Psychopharmacology最新文献

Rationale: Adult neurogenesis in the brain enhances memory retention, particularly under conditions of compromised hippocampal function. However, it is unclear whether changing neurogenesis levels would affect the longevity of a physiological memory trace.

Objective: Here, we hypothesized that the mechanisms of potentially pro-neurogenic treatments and the nature of the memory trace are determinant factors in defining whether memories persist.

Methods: We subjected adult male C57Bl/6 mice to behavioral procedures that evoke fear memories, which naturally fade within 10 days. We then examined whether increasing adult neurogenesis could prevent the natural decay of these memories. We investigated the hippocampus's dependence on these memories using context, sound, or smell as the conditioned stimuli. Memantine (MEM), andrographolide (ANDRO), and an enriched environment (EE) were used to investigate their effects on neurogenesis and memory retention.

Results: EE and ANDRO increased neurogenesis in the dentate gyrus of the hippocampus (DG). Interestingly, neither treatment altered the progenitor cell population in the DG of Nestin-GFP mice. To gain further insight into the effects of ANDRO and MEM, we recorded the oscillations in DG local field potentials (LFP) immediately and 7 days after the pharmacological treatments. Acute administration of MEM increased slow gamma power in DG, while ANDRO had the opposite effect. Finally, we tested whether treatments would extend the fear conditioning memory. ANDRO and EE increased fear memory, but only for contextual fear conditioning (CFC).

Conclusions: Our study shows that different methods allegedly used to increase adult neurogenesis have varying effects on DG neurophysiology. Moreover, it suggests that memories reliant on the hippocampus, such as CFC, may be more prone to alterations in adult neurogenesis than memories less dependent on this brain region, such as auditory and olfactory conditioned fear memories.

There is a common mechanism in the pathogenesis of central nervous system diseases: Neuronal damage causes a dissipation of the intermediate metabolites, triggering a wider range of injury and inflammation. Due to the selective permeability of the blood-brain barrier, the drug treatment of neurological diseases is not effective. Nanomedicine, with good biocompatibility and high plasticity, can pass through the blood-brain barrier through various mechanisms and targeted the lesion: The nano-delivery system helps drugs cross the blood-brain barrier while taking advantage of its high drug-loading capacity to achieve combined treatment; Nano-enzymes can simulate the enzymatic reaction in biological body to remove metabolic substances, and are more stable and economical than biological enzymes; Individual nanomedicine can regulate the differentiation process of neural stem cells from the genetic level, increase the number of neurons, and repair injured nerves. Nanomaterials can not only improve the pharmacokinetics and pharmacodynamics, but also play the function of focal location to monitor and evaluate the disease and condition during the treatment of nervous system diseases. In this paper, the mechanism of nanomaterials penetrating the blood-brain barrier (BBB) and locating lesions in various nervous system diseases is reviewed, which opens up new ideas for further exploring the application of nanotechnology in central nervous system diseases.

Rationale: Although cognitive fatigue commonly occurs during sports, effective strategies to improve it during exercise have not been established.

Objectives: This study determined whether high-cocoa flavanol (HCF) consumption improves reaction time and inhibitory executive function impairments during prolonged cognitive load combined with aerobic exercise.

Methods: In this randomized crossover study, 18 healthy males (22 ± 2 years) participated in both low-cocoa flavanol (LCF) and HCF trials. Double-blinded capsules (LCF 50 mg and HCF 500 mg) were consumed 1 h before a 50-min cognitive exercise dual-tasking protocol, which included a color-word Stroop task (CWST) and moderate-intensity cycling. The CWST assessed reaction time and reverse-Stroop interference score as indicators of inhibitory executive process.

Results: Reaction time (LCF 774 ± 146 ms vs. HCF 731 ± 101 ms, P < 0.01) and reverse-Stroop interference score (LCF 6.2 [3.2-15.5] vs. HCF 4.6 [1.2-11.4], P < 0.01) were significantly better 1 h after HCF consumption than after LCF consumption, indicating that HCF improved both reaction time and the inhibitory executive process at rest. During the 50-min cognitive-exercise dual-tasking protocol, HCF consumption resulted in faster reaction time (LCF 712 ± 122 ms vs. HCF 685 ± 111 ms, P < 0.05) and better inhibitory executive process (LCF 8.4 ± 5.0 vs. HCF 6.6 ± 3.5, P < 0.05) compared to those following LCF consumption.

Conclusions: These findings suggest that flavanol-rich cocoa may improve reaction time and inhibitory executive process impaired by cognitive fatigue during aerobic exercise.

Rationale: Animal models of addiction often study changes in motivation after repeated self-administration of a single drug. However, human users frequently consume multiple drugs, potentially altering their motivation and affective response.

Objectives: This study investigated how individual rats differentially self-administer cocaine and heroin, and whether motivation to take each drug was associated with affective states, as indicated by ultrasonic vocalisations (USVs). We also determined whether opioid antagonism (via naltrexone), which is known to decrease heroin-taking and associated USVs, also altered motivation and vocalisations for cocaine.

Methods: Male Lister Hooded rats, with surgically implanted catheters, self-administered cocaine and heroin on alternating days. Motivation was evaluated via drug intake escalation (fixed-ratio schedule), behavioural adaptation to dose reductions (behavioural economics), and progressive ratio breakpoints (with or without naltrexone). USVs were recorded and analysed using machine learning software (DeepSqueak).

Results: Rats escalated intake of both drugs during training. At the start of each session, rats rapidly self-administered cocaine or heroin; this drug-loading behaviour was associated with an increase in 50 kHz vocalisations. Rats altered their cocaine and heroin intake when drug doses decreased, and this was accompanied by reduced 50 kHz USVs. Lastly, naltrexone reduced progressive ratio breakpoints for heroin but not cocaine; naltrexone also decreased 50 kHz USVs for heroin (an effect which persisted).

Conclusions: Distinct patterns emerged in motivation and USVs between cocaine and heroin self-administration. Notably, USV frequency did not consistently align with motivation, especially when drug dosage changed. Future research may clarify this divergence.

Rationale: Alcohol-induced blackouts (AIBs) are common in college students and are associated with other alcohol-related consequences. Alcohol-nicotine co-use is also common in this population. Nicotine has cognitive-enhancing properties impacting multiple cognitive domains, including those impaired by alcohol (e.g., attention), but it is unclear whether nicotine affects AIB risk or the relationship between AIBs and other alcohol-related consequences.

Objectives: We examined the moderating effects of nicotine use on the associations between (a) alcohol and AIBs and (b) AIBs and other consequences (total and serious: sexual, legal, or those with potential to cause great harm).

Methods: College students who reported past semester heavy drinking and at least 1 AIB (N = 79, 55.7% female, 86.1% White) wore alcohol sensors and completed daily diaries over four consecutive weekends (89.9% completion). Multilevel models were conducted to test for moderating effects of nicotine (yes/no) on the alcohol-AIB relationship and the AIB-consequence relationship, adjusting for sex, race/ethnicity, and baseline nicotine use.

Results: Concurrent alcohol and nicotine use did not moderate the alcohol-AIB relationship, but weakened the associations between AIBs and both (1) total consequences and (2) serious consequences. On days with nicotine use, AIBs were associated with approximately 30% fewer total consequences and 50% fewer serious consequences than days without nicotine use.

Conclusions: College students experienced fewer total and serious consequences on AIB nights when nicotine was used compared to AIB nights when nicotine was not used. Future research should explore potential mechanisms underlying the observed effects.

Rationale: Conventional pharmacotherapy for depression faces numerous challenges, including side effects. Moreover, less than 50-70% of patients fully respond to treatment, and 20-30% experience recurrence. This has led to a growing interest in alternative treatments, particularly phytotherapy. Among various plant-based compounds, asiatic acid has gained attention due to its multidirectional therapeutic properties.

Objective: The aim of this study was to evaluate whether asiatic acid could enhance the antidepressant effects of conventional drugs (imipramine, reboxetine, and escitalopram).

Methods: The antidepressant-like effect was tested by the forced swim test and in the tail suspension test in male Albino Swiss mice. Additionally, pharmacokinetic studies and biochemical analyses were carried out.

Results: According to obtained results, asiatic acid at a sub-active dose (5 mg/kg) significantly potentiates the antidepressant activity of imipramine (15 mg/kg), reboxetine (2.5 mg/kg), and escitalopram (2 mg/kg). It was demonstrated that asiatic acid (5 mg/kg) did not increase serum or brain levels of the tested antidepressants. However, when given concurrently with escitalopram (2 mg/kg) it elevated concentrations of catalase and glutathione peroxidase as well as decreased levels of TBARS in mice brains. Co-administration of asiatic acid with imipramine (15 mg/kg) and reboxetine (2.5 mg/kg) reduced concentrations of TBARS in the tested tissue.

Conclusions: Our findings give a new light on the potential use of asiatic acid in the management of depression. The terpenoid has antidepressant properties, potentially making it a valuable addition/adjunct to conventional treatment.

Rationale: The expression of addictive behaviors is linked to the structural plasticity of dendritic spines in the nucleus accumbens (NAcc). While radixin is known to contribute to morphological changes in dendritic spines, its role in the NAcc, specifically in the structural plasticity of dendritic spines and related drug-induced behavioral changes, is not well understood.

Objective: In the present study, we investigated the effects of radixin manipulation in the NAcc core on amphetamine (AMPH)-induced locomotor activity, both in association with and independent of a specific environment. Additionally, we examined the accompanying changes in dendritic spine density in this region.

Methods: We used a phosphomimetic pseudo-active mutant form (Rdx-T564D) and wild-type (Rdx-WT) radixin in conditioning and context-independent sensitization models induced by AMPH (1 mg/kg).

Results: We observed that Rdx-T564D in the NAcc core selectively inhibited the expression of non-associative locomotor sensitization induced by AMPH. Conversely, overexpression of Rdx-WT in this region inhibited both conditioned locomotor activity and context-specific locomotor sensitization. Spine analysis revealed that the increase in mature thin spine density observed in the context-paired group was specifically suppressed by Rdx-WT, but not by GFP or Rdx-T564D.

Conclusions: This study revealed that associative and non-associative forms of AMPH-induced reward memory are differentially regulated by radixin manipulation in the NAcc core, suggesting a critical role of radixin in psychomotor stimulant addiction.

Objective: Investigating the effects of sertraline on depressive symptoms and serum inflammatory factors in adolescents with depression to verify the relationship between depressive state and serum inflammatory factors.

Methods: Retrospective collection was conducted on 50 adolescent depression patients treated with sertraline admitted to a hospital from January 2021 to December 2022 as the observation group. By propensity score matching, 50 non pharmacological adolescent depression patients were matched as a control group in a 1:1 ratio. Kutcher Adolescent Depression Scale (KADS-11) scores were retrospectively analyzed before treatment (T1) and on 8th week after treatment (T5). At the same time, the scores of interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-11 (IL-11) scores, and interleukin-2 (IL-6), as well as tumor necrosis factor - α (TNF-α) before treatment (T1), on 1st week (T2), 2nd week (T3), 4th week (T4), and 8th week (T5) of the two groups were also retrospectively studied. Pearson correlation analysis was used to verify the relationship between depressive symptoms and serum inflammatory factors in adolescents with depression. Multiple linear regression analysis was used to find out the effect of serum inflammatory factors on depressive symptoms in adolescents with depression.

Results: Attention problems, body discomfort, and total score of KADS-11 in control group were significantly decreased compared with those before treatment at T5 (P < 0.05). Every score and total scores of KADS-11 in observation group were significantly lower than those before treatment (P < 0.05), and the data in observation group were lower than those in control group (P < 0.05). According to repeated measurement ANOVA, there were statistically significant differences in IL-1β, IL-2, IL-6, and TNF-α levels between the two groups (P < 0.05), and the change of serum inflammatory factors in the observation group was more obvious than that in the control group. Pearson correlation analysis showed that the total scores of KADS-11 were positively correlated with serum inflammatory factors (r = 0.881 ~ 0.932, P < 0.05). Linear regression analysis showed that IL-1β, IL-2, IL-6, and TNF-α had positive effects on the total score of KADS-11 (B = 0.145-0.444, P < 0.05).

Conclusion: Sertraline can effectively relieve the symptoms of depression in adolescents and reduce inflammation. Serum inflammatory factors have a significant relationship with depressive symptoms, so it can be considered as an evaluation index of treatment effect.

Objectives: This study aims to investigate the neuroprotective effects of Ginsenoside Rg1 in alleviating P-chlorophenylalanine (PCPA)-induced insomnia and explore its underlying mechanisms involving the inhibition of NOD-Like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation and pyroptosis through the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway in mice.

Methods: Sprague-Dawley rats were randomly divided into five groups: control, sleep deprivation (SD, PCPA-induced insomnia), and three treatment groups receiving different doses of Ginsenoside Rg1 (low, medium, and high). Behavioral assessments included the Pentobarbital Sodium-Induced Sleep Test (PIST), Sucrose Preference Test (SPT), and Morris Water Maze (MWM). Histopathological and immunofluorescence evaluations of hippocampal tissues were performed. Enzyme-Linked Immunosorbent Assay (ELISA) was used to measure neurotransmitter levels (5-Hydroxytryptamine [5-HT], 5-Hydroxytryptophan [5-HTP], Gamma-aminobutyric acid [GABA], glutamate [GLU]) and pro-inflammatory cytokines (Tumor Necrosis Factor Alpha [TNF-α], Interleukin-6 [IL-6], Interleukin-1 beta [IL-1β], Interleukin-8 [IL-8]). In vitro, corticosterone-induced neurotoxicity in HT22 hippocampal cells was assessed, and the role of the Nrf2/HO-1 pathway was examined through molecular docking, gene silencing, and Western blot.

Results: Ginsenoside Rg1 treatment significantly improved PCPA-induced insomnia symptoms in a dose-dependent manner, as evidenced by reduced sleep latency, increased sleep duration, restored sucrose preference, and improved spatial memory. Histopathological analysis revealed that Ginsenoside Rg1 mitigated neuronal damage and astrocytic activation. Neurotransmitter imbalances were corrected, and inflammation was alleviated, as reflected by reductions in pro-inflammatory cytokines and increased interleukin-10 (IL-10) levels. Mechanistically, Ginsenoside Rg1 inhibited NLRP3 inflammasome activation, pyroptosis, and reduced IL-1β and IL-8 levels in both in vivo and in vitro models. The activation of the Nrf2/HO-1 pathway was further confirmed by molecular docking, immunofluorescence, and Western blot, demonstrating that Nrf2 activation was critical for the anti-inflammatory effects of Ginsenoside Rg1.

Conclusion: Ginsenoside Rg1 effectively alleviates PCPA-induced insomnia by inhibiting NLRP3 inflammasome activation and pyroptosis, with its neuroprotective effects mediated through the activation of the Nrf2/HO-1 pathway. These findings suggest Ginsenoside Rg1 as a potential therapeutic agent for insomnia and related neuroinflammatory conditions.