Psychopharmacology最新文献

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.

Rationale: Cognitive control is crucial for optimal daily functioning and for emotional well-being. Cognitive control has been shown to be modified by experimental manipulations under widely differing experimental conditions, including cognitive training, and pharmacological intervention mainly probing catecholaminergic systems with little focus on the serotonergic system.

Objectives: To explore the role of serotonin on cognitive control in emotional and non-emotional settings.

Methods: Behavioral, electrodermal and prefrontal activity measures were evaluated to compare the effects of single-session task repetition and single-dose serotonergic intervention with escitalopram on cognitive control in healthy participants, using cognitive and emotional Stroop tasks.

Results: For cognitive Stroop, task repetition improved performance both 'on-line' within an ongoing task and 'off-line' after a four-hour delay, and escitalopram had no additional effects on this. In emotional Stroop, escitalopram enhanced the practice-related performance gain, starting from the second stimulus of each block. Compared to placebo, escitalopram also significantly reduced overall rate of premature responses. Regarding brain activation, escitalopram significantly reduced prefrontal activity during cognitive and even more so during emotional Stroop task. Lastly, electrodermal response showed significant habituation during cognitive but not emotional Stroop, in an effect that was not significantly modified by escitalopram.

Conclusions: Cognitive control in emotional and non-emotional settings may respond differently to behavioral and pharmacological manipulations. Escitalopram may selectively improve cognitive control in an emotional setting compared to cognitive control in non-emotional settings.

Introduction: Obesity is a global concern leading to significant morbidity and mortality. Naltrexone-Bupropion (NB) is sought to be a favorable medication in obese patients with or without concurrent psychiatric illness. In this systematic review, we have compared NB's role as an obesity management strategy, against placebo and usual care, for overweight and obese psychiatric and non-psychiatric patients.

Methods: Cochrane Collaboration and PRISMA guidelines were followed for this study. We searched PubMed/Medline, Cochrane, and Clinicaltrials.gov from inception till June 1, 2024. The primary efficacy outcomes were changes in weight, BMI, and waist circumference.

Results: 12 RCTs with 5,367 patients were included in the final review. Eight studies used a combination of 32 mg naltrexone and 360 mg bupropion. Weight-related outcomes were reported in 10 studies. Among 5 studies including psychiatric patients, NB showed substantial weight loss. For non-psychiatric patients, NB resulted in significant weight loss and BMI reduction as well. Psychiatric outcomes assessed with BDI-II scores showed greater depression reduction in NB groups. Biomarker outcomes indicated a decrease in LDL and triglycerides, with an increase in HDL for NB groups.

Conclusion: Our review highlights NB as a potential option in the management of overweight and obese patients with or without psychiatric comorbidity.

Rationale: Patients with non-alcoholic fatty liver disease (NAFLD) may experience non-cognitive impairments such as anxiety and depression. However, the specific mechanism of the association between liver injury and neurological disorders is unclear.

Objectives: In this study, we aimed to explore the relationship and underlying mechanism between high-fat fructose diet (HFFD)-induced liver injury and anxiety-like behavior in mice.

Methods: A mouse model of NAFLD was established using an HFFD, and behavioral tests were performed to detect anxiety-like behaviors in mice; moreover, we used enzyme linked immunosorbent assay (ELISA) to detect glutamate levels in treated and normal diet (ND) mice, as well as to explore inflammation levels in mice using immunofluorescence and other methods.

Results: Mice in the HFFD-treated group exhibited anxiety-like behaviors, as well as elevated serum lipid and glutamate levels, increased liver injury, and hepatic tissue fat accumulation. Additionally, HFFD-fed mice exhibited elevated levels of IL-6, IL-1β, and TNF-α in the liver, hippocampus, and cortex compared with the ND counterparts; HFFD-induced astrocyte and microglial activation was detected in the cortical and hippocampal regions. However, corilagin treatment alleviated these HFFD-associated pathological changes. Corilagin did not ameliorate anxiety behaviors in mice in the absence of liver injury.

Conclusion: Our results indicated that the HFFD-induced NAFLD and mild hepatic fibrosis led to elevated levels of glutamate and aminotransferases, which infiltrated the brain, causing inflammation, and subsequently induced anxiety-like behaviors in mice. These pathological and behavioral manifestations were ameliorated through corilagin intervention. This study provides a possible underlying mechanism between HFFD and neurological disorders.

Rationale: Postnatal neurogenesis is the process of new nerve cell formation that occurs after birth. The disruption of the neurogenesis process is a significant hypothesis in the development of mental disorders and diseases such as depression, anxiety disorders or schizophrenia, as well as neurodegenerative diseases such as Alzheimer's disease.

Objective: The objective of this study was to investigate, based on the existing literature, whether naturally occurring alkaloids have an impact on postnatal neurogenesis and, if so, whether this effect is beneficial or detrimental.

Methods: An advanced search was conducted using the databases PubMed and Google Scholar, employing the terms "alkaloid" AND "neurogenesis." The research focused on in vitro studies using cell lines, including C17.2, HT-22, BV-2, and SH-SY5Y, in addition to in vivo studies involving zebrafish (Danio rerio), Wistar rats and mice.

Results: The research indicated that some of the alkaloids have a beneficial impact on postnatal neurogenesis through their pleiotropic mechanisms of action. This is evidenced by their anti-inflammatory and anti-oxidant effects, ability to increase brain-derived neurotrophic factor (BDNF) levels, promotion of synapse formation, and direct effect on neural progenitor cells proliferation. However, some alkaloids have been shown to have a negative effect on postnatal neurogenesis through mechanisms that are the opposite of those mentioned above.

Conclusion: There is currently a lack of consensus on whether neurogenesis occurs in Homo sapiens. However, it is known that alkaloids affect the model organisms in different ways, which suggests a potential for these substances to be used therapeutically. Further research is therefore required to investigate this possibility.

Rationale: Rodent models dominate autism spectrum disorder (ASD) research, yet their translational validity is limited for a heterogeneous condition with complex social-vocal phenotypes.

Objectives: To evaluate the zebra finch (Taeniopygia guttata) - a highly social, vocal-learning songbird - as an ASD model by adapting embryonic valproic acid (VPA) exposure and identifying dose-timing conditions that preserve viability while perturbing social behavior.

Methods: We used a 3 × 3 design crossing VPA dose (0, 0.3, 0.6 µmol/egg) with manipulation day (incubation days 8-10). Hatching success, post-hatching survival, growth, and social behavior in a bird-adapted three-chamber test were quantified with mixed-effects models (binomial/Cox/linear/negative binomial, beta-binomial).

Results: Hatching success decreased at 0.6 µmol and with day-8 injections; day-9 performed best. Post-hatching survival was lower at 0.3 µmol versus controls (limited inference for 0.6 µmol due to small n). Growth showed dose×sex interactions: females at 0.6 µmol were lighter with shorter tarsi; wings showed a similar tendency. In sociability (phase 1), time-based measures were unchanged, 0.6-µmol birds made more approaches to the closest perch, while day-8 birds approached less than day-9. In phase 2, time on the familiar-side closest perch showed a day×sex interaction (day-8 females spent less time than day-8 males), and approaches to that perch increased at 0.6 µmol. Overall sociability (combined closest perches) and total activity did not differ by group.

Conclusions: Embryonic VPA in zebra finches yields selective, partly sex-dependent developmental and social effects. Zebra finches remain promising; day-9 intermediate doses (~ 0.35-0.50 µmol) warrant follow-up to map dose-response and balance viability with behavioral detectability.

Rationale: Relevant to the study of neurodevelopmental disorders, maternal immune activation (MIA) models reproduce the high incidence of anxiety disorders and molecular alterations in the cerebellum reported in patients with schizophrenia and autism. In parallel, ketamine, a fast-acting antidepressant, has shown beneficial effects in psychiatric disorders with immune-related components.

Objectives: To investigate anxiety-like behavior, inflammatory status, and oxidative balance in the cerebellum of offspring exposed to MIA and to test the potential effects of ketamine postnatal treatment in reversing the behavior and molecular changes.

Methods: To induce MIA, pregnant Swiss mice were intraperitoneally (i.p.) injected with lipopolysaccharide (LPS; 100 µg/kg/day) or saline (10 mL/kg/day) on gestation days 15 and 16, and subsequently, male offspring were administered saline (10 mL/kg/day) or ketamine (20 mg/kg/day) from postnatal day 36 to 50. On postnatal day 62, the offspring were assessed for anxiety-like behavior, and the cerebellum was collected for analysis of IL-1β, IL-6, TGF-β, and TNF-α gene expression and oxidative balance.

Results: Our results demonstrated that MIA increased anxiety-like behavior in offspring, accompanied by an increase in TNF-α expression, and oxidative imbalance in the cerebellum. Ketamine administration reversed the anxiety-like behavior, as well as attenuated both TNF-α expression and oxidative imbalance.

Conclusions: Our findings suggest that the cerebellum is an important site of long-lasting changes induced by MIA and a relevant target of ketamine's effects. These results highlight the cerebellum's role in pathophysiological processes and its potential as a site for therapeutic intervention in psychiatric disorders.