Pub Date : 2023-09-14DOI: 10.1016/j.pbb.2023.173635
Patricia E. Bunney , John R. Smethells , Mark G. LeSage
Despite considerable evidence suggesting that sweet foods are a substitute for nicotine in humans, no formal behavioral economic analysis of this interrelationship has been conducted in nonhumans. The purpose of the present study was to examine this phenomenon in rats using concurrent schedules of sucrose pellet, chow pellet, and nicotine reinforcer delivery. Rats responded on separate levers that delivered sucrose pellets, chow pellets, or nicotine infusions under concurrent fixed-ratio (FR) 1 schedules for each commodity within a closed economy. Following stable food and nicotine intake, the unit price of either sucrose or nicotine (the primary commodity) was increased while the two alternative commodities remained unchanged. Substitution was quantified using a behavioral economic cross-price model, as well as a novel commodity relation index that normalizes consumption of dissimilar commodities. Asymmetrical partial substitution was observed, wherein sucrose served as a partial substitute for nicotine, but nicotine failed to substitute for sucrose. Moreover, sucrose was a stronger partial substitute for nicotine than chow in most rats. These findings indicate that substitution of food for nicotine depends on the type of food. These findings mirror the selective increase in carbohydrate intake that can occur during smoking cessation and demonstrate a behavioral economic mechanism that may mediate it.
{"title":"Substitutability of nicotine and sucrose in rats: A behavioral economic analysis","authors":"Patricia E. Bunney , John R. Smethells , Mark G. LeSage","doi":"10.1016/j.pbb.2023.173635","DOIUrl":"10.1016/j.pbb.2023.173635","url":null,"abstract":"<div><p><span>Despite considerable evidence suggesting that sweet foods are a substitute for nicotine in humans, no formal behavioral economic analysis of this interrelationship has been conducted in nonhumans. The purpose of the present study was to examine this phenomenon in rats using concurrent schedules of sucrose pellet, chow pellet, and nicotine reinforcer delivery. Rats responded on separate levers that delivered sucrose pellets, chow pellets, or nicotine infusions under concurrent fixed-ratio (FR) 1 schedules for each commodity within a closed economy. Following stable food and nicotine intake, the unit price of either sucrose or nicotine (the primary commodity) was increased while the two alternative commodities remained unchanged. Substitution was quantified using a behavioral economic cross-price model, as well as a novel commodity relation index that normalizes consumption of dissimilar commodities. Asymmetrical partial substitution was observed, wherein sucrose served as a partial substitute for nicotine, but nicotine failed to substitute for sucrose. Moreover, sucrose was a stronger partial substitute for nicotine than chow in most rats. These findings indicate that substitution of food for nicotine depends on the type of food. These findings mirror the selective increase in carbohydrate intake that can occur during </span>smoking cessation and demonstrate a behavioral economic mechanism that may mediate it.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"232 ","pages":"Article 173635"},"PeriodicalIF":3.6,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10263587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.pbb.2023.173607
Nina-Francecsa Parrella , Aron Thomas Hill , Peter Gregory Enticott , Pamela Barhoun , Isabella Simone Bower , Talitha Caitlyn Ford
Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications. These phyto-cannabinoids have multiple biological targets, including the body's endocannabinoid system. There is growing scientific interest in the use of CBD, a non-intoxicating compound, to ameliorate symptoms associated with neurodevelopmental disorders. However, its suitability as a pharmaceutical intervention has not been reliably established in these clinical populations.
This systematic review examines the nine published randomised controlled trials (RCTs) that have probed the safety and efficacy of CBD in individuals diagnosed with attention deficit hyperactivity disorder, autism spectrum disorder, intellectual disability, Tourette Syndrome, and complex motor disorders. Studies were identified systematically through searching four databases: Medline, CINAHL complete, PsycINFO, and EMBASE.
Inclusion criteria were randomised controlled trials involving CBD and participants with neurodevelopmental disorders. No publication year or language restrictions were applied. Relevant data were extracted from the identified list of eligible articles. After extraction, data were cross-checked between the authors to ensure consistency.
Several trials indicate potential efficacy, although this possibility is currently too inconsistent across RCTs to confidently guide clinical usage. Study characteristics, treatment properties, and outcomes varied greatly across the included trials. The material lack of comparable RCTs leaves CBD's suitability as a pharmacological treatment for neurodevelopmental disorders largely undetermined. A stronger evidence base is urgently required to establish safety and efficacy profiles and guide the ever-expanding clinical uptake of cannabis-derived compounds in neurodevelopmental disorders.
{"title":"A systematic review of cannabidiol trials in neurodevelopmental disorders","authors":"Nina-Francecsa Parrella , Aron Thomas Hill , Peter Gregory Enticott , Pamela Barhoun , Isabella Simone Bower , Talitha Caitlyn Ford","doi":"10.1016/j.pbb.2023.173607","DOIUrl":"10.1016/j.pbb.2023.173607","url":null,"abstract":"<div><p>Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications. These phyto-cannabinoids have multiple biological targets, including the body's endocannabinoid system. There is growing scientific interest in the use of CBD, a non-intoxicating compound, to ameliorate symptoms associated with neurodevelopmental disorders. However, its suitability as a pharmaceutical intervention has not been reliably established in these clinical populations.</p><p>This systematic review examines the nine published randomised controlled trials (RCTs) that have probed the safety and efficacy of CBD in individuals diagnosed with attention deficit hyperactivity disorder, autism spectrum disorder, intellectual disability, Tourette Syndrome, and complex motor disorders. Studies were identified systematically through searching four databases: Medline, CINAHL complete, PsycINFO, and EMBASE.</p><p>Inclusion criteria were randomised controlled trials involving CBD and participants with neurodevelopmental disorders. No publication year or language restrictions were applied. Relevant data were extracted from the identified list of eligible articles. After extraction, data were cross-checked between the authors to ensure consistency.</p><p>Several trials indicate potential efficacy, although this possibility is currently too inconsistent across RCTs to confidently guide clinical usage. Study characteristics, treatment properties, and outcomes varied greatly across the included trials. The material lack of comparable RCTs leaves CBD's suitability as a pharmacological treatment for neurodevelopmental disorders largely undetermined. A stronger evidence base is urgently required to establish safety and efficacy profiles and guide the ever-expanding clinical uptake of cannabis-derived compounds in neurodevelopmental disorders.</p><p>Prospero registration number: CRD42021267839.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"230 ","pages":"Article 173607"},"PeriodicalIF":3.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10141221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Depression is a common psychiatric disorder affecting around 300 million people worldwide. Serum cortisol and glucocorticoid levels in humans are reportedly higher in patients with depression compared to controls. Furthermore, rodents repeatedly treated with exogenous corticosterone (CORT), a glucocorticoid in rodents, exhibit deficits in emotional behaviors. To confirm the availability of mice with chronic CORT treatment as an animal model of depression, we investigated the effect of chronic CORT treatment on depression-like behavioral and neuropathological phenotypes in C57BL/6N male mice. Behavioral studies showed depression- and anxiety-like behaviors in mice treated with CORT compared with control mice in the forced-swim and elevated-plus maze tests. Additionally, treated mice represented anhedonia and social behavior impairments in the sucrose preference and social interaction tests, respectively. Brains of depression patients have altered expression of reelin, an extracellular matrix protein involved in neuronal development and function. Likewise, in the present study, mice with chronic CORT treatment also exhibited reelin downregulation in cells of the hippocampus. Hence, we investigated therapeutic effects of reelin supplementation on CORT-induced behavioral abnormalities in mice. Microinjections of recombinant reelin protein into the hippocampus did not rescue behavioral deficits in mice with chronic CORT treatment. These results suggest that C57BL/6N male mice chronically treated with CORT are a suitable animal depression model, in which depressive behaviors may occur independently of the alternation of hippocampal Reelin expression.
{"title":"Emotional behaviors as well as the hippocampal reelin expression in C57BL/6N male mice chronically treated with corticosterone","authors":"Daisuke Ibi , Genki Nakasai , Masahito Sawahata , Rika Takaba , Maho Kinoshita , Kiyofumi Yamada , Masayuki Hiramatsu","doi":"10.1016/j.pbb.2023.173617","DOIUrl":"10.1016/j.pbb.2023.173617","url":null,"abstract":"<div><p><span><span>Depression is a common psychiatric disorder affecting around 300 million people worldwide. Serum cortisol<span> and glucocorticoid levels in humans are reportedly higher in patients with depression compared to controls. Furthermore, rodents repeatedly treated with exogenous </span></span>corticosterone<span><span> (CORT), a glucocorticoid in rodents, exhibit deficits in emotional behaviors. To confirm the availability of mice with chronic CORT treatment as an </span>animal model<span><span><span> of depression, we investigated the effect of chronic CORT treatment on depression-like behavioral and neuropathological phenotypes in C57BL/6N male mice. Behavioral studies showed depression- and anxiety-like behaviors in mice treated with CORT compared with control mice in the forced-swim and elevated-plus maze tests. Additionally, treated mice represented anhedonia<span> and social behavior impairments in the sucrose preference and </span></span>social interaction tests, respectively. Brains of depression patients have altered expression of </span>reelin<span>, an extracellular matrix protein<span> involved in neuronal development and function. Likewise, in the present study, mice with chronic CORT treatment also exhibited reelin downregulation in cells of the hippocampus. Hence, we investigated therapeutic effects of reelin supplementation on CORT-induced behavioral abnormalities in mice. </span></span></span></span></span>Microinjections of recombinant reelin protein into the hippocampus did not rescue behavioral deficits in mice with chronic CORT treatment. These results suggest that C57BL/6N male mice chronically treated with CORT are a suitable animal depression model, in which depressive behaviors may occur independently of the alternation of hippocampal Reelin expression.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"230 ","pages":"Article 173617"},"PeriodicalIF":3.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10199444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.pbb.2023.173605
Mariel P. Seiglie , Lauren Lepeak , Sophia Miracle, Pietro Cottone, Valentina Sabino
Background
Anxiety disorders are the most prevalent psychiatric disorders, and they are highly comorbid with chronic pain conditions. The central nucleus of the amygdala (CeA) is known not only for its role in the regulation of anxiety but also as an important site for the negative affective dimension of pain. Pituitary adenylate cyclase activating polypeptide (PACAP), a neuropeptide whose terminals are abundant in the CeA, is strongly implicated in the stress response as well as in pain processing. Here, using Cre-dependent viral vectors, we explored in greater detail the role of the PACAP projection to the CeA that originates in the lateral parabrachial nucleus (LPB).
Methods
We first performed a circuit mapping experiment by injecting an anterograde Cre-dependent virus expressing a fluorescent reporter in the LPB of PACAP-Cre mice and observing their projections. Then, we used a chemogenetic approach (a Cre-dependent Designer Receptors Activated by Designer Drugs, DREADDs) to assess the effects of the direct stimulation of the PACAP LPB to CeA projection on general locomotor activity, anxiety-like behavior (using a defensive withdrawal test), and mechanical pain sensitivity (using the von Frey test).
Results
We found that the CeA, together with other areas, is one of the major downstream projection targets of PACAP neurons originating in the lateral parabrachial nucleus (LPB). In the DREADD experiment, we then found that the selective activation of this neuronal pathway is sufficient to increase both anxiety-like behavior and mechanical pain sensitivity in mice, without affecting general locomotor activity.
Conclusion
In conclusion, our data suggest that the dysregulation of this circuit may contribute to a variety of anxiety disorders and chronic pain states, and that PACAP may represent an important therapeutic target for the treatment of these conditions.
{"title":"Stimulation of lateral parabrachial (LPB) to central amygdala (CeA) pituitary adenylate cyclase-activating polypeptide (PACAP) neurons induces anxiety-like behavior and mechanical allodynia","authors":"Mariel P. Seiglie , Lauren Lepeak , Sophia Miracle, Pietro Cottone, Valentina Sabino","doi":"10.1016/j.pbb.2023.173605","DOIUrl":"10.1016/j.pbb.2023.173605","url":null,"abstract":"<div><h3>Background</h3><p><span><span>Anxiety disorders are the most prevalent psychiatric disorders, and they are highly comorbid with chronic pain conditions. The central nucleus of the amygdala (CeA) is known not only for its role in the regulation of anxiety but also as an important site for the negative affective dimension of pain. </span>Pituitary adenylate cyclase activating polypeptide (PACAP), a </span>neuropeptide<span><span> whose terminals are abundant in the CeA, is strongly implicated in the stress response as well as in pain processing. Here, using Cre-dependent viral vectors, we explored in greater detail the role of the PACAP projection to the CeA that originates in the </span>lateral parabrachial nucleus (LPB).</span></p></div><div><h3>Methods</h3><p>We first performed a circuit mapping experiment by injecting an anterograde Cre-dependent virus expressing a fluorescent reporter in the LPB of PACAP-Cre mice and observing their projections. Then, we used a chemogenetic<span> approach (a Cre-dependent Designer Receptors Activated by Designer Drugs, DREADDs) to assess the effects of the direct stimulation of the PACAP LPB to CeA projection on general locomotor activity, anxiety-like behavior<span> (using a defensive withdrawal test), and mechanical pain sensitivity (using the von Frey test).</span></span></p></div><div><h3>Results</h3><p>We found that the CeA, together with other areas, is one of the major downstream projection targets of PACAP neurons originating in the lateral parabrachial nucleus (LPB). In the DREADD experiment, we then found that the selective activation of this neuronal pathway is sufficient to increase both anxiety-like behavior and mechanical pain sensitivity in mice, without affecting general locomotor activity.</p></div><div><h3>Conclusion</h3><p>In conclusion, our data suggest that the dysregulation of this circuit may contribute to a variety of anxiety disorders and chronic pain states, and that PACAP may represent an important therapeutic target for the treatment of these conditions.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"230 ","pages":"Article 173605"},"PeriodicalIF":3.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10144128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.pbb.2023.173590
Yixue Qin , Haoxuan Li , Yuqi Zhang , Jun-Li Cao , Wenxin Zhang , Hongxing Zhang
Ketamine has been increasingly used as a rapid-onset antidepressant in specific clinical settings. However, as a psychedelic reagent, the potential of physical and psychological dependence limits its clinical use. Here, we added retigabine, a KCNQ channel opener, as an adjunctive treatment to observe its effect on ketamine's antidepressant property in a forced swim test in both male and female C57BL/6 J mice. Behavioral data demonstrated that intraperitoneal injection of ketamine exhibited a dose-dependent effect on animals' immobility performance in the forced swim test. Adding retigabine was sufficient to induce a remarkable antidepressant effect in mice treated with a relatively lower dose of ketamine which failed to be antidepressant when administrated separately. When simultaneously gave retigabine, ketamine's antidepressant effect in the forced swim test was significantly enhanced with a prolonged effective duration. Together, these results from both male and female mice indicated that adjunctive treatment with retigabine was an alternative to promote the antidepressant effect of ketamine, thus holding the possibility of encountering its possible physical and psychological dependence.
{"title":"Retigabine promotes ketamine's antidepressant effect in the forced swim test in male and female C57BL/6J mice","authors":"Yixue Qin , Haoxuan Li , Yuqi Zhang , Jun-Li Cao , Wenxin Zhang , Hongxing Zhang","doi":"10.1016/j.pbb.2023.173590","DOIUrl":"10.1016/j.pbb.2023.173590","url":null,"abstract":"<div><p><span><span>Ketamine<span> has been increasingly used as a rapid-onset antidepressant in specific clinical settings. However, as a psychedelic reagent, the potential of physical and psychological dependence limits its clinical use. Here, we added </span></span>retigabine<span>, a KCNQ channel<span> opener, as an adjunctive treatment to observe its effect on ketamine's antidepressant property in a forced swim test in both male and female C57BL/6 J mice. Behavioral data demonstrated that </span></span></span>intraperitoneal injection<span> of ketamine exhibited a dose-dependent effect on animals' immobility performance in the forced swim test. Adding retigabine was sufficient to induce a remarkable antidepressant effect in mice treated with a relatively lower dose of ketamine which failed to be antidepressant when administrated separately. When simultaneously gave retigabine, ketamine's antidepressant effect in the forced swim test was significantly enhanced with a prolonged effective duration. Together, these results from both male and female mice indicated that adjunctive treatment with retigabine was an alternative to promote the antidepressant effect of ketamine, thus holding the possibility of encountering its possible physical and psychological dependence.</span></p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"230 ","pages":"Article 173590"},"PeriodicalIF":3.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10142244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.pbb.2023.173606
Ziguo Lan , Ryosuke O. Tachibana , Kouta Kanno
Developmental factors for autism spectrum disorders (ASDs) have been an ongoing debate despite an increasing number of reports on genetic factors. Recent studies have suggested maternal intake of selective serotonin reuptake inhibitors (SSRIs) as a possible developmental factor elevating the risk for ASD in offspring. Here, we show that maternal exposure of mice to an SSRI, Fluoxetine (FLX), induces abnormal ultrasonic vocalizations (USVs), an indicator of ASD-related behavior. We tested the effect of FLX intake during pregnancy, lactation, or both. We found that the lactation and both conditions decreased the number of USVs emitted by offspring pups. An index for assessing the syllables' frequency modulation revealed that highly modulated syllables appeared to be inhibited only in both conditions. Furthermore, we found that the number of serotonergic neurons at adulthood was reduced in the progeny of mice treated with FLX in all conditions. In addition, maternal exposure to FLX through pregnancy and lactation induced a high death rate of early post-natal pups. These suggest that the maternal exposure to SSRIs affects early development of offsprings as well as the serotonergic system. Focusing on vocal communication, our results indicate that intake of an SSRI during lactation increases the risk of abnormal USVs in pups, and provides potential insights into the development of ASD.
{"title":"Chronic exposure of female mice to selective serotonin reuptake inhibitors during lactation induces vocal behavior deficits in pre-weaned offspring","authors":"Ziguo Lan , Ryosuke O. Tachibana , Kouta Kanno","doi":"10.1016/j.pbb.2023.173606","DOIUrl":"10.1016/j.pbb.2023.173606","url":null,"abstract":"<div><p><span><span>Developmental factors for autism spectrum disorders (ASDs) have been an ongoing debate despite an increasing number of reports on </span>genetic factors<span>. Recent studies have suggested maternal intake of selective serotonin reuptake inhibitors (SSRIs) as a possible developmental factor elevating the risk for ASD in offspring. Here, we show that maternal exposure of mice to an SSRI, </span></span>Fluoxetine<span><span><span> (FLX), induces abnormal ultrasonic vocalizations (USVs), an indicator of ASD-related </span>behavior<span>. We tested the effect of FLX intake during pregnancy, lactation, or both. We found that the lactation and both conditions decreased the number of USVs emitted by offspring pups. An index for assessing the syllables' frequency modulation revealed that highly modulated syllables appeared to be inhibited only in both conditions. Furthermore, we found that the number of </span></span>serotonergic neurons at adulthood was reduced in the progeny of mice treated with FLX in all conditions. In addition, maternal exposure to FLX through pregnancy and lactation induced a high death rate of early post-natal pups. These suggest that the maternal exposure to SSRIs affects early development of offsprings as well as the serotonergic system. Focusing on vocal communication, our results indicate that intake of an SSRI during lactation increases the risk of abnormal USVs in pups, and provides potential insights into the development of ASD.</span></p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"230 ","pages":"Article 173606"},"PeriodicalIF":3.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10146260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.pbb.2023.173616
Keith A. Trujillo
{"title":"Opiophobia and the tragedy of needless pain: A call for education and balance","authors":"Keith A. Trujillo","doi":"10.1016/j.pbb.2023.173616","DOIUrl":"10.1016/j.pbb.2023.173616","url":null,"abstract":"","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"230 ","pages":"Article 173616"},"PeriodicalIF":3.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10199952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.pbb.2023.173618
Jesús E. Yepez, Jorge Juárez
Substance dependence is a disorder that alters the functioning of the nervous system due to frequent abuse of drugs. The role of dopamine in the addictive effect of psychostimulants is well known; however, the involvement of the noradrenergic system is still unclear and poorly understood, though drugs like cocaine and amphetamines are known to exert significant activity on this system. The drug modafinil (MOD) has no proven addictive effect. It promotes wakefulness by acting mainly on the dopaminergic system and, to a lesser degree, the noradrenergic (NOR) system. Atomoxetine (ATX) is a non-stimulant drug that acts only on the NOR system, enhancing its activity. The aims of the present study were to analyze the effect of co-activating the DA and NOR systems (with MOD and ATX, respectively) on motor activity and exploratory behavior, and to examine the possible emergence of rewarding properties of MOD and an MOD+ATX mixture. Male Wistar rats at postnatal day 60 were treated chronically (16 days) with either monotherapy with 2ATX, 4ATX, or 60MOD mg/kg, two combinations of these substances –60MOD + 2ATX and 60MOD + 4ATX– or a vehicle. The rats co-administered with 60MOD + 4ATX reduced the rearing behavior frequency induced by MOD, but this behavior was sensitized by self-administration of the MOD+ATX mixture after chronic treatment. The rats pre-treated with 60MOD + 4ATX showed higher self-administration of MOD and greater activity on an operant task to obtain the MOD+ATX mixture. In addition, the 60MOD, 2ATX, and 60MOD + 2ATX groups showed sensitization of exploratory behavior after ingesting the mixture. Results suggest that the noradrenergic system enhances the incentive value of MOD and a MOD+ATX mixture, while also playing an important role in the sensitization of exploratory behavior.
{"title":"Atomoxetine promotes incentive value of modafinil and sensitizes exploratory behavior","authors":"Jesús E. Yepez, Jorge Juárez","doi":"10.1016/j.pbb.2023.173618","DOIUrl":"10.1016/j.pbb.2023.173618","url":null,"abstract":"<div><p><span><span>Substance dependence is a disorder that alters the functioning of the nervous system due to frequent abuse of drugs. The role of dopamine in the addictive effect of </span>psychostimulants<span> is well known; however, the involvement of the noradrenergic system is still unclear and poorly understood, though drugs like cocaine and amphetamines are known to exert significant activity on this system. The drug modafinil (MOD) has no proven addictive effect. It promotes wakefulness by acting mainly on the </span></span>dopaminergic<span> system and, to a lesser degree, the noradrenergic (NOR) system. Atomoxetine<span><span> (ATX) is a non-stimulant drug that acts only on the NOR system, enhancing its activity. The aims of the present study were to analyze the effect of co-activating the DA and NOR systems (with MOD and ATX, respectively) on motor activity and exploratory behavior, and to examine the possible emergence of rewarding properties of MOD and an MOD+ATX mixture. Male </span>Wistar rats<span> at postnatal day 60 were treated chronically (16 days) with either monotherapy with 2ATX, 4ATX, or 60MOD mg/kg, two combinations of these substances –60MOD + 2ATX and 60MOD + 4ATX– or a vehicle. The rats co-administered with 60MOD + 4ATX reduced the rearing behavior frequency induced by MOD, but this behavior was sensitized by self-administration of the MOD+ATX mixture after chronic treatment. The rats pre-treated with 60MOD + 4ATX showed higher self-administration of MOD and greater activity on an operant task to obtain the MOD+ATX mixture. In addition, the 60MOD, 2ATX, and 60MOD + 2ATX groups showed sensitization of exploratory behavior after ingesting the mixture. Results suggest that the noradrenergic system enhances the incentive value of MOD and a MOD+ATX mixture, while also playing an important role in the sensitization of exploratory behavior.</span></span></span></p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"230 ","pages":"Article 173618"},"PeriodicalIF":3.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10498206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.1016/j.pbb.2023.173601
Harrison J. Elder , D. Matthew Walentiny , Patrick M. Beardsley
Rationale
The opioid epidemic remains a pressing public health crisis in the United States. Most of these overdose deaths are a result of lethal respiratory depression. In recent years the increasing incidence of opioid-involved overdose deaths has been driven by fentanyl, which is more resistant to adequate reversal by naloxone (NARCAN ®) than semi-synthetic or classical morphinan predecessors like oxycodone and heroin. For this and other reasons (e.g., precipitating withdrawal) non-opioidergic pharmacotherapies to reverse opioid-depressed respiration are needed. Methylxanthines are a class of stimulant drugs including caffeine and theophylline which exert their effects primarily via adenosine receptor antagonism. Evidence suggests methylxanthines can stimulate respiration by enhancing neural activity in respiratory nuclei in the pons and medulla independent of opioid receptors. This study aimed to determine whether caffeine and theophylline can stimulate respiration in mice when depressed by fentanyl and oxycodone.
Methods
Whole-body plethysmography was used to characterize fentanyl and oxycodone's effects on respiration and their reversal by naloxone in male Swiss Webster mice. Next, caffeine and theophylline were tested for their effects on basal respiration. Finally, each methylxanthine was evaluated for its ability to reverse similar levels of respiratory depression induced by fentanyl or oxycodone.
Results and conclusions
Oxycodone and fentanyl dose-dependently reduced respiratory minute volume (ml/min; MVb) that was reversible by naloxone. Caffeine and theophylline each significantly increased basal MVb. Theophylline, but not caffeine, completely reversed oxycodone-depressed respiration. In contrast, neither methylxanthine elevated fentanyl-depressed respiration at the doses tested. Despite their limited efficacy for reversing opioid-depressed respiration when administered alone, the methylxanthines safety, duration, and mechanism of action supports further evaluation in combination with naloxone to augment its reversal of opioid-depressed respiration.
{"title":"Theophylline reverses oxycodone's but not fentanyl's respiratory depression in mice while caffeine is ineffective against both opioids","authors":"Harrison J. Elder , D. Matthew Walentiny , Patrick M. Beardsley","doi":"10.1016/j.pbb.2023.173601","DOIUrl":"10.1016/j.pbb.2023.173601","url":null,"abstract":"<div><h3>Rationale</h3><p><span><span><span>The opioid epidemic remains a pressing public health crisis in the United States. Most of these overdose deaths are a result of lethal respiratory depression. In recent years the increasing incidence of opioid-involved overdose deaths has been driven by </span>fentanyl<span>, which is more resistant to adequate reversal by naloxone (NARCAN ®) than semi-synthetic or classical </span></span>morphinan<span> predecessors like oxycodone<span><span> and heroin. For this and other reasons (e.g., precipitating withdrawal) non-opioidergic pharmacotherapies to reverse opioid-depressed respiration are needed. </span>Methylxanthines are a class of stimulant drugs including caffeine and </span></span></span>theophylline<span><span> which exert their effects primarily via adenosine receptor antagonism. Evidence suggests methylxanthines can stimulate respiration by enhancing neural activity in respiratory nuclei in the pons and medulla independent of </span>opioid receptors. This study aimed to determine whether caffeine and theophylline can stimulate respiration in mice when depressed by fentanyl and oxycodone.</span></p></div><div><h3>Methods</h3><p>Whole-body plethysmography was used to characterize fentanyl and oxycodone's effects on respiration and their reversal by naloxone in male Swiss Webster mice. Next, caffeine and theophylline were tested for their effects on basal respiration. Finally, each methylxanthine was evaluated for its ability to reverse similar levels of respiratory depression induced by fentanyl or oxycodone.</p></div><div><h3>Results and conclusions</h3><p>Oxycodone and fentanyl dose-dependently reduced respiratory minute volume (ml/min; MVb) that was reversible by naloxone. Caffeine and theophylline each significantly increased basal MVb. Theophylline, but not caffeine, completely reversed oxycodone-depressed respiration. In contrast, neither methylxanthine elevated fentanyl-depressed respiration at the doses tested. Despite their limited efficacy for reversing opioid-depressed respiration when administered alone, the methylxanthines safety, duration, and mechanism of action supports further evaluation in combination with naloxone to augment its reversal of opioid-depressed respiration.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"229 ","pages":"Article 173601"},"PeriodicalIF":3.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9941778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alzheimer's disease (AD) is a long-term neurodegenerative condition that impairs cognitive abilities. In brain acetylcholine deficit and oxidative stress may be considered the key pathogenic causes for AD, even though the basic etiology is still unknown. The effects of some novel pyrrolidine-2-one derivatives on the learning and memory deficits caused by scopolamine in mice were examined in the current study. The learning and memory parameters were assessed using the morris water maze test, rota rod test the and locomotor activity. A number of biochemical factors were also evaluated, including acetylcholinesterase (AChE), lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CA), and nitrite oxide (NO) assay. The current study shows that these derivatives were more effective and comparable to donepezil at treating the behavioral and biochemical changes brought on by scopolamine. The observed results showed pyrrolidine-2-one derivatives as a promising candidate for diseases associated with cognitive deficits.
{"title":"Neuroprotective effects of novel pyrrolidine-2-one derivatives on scopolamine-induced cognitive impairment in mice: Behavioral and biochemical analysis","authors":"Swati Pant, Mohan Gupta, Tulika Anthwal, Monika Chauhan, Sumitra Nain","doi":"10.1016/j.pbb.2023.173602","DOIUrl":"10.1016/j.pbb.2023.173602","url":null,"abstract":"<div><p><span><span><span>Alzheimer's disease<span> (AD) is a long-term neurodegenerative condition that impairs cognitive abilities. In brain acetylcholine deficit and </span></span>oxidative stress<span> may be considered the key pathogenic causes for AD, even though the basic etiology is still unknown. The effects of some novel pyrrolidine-2-one derivatives on the learning and memory deficits caused by scopolamine in mice were examined in the current study. The learning and memory parameters were assessed using the morris </span></span>water maze<span> test, rota rod test the and locomotor activity. A number of biochemical factors were also evaluated, including acetylcholinesterase<span> (AChE), lipid peroxidation (LPO), </span></span></span>reduced glutathione<span><span><span> (GSH), superoxide dismutase (SOD), </span>catalase<span> (CA), and nitrite oxide (NO) assay. The current study shows that these derivatives were more effective and comparable to donepezil at treating the behavioral and biochemical changes brought on by scopolamine. The observed results showed pyrrolidine-2-one derivatives as a promising candidate for diseases associated with </span></span>cognitive deficits.</span></p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"229 ","pages":"Article 173602"},"PeriodicalIF":3.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9941805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}