Psychopharmacology最新文献

Rationale: Apocynin-tandospirone derivatives (ATDs) have recently been shown to ameliorate methamphetamine (MAP)-induced behavioral abnormalities when administered chronically, presumably through antioxidant and interneuron-related mechanisms. However, their acute behavioral profile remains unclear.

Objective: In this study, we examined whether acute ATD administration exerts antipsychotic-like effects in rats.

Methods: Rats received acute treatment with ATDs (A-2, A-3, A-4), atypical antipsychotics, or saline, followed by assessments of spontaneous locomotor activity and MAP-induced hyperlocomotion. Prepulse inhibition (PPI), dopamine (DA) concentrations in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAC) were also measured.

Results: Acute ATD administration did not reduce spontaneous activity and failed to suppress MAP-induced hyperlocomotion. Instead, all three ATDs significantly enhanced MAP-induced locomotor responses, with A-3 showing dose-dependent potentiation. ATDs did not improve MAP-induced PPI deficits, except for a modest effect of high-dose A-3. Consistent with these behavioral outcomes, DA levels in the NAC were unchanged, and only small increases in mPFC DA were observed with A-2 and high-dose A-3.

Conclusion: The results demonstrate that acute ATD administration neither suppressed MAP-induced behavioral abnormalities nor produced marked neurochemical changes, but instead enhanced MAP-induced locomotor activity, indicating a clear dissociation from their previously reported chronic effects.

Alzheimer's disease (AD) represents major cognitive and memory decline in the elderly patients. Although Montelukast has traditionally been used for the treatment of asthma, its role in prevention of neuropathological changes and memory decline in AD have recently been reported in literature. However, the brain availability through oral administration of Montelukast is limited due to its poor blood-brain barrier permeation. This study has highlighted that the intranasal administration of Montelukast can provide a considerable brain bioavailability of Montelukast in mice. In addition, intranasal administration of Montelukast showed a significant improvement of spatial and cognitive memory, prevention of Aβ accumulation, astrocyte activation, along with improved redox balance and neuronal density in the hippocampus and cortex regions in the amyloid-beta_1-42 (Aβ_1-42)-induced animal model of AD. These neuroprotective effects were found to be better through intranasal administration of Montelukast in comparison to its oral administration at the equivalent dose. These results suggest that Montelukast may be administered through intranasal route to achieve a significant therapeutic effect in the pathophysiology of AD.

Objective: This systematic review and meta-analysis evaluated the efficacy and safety of trazodone for managing sleep disturbances in patients with depression, addressing its dual role in improving sleep quality and depressive symptoms.

Methods: Following PRISMA guidelines, a comprehensive search was conducted across PubMed, Scopus, Cochrane Library, PsycInfo, and Web of Science from inception to February 2025. Randomized controlled trials (RCTs) assessing trazodone's effects on sleep and depression in depressive patients were included. Data extraction, quality assessment using the Cochrane ROB2 tool, and meta-analysis were performed, utilizing the standardized mean difference (SMD) and odds ratios (ORs).

Results: Ten RCTs (1,029 participants) were included. Trazodone significantly improved sleep quality (Pittsburgh Sleep Quality Index: SMD = -0.827, 95% CI: -1.331 to -0.323, p = 0.001) and reduced depression severity (Hamilton Depression Rating Scale: SMD = -0.365, 95% CI: -0.480 to -0.249, p < 0.001). Clinical Global Impression scores showed non-significant trends favoring trazodone (SMD = -0.209, p = 0.118). Adverse effects were more frequent with trazodone, including blurred vision (OR = 17.50, 95% CI: 2.28-134.02), somnolence (OR = 7.34, 95% CI: 2.91-18.50), and sedation (OR = 6.53, 95% CI: 3.59-11.87).

Conclusion: Trazodone demonstrates robust efficacy for improving sleep and depressive symptoms in patients with comorbid insomnia and depression. However, its benefits must be weighed against a higher risk of adverse effects, particularly somnolence and visual disturbances. Clinicians should prioritize risk stratification and consider trazodone for patients requiring rapid symptom relief while integrating non-pharmacological interventions for long-term management.

Medicinal cannabis use is increasing worldwide, yet its impacts on driving safety in frequent users are not clearly understood. A more comprehensive understanding of the effects of THC on driving behaviour in frequent users is needed to guide drug driving policy and evidence-based advice for medicinal cannabis consumers. This study investigated the acute effects of orally ingested THC oil on medicinal cannabis users': (a) hazard perception skill performance; (b) driving-related risk-taking behaviours (speeding propensity, following distance, gap acceptance); (c) self-perceived hazard perception skill performance; and (d) self-perceptions of driving skills and safety. A within-subjects design was used to compare scores on validated video-based measures of hazard perception skill and risk-taking behaviours, along with self-report measures, between baseline (no THC) and post-consumption. Although participants' (N = 41) actual hazard perception skill performance did not significantly decline from baseline to post-consumption, their perceived performance did (with no significant correlation between the two in either condition). In the other video-based measures, participants selected significantly slower speeds and longer following distances post-consumption (but gap acceptance behaviour was unchanged). There was no significant change in self-perceptions of driving skills and safety after correction for multiple tests. While there was no evidence that oral ingestion of THC oils by medicinal cannabis users impacted hazard perception skill performance, they were unable to accurately self-assess their performance, regardless of whether they had consumed THC. Further, medicinal cannabis patients engage in compensatory strategies, specifically by reducing their speed and increasing their following distance following the consumption of THC.

Rationale: There is a connection between respiratory pathologies and panic disorder, since episodes of hypercapnia can trigger anxiety-related behaviors. The locus coeruleus (LC) is a CO₂/pH chemosensitive region capable of generating emotional and physical responses during stress episodes. The acid-sensitive ion channel type 1a (ASIC1a) participates in the panicogenic response induced by CO₂.

Objectives: Our study investigated the role of ASIC1a channels in the LC in detecting hypercapnic acidosis and their participation in the respiratory and behavioral responses induced by CO₂.

Methods: We tested the effects of injection of an ASIC1a antagonist [Psalmotoxin-1 (Pstx-1-50 ng/0.1uL)] into the LC of C57BL/6 male and female mice on respiratory, metabolic, and behavioral responses to 20% CO₂. To assess the role of ASIC1a channels in basal activity and CO₂ chemosensitivity of LC neurons, whole-cell patch-clamp recordings were performed on brainstem slices from male mice using Pstx-1 (0.050 µg/mL).

Results: Pstx-1 intra-LC did not change ventilation and metabolism under normocapnic and hypercapnic conditions in both male and female mice. As to CO₂-behavioral responses, Pstx-1 injection decreased the number of jumps in males, but there was no significant difference in females. In vitro, Pstx-1 reduced the activity of LC chemoreceptors under hypercapnia in males, but no change was observed under control conditions.

Conclusions: ASIC1a channels in the LC do not participate in respiratory control under normocapnia and hypercapnia, but are involved in CO₂-induced panic behavior, demonstrating a sex-dependent response. Furthermore, ASIC1a channels contribute to the CO₂ chemosensitivity of LC neurons in males.