Psychopharmacology最新文献

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.

Rationale: Depression is a common mood disorder that seriously affects the quality of life and working ability of patients. Zhi-Zi-Hou-Po Decoction (ZZHPD), a classical formula from the Traditional Chinese Medicine (TCM), is widely used to treat depression. Although ZZHPD exhibits potent antidepressant effects, its specific mechanism of action and active ingredients remain unknown.

Objectives: This article focused on identifying and analysing the major phytochemical in ZZHPD that exhibit antidepressant effects. It also provided theoretical data for the standardized clinical application of ZZHPD.

Methods: A systematic review of the materia medica, chemical composition, and pharmacological effects from multi-source literature databases to elucidate the antidepressant mechanism of ZZHPD. And further validation was performed using a comprehensive bioinformatics analysis of network pharmacology and molecular docking.

Results: The antidepressant effect of ZZHPD is achieved through multiple pathways and targets. The key phytochemical constituents of ZZHPD include 3 categories, iridoids, flavonoids, and lignans, which are specifically included geniposide, magnolol, honokiol, hesperidin, hesperetin, naringin, naringenin, nobiletin, and 3,5,6,7,8,3',4'-heptamethphoxyflavone (HMF). The main antidepressant mechanisms include enhancing monoaminergic system function, inhibiting neuroinflammation, restoring HPA axis negative feedback, enabling neurogenesis and neuroplasticity, neuroprotective effects, inhibition of neuronal apoptosis and pyroptosis, antioxidative stress, and regulation of noncoding RNA.

Conclusions: In summary, ZZHPD demonstrates antidepressant effects through multi-component, multi-target, and multi-pathway mechanisms. It shows promise for treating depression at the molecular, cellular, and systemic levels, with significant clinical application value.

Rationale: Animal models of cannabinoid self-administration are critical for advancing our understanding of the neurobiology of cannabis use and for developing medications for Cannabis Use Disorder. Use of vapor inhalation models have translational relevance, as the majority of humans who use cannabis do so by inhalation (e.g., smoking, vaporization).

Methods: Adult male and female Sprague Dawley rats (N = 96, 6-12 per sex/group) were pre-exposed to vaporized THC or vehicle (Veh; 100% propylene glycol). Rats were then trained to self-administer vapor puffs of either THC (50 mg/ml training dose) or Veh under a fixed ratio (FR) 1 schedule. Responding was then assessed under increasing response costs (FR1-5) and different 'doses' (50-200 mg/ml) of THC. As a secondary study aim, we assessed the effects of pre-exposure to THC (or Veh) on self-administration of THC vapor or Veh vapor.

Results: There were no differences in responding for THC and Veh vapor under an FR1 schedule. As the FR increased, rats increased their responses for THC, and female rats in the THC group responded more than female rats in the Veh vapor group. When the THC concentration was increased or decreased from the training dose, rats self-administering THC vapor adjusted their responding. THC vapor pre-exposure significantly increased self-administration of THC vapor.

Conclusions: Adult male and female rats self-administered THC vapor in a sustained manner across several months. Rats increased their responding to obtain THC vapor as the response cost increased and titrated their THC intake based on the THC concentration available. These data demonstrate sex differences in THC vapor reinforcement and that lower THC doses and THC pre-exposure are critical for engendering the reinforcing effects of THC vapor. This is a promising model of THC vapor self-administration.

Rationale & objective: Exposure to traumatic stressors can have detrimental effects on one's well-being. Alcohol is often used as a coping mechanism to alleviate stress, leading to the development of alcohol use disorder (AUD). Furthermore, sex dimorphisms in stress and AUD alter their progression and sustenance. To investigate these interactions for effective treatment strategies, validated and exhaustive preclinical models are necessary. Here, we designed a comprehensive study that examines how traumatic stress influences ethanol drinking patterns and PTSD-like phenotypes in male and female mice with Single Prolonged Stress (SPS).

Methods: Male and female C57BL/6 J mice underwent SPS, a model of traumatic stress consisting of a series of consecutive stressors, followed by a 7-day stress incubation period. Mice then underwent a series of tests for aversive state, fear discrimination, and drinking patterns during continuous and limited ethanol access.

Results & conclusions: SPS selectively increased negative affect and startle responses in male mice, while females were unaffected. SPS disrupted discrimination adjustment between fear and safety cues during extinction, while ethanol exposure attenuated overall fear responses. SPS maintained baseline sex differences in consumption. Furthermore, female consumption increased when access was provided prior to and continuously throughout SPS and fear conditioning, contrasting with groups exposed to ethanol afterwards. In summary, we identified a distinct sex specific relationship between traumatic stress, fear memory, and the timing of ethanol consumption. We highlight SPS as a robust translational model for exploring the sex-specific neurobiological mechanisms driving traumatic stress-induced affective disturbances.