA-axis) dysfunction, neurochemistry, oxidative/nitrergic stress, and inflammation were evaluated in the prefrontal cortex (PFC), striatum, and hippocampus of mice. The exacerbated anxiety-like behavior, and spatial/non-spatial memory deficits, with general depressive phenotypes and social stress susceptibility by SPS-ethanol interaction, were alleviated by morin and fluoxetine, evidenced by reduced corticosterone release and adrenal hypertrophy. SPS-ethanol exacerbates dopamine, serotonin, and glutamic acid decarboxylase alterations, and monoamine oxidase-B and acetylcholinesterase hyperactivities in the striatum, PFC, and hippocampus, respectively, which were prevented by morin. Compared to SPS-ethanol aggravation, morin reduced TNF-α and IL-6 release, malondialdehyde and nitrite levels, with improved antioxidant (glutathione, superoxide-dismutase, catalase) levels in the hippocampus, PFC, and striatum. Overall, these findings suggest that AUD-exacerbated PTSD might be primarily connected, among other mechanisms, with aggravated HPA-axis dysfunction, upregulated neurochemical degradative enzymes, enhancement of oxidative/nitrergic stress and neuroinflammation, and stereo-selectively in the mice brains, which morin abated via the preventive mechanisms.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"122 ","pages":"Pages 15-29"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.alcohol.2024.10.046
Dokyoung S. You , Maisa S. Ziadni , Noel Vest , Nareh Megerdichian , Tara Maronesy , Ralph J. Castro , Beth D. Darnall , Sean C. Mackey , Keith Humphreys
Introduction
To combat high-risk alcohol consumption, we introduced a 30-day alcohol abstinence challenge targeted at heavy drinkers with and without chronic pain. Our study aimed to assess the challenge's feasibility and safety and to explore its perceived benefits. Our exploratory aim was to identify participants' coping strategies during the challenge.
Methods
Our single-arm study recruited heavy drinkers from a pain clinic and a university setting (n = 34, 64.7% chronic pain). Participants underwent a modified community-based 30-day challenge, which included motivational interviewing, an individualized start date, and weekly phone check-ins.
Results
We found the 30-day challenge was feasible and safe; 72.3% of eligible heavy drinkers participated in the challenge with no serious adverse events. Most challengers (94.1%) reported some benefit from the challenge, which included improvements in alcohol withdrawal symptoms, sleep, and alcohol abstinence self-efficacy, but not in pain. We identified 25 perceived benefits and 21 coping strategies.
Conclusion
Our study confirms that a 30-day alcohol abstinence challenge is a feasible and safe intervention for heavy drinkers with and without chronic pain, yielding notable health benefits. The challenge also facilitated the development of effective coping strategies. Future studies should explore the long-term benefits of such interventions in broader outpatient settings.
{"title":"Evaluating a 30-day alcohol abstinence challenge in heavy-drinking individuals with and without chronic pain: Feasibility, safety, and perceived benefits","authors":"Dokyoung S. You , Maisa S. Ziadni , Noel Vest , Nareh Megerdichian , Tara Maronesy , Ralph J. Castro , Beth D. Darnall , Sean C. Mackey , Keith Humphreys","doi":"10.1016/j.alcohol.2024.10.046","DOIUrl":"10.1016/j.alcohol.2024.10.046","url":null,"abstract":"<div><h3>Introduction</h3><div>To combat high-risk alcohol consumption, we introduced a 30-day alcohol abstinence challenge targeted at heavy drinkers with and without chronic pain. Our study aimed to assess the challenge's feasibility and safety and to explore its perceived benefits. Our exploratory aim was to identify participants' coping strategies during the challenge.</div></div><div><h3>Methods</h3><div>Our single-arm study recruited heavy drinkers from a pain clinic and a university setting (n = 34, 64.7% chronic pain). Participants underwent a modified community-based 30-day challenge, which included motivational interviewing, an individualized start date, and weekly phone check-ins.</div></div><div><h3>Results</h3><div>We found the 30-day challenge was feasible and safe; 72.3% of eligible heavy drinkers participated in the challenge with no serious adverse events. Most challengers (94.1%) reported some benefit from the challenge, which included improvements in alcohol withdrawal symptoms, sleep, and alcohol abstinence self-efficacy, but not in pain. We identified 25 perceived benefits and 21 coping strategies.</div></div><div><h3>Conclusion</h3><div>Our study confirms that a 30-day alcohol abstinence challenge is a feasible and safe intervention for heavy drinkers with and without chronic pain, yielding notable health benefits. The challenge also facilitated the development of effective coping strategies. Future studies should explore the long-term benefits of such interventions in broader outpatient settings.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"122 ","pages":"Pages 91-100"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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