Journal of Psychopharmacology最新文献

Background: Nicotine is largely responsible for the initiation and maintenance of tobacco dependence and contributes to a global health problem.

Aims: This study characterizes nicotine oral consumption and preference in male and female mice of several Diversity Outbred (DO) founder strains: C57BL/6J, A/J, 129S1/SvImJ, PWK/PhJ, NOD/ShiLtJ, and CAST/EiJ. It assesses the impact of nicotine concentration on intake and preference, the potential interaction of strain with sex, and estimates the degree of heritable variation in nicotine consumption.

Methods: Two-bottle choice oral self-administration paradigm was used to assess nicotine intake, nicotine preference, and total fluid intake in male and female mice of each strain in a concentration-response manner. A conditioned place preference (CPP) test was performed to evaluate the rewarding and aversive effects of nicotine in certain strains after systemic administration of the drug.

Results: The highest nicotine-consuming strain was found to be 129S1/SvlmJ, and the lowest nicotine-consuming strain was A/J. Strain differences in nicotine intake were not due to differences in bitter and sweet tastes as shown in the saccharine and quinine two-bottle choice tests. A/J strain showed no significant CPP for nicotine while the 129S1/SvImJ strain showed a significant CPP for nicotine and a higher preference when compared to the C57BL/6J strain. Heritability estimates of nicotine intake were sex dependent and concentration dependent.

Conclusions: Data support that nicotine consumption patterns are heritable with an influence of genotype in a voluntary oral self-administration paradigm. Results pave the way for future studies with the highly recombinant DO mice that might lead to the identification of novel genetic loci and genes influencing nicotine consumption.

Background: Social behaviour is the expression of one of the most generally accepted independent dimensions of personality. Serotonergic neurotransmission has been implicated in typical social response and drugs that promote serotonin (5-hydroxytryptamine (5-HT)) release have prosocial effects. By using the social interaction test, we have previously demonstrated sociability as a temperamental trait in male Wistar rats.

Aims: To assess sociability in male rats of the Sprague-Dawley strain and in female rats of both Wistar and Sprague-Dawley strain, and extracellular levels of 5-HT in rats with high and low sociability (high sociability (HS)- and low sociability (LS)-rats).

Methods: Social interaction test conducted with different weight-matched partners was used to assess sociability, and in vivo, microdialysis was performed before and after administration of a low dose (2 mg/kg) of parachloroamphetamine (PCA) in the prefrontal cortex, dorsamedial striatum and ventral tegmental area.

Results: Similarly to male Wistar rats, female Wistars and Sprague-Dawley rats of both sexes displayed trait-wise sociability. Male Wistar HS-rats had lower extracellular levels of 5-HT in prefrontal cortex at baseline and after administration of PCA, and higher PCA-induced increase of extracellular 5-HT in ventral tegmental area. In dorsomedial striatum, PCA elicited a comparable increase in extracellular dopamine in HS- and LS-rats, but higher release of 5-HT in HS-rats. Comparison of PCA-induced 5-HT release in prefrontal cortex of male and female Sprague-Dawley rats revealed a larger 5-HT response in female HS-rats.

Conclusions: 5-HT release potential is higher in rats with high expression of sociability trait, whereas some regionally variable differences may be related to relative contributions of social motivation and anxiety in shaping social behaviour.

Background: Limited research considers the quantity and potency of cannabis products along with social context on the subjective effects of real-world cannabis use.

Aims: This study examined the subjective effects of acute use as a function of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) doses and social context during cannabis use episodes.

Method: Ninety-six participants (43.75% male, M_age = 35.73) reporting weekly cannabis use completed a baseline self-report battery assessing cannabis use. Then, THC and CBD potency and quantity of the cannabis product, social context, and subjective experience were assessed through self-initiated surveys after cannabis use episodes during a 14-day ecological momentary assessment (EMA).

Results: Greater feeling high and liking were significantly associated with a higher THC dose than one's average (b = 0.03, p < 0.001; b = 0.02, p < 0.001) and social use (b = 0.38, p < 0.001; b = 0.20, p = 0.01). A higher CBD dose than one's average (b = 0.01, p = 0.04) was significantly associated with greater liking. A significant interaction effect of THC dose and social context (b = 0.01, p = 0.02) was observed such that solitary use had a negative association between THC dose and disliking (b = -0.01, p = 0.04), and social use had a null association (b = 0.003, p = 0.25). Individuals with greater cannabis problems reported lower liking (b = -0.18, p = 0.03) and higher disliking (b = 0.08, p = 0.02), but not feeling high, on average, across the EMA protocol.

Conclusion: Social context plays an important role in the subjective experience of cannabis use. Interventions targeting cannabis problems could highlight the evidence that individuals with greater cannabis problems might experience less liking but more disliking in general across use episodes to effectively challenge expectancies/motives of use.

Background and aims: Early-life adversities are known to alter drug reward processing in rodents. Despite the well-known link between early adversity and the risk of substance use disorder, few studies have measured how childhood adversity affects human drug reward. Here, we assessed the relationship between historical childhood adversities and responses to single doses of methamphetamine, d-amphetamine or buprenorphine in healthy participants.

Methods: Using a secondary analysis approach, we assessed the impact of childhood adversity on drug effects from three randomised, placebo-controlled studies in which healthy volunteers received methamphetamine (20 mg oral; n = 35), d-amphetamine (20 mg oral; n = 54) or buprenorphine (0.2 mg sublingual; n = 35). Ratings of feeling effect, liking, disliking, feeling high and wanting more of the drug were collected 15-210 min post-administration, and heart rate changes were analysed using random-intercept mixed-effect models. The area under the curve from these and previous studies was calculated to visualise the relationship between childhood adversity severity and drug effects.

Results: Greater childhood adversity was associated with reduced feel effects (significant three-way interactions b = -0.07, 95% CI [-0.12, -0.02], p = 0.009), like effects (b = -0.07, 95% CI [-0.13, -0.00], p = 0.038) and feel high (b = -0.06, 95% CI [-0.10, -0.01], p = 0.020) towards the stimulant drugs 90-180 min post-administration.

Conclusions: Childhood adversity was not significantly associated with other subjective or heart rate responses to the drugs. Overall, participants with more childhood adversities reported dampened subjective responses to stimulant drugs, but not to buprenorphine. Future studies should examine the generalisability of these relationships, to identify the mechanisms underlying the link between childhood adversity and drug responsiveness.

Background: People who regularly use cannabis exhibit altered brain dynamics during cognitive control tasks, though the impact of regular cannabis use on the neural dynamics serving motor control remains less understood.

Aims: We sought to investigate how regular cannabis use modulates the neural dynamics serving motor control.

Methods: Thirty-four people who regularly use cannabis (cannabis+) and 33 nonusers (cannabis-) underwent structured interviews about their substance use history and performed the Eriksen flanker task to map the neural dynamics serving motor control during high-density magnetoencephalography (MEG). The resulting neural data were transformed into the time-frequency domain to examine oscillatory activity and were imaged using a beamforming approach.

Results: MEG sensor-level analyses revealed robust beta (16-24 Hz) and gamma oscillations (66-74 Hz) during motor planning and execution, which were imaged using a beamformer. Both responses peaked in the left primary motor cortex and voxel time series were extracted to evaluate the spontaneous and oscillatory dynamics. Our key findings indicated that the cannabis+ group exhibited weaker spontaneous gamma activity in the left primary motor cortex relative to the cannabis- group, which scaled with cannabis use and behavioral metrics. Interestingly, regular cannabis use was not associated with differences in oscillatory beta and gamma activity, and there were no group differences in spontaneous beta activity.

Conclusions: Our findings suggest that regular cannabis use is associated with suppressed spontaneous gamma activity in the left primary motor cortex, which scales with the degree of cannabis use disorder symptomatology and is coupled to behavioral task performance.

Background: Methylphenidate is a routinely prescribed treatment for attention-deficit/hyperactivity disorder with misuse potential owing to its perceived performance-enhancing and euphoric properties. Although clinically effective, there is limited understanding of how methylphenidate affects safety-sensitive tasks such as driving when used by healthy individuals.

Aim: Explore the acute effects of 10 mg methylphenidate on driving performance and gaze behaviour.

Methods: Twenty-five fully licensed, healthy adults (mean age = 33.5 ± 7.8 years, 64% male) took part in two 40-min simulated highway drives with simultaneous eye movements monitored using a proprietary automotive-grade driver monitoring system (Seeing Machines). Driving performance was assessed using the standard deviation of lateral position, standard deviation of speed and steering variability. Visual scanning efficiency was determined using ocular metrics, such as fixation duration and rate, gaze transition entropy, and stationary gaze entropy, were assessed to determine visual scanning efficiency.

Results: Methylphenidate significantly improved driving performance by reducing lane weaving and speed variation, particularly in the latter half of the drive. Although a significant reduction in fixation duration was observed, all other ocular metrics remained unchanged.

Conclusions: Methylphenidate mitigates performance decrements typically associated with prolonged and monotonous driving. The absence of pronounced oculomotor effects suggests that a single 10 mg dose of methylphenidate has no deleterious impact on visual scanning behaviour during driving tasks with low-to-moderate cognitive demand. Future research should investigate the effects of methylphenidate under various dosing and driving conditions to better understand its impact.

Trial registration: ACTRN12620000499987.

Background: Cannabidiol (CBD) impacts brain regions implicated in anxiety reactivity and stress reactivity (e.g., amygdala, anterior cingulate cortex (ACC), anterior insula (AI)); however, placebo-controlled studies are mixed regarding CBD's anxiolytic effects. We previously reported that CBD expectancy alone can alter subjective, physiological, and endocrine markers of stress/anxiety; however, it is unclear whether these findings reflect altered brain reactivity. This study evaluated whether CBD expectancy independently alters amygdala resting-state functional connectivity (rsFC) with the ACC and AI following acute stress.

Method: Thirty-eight (20 females) healthy adults were randomly assigned to receive accurate or inaccurate information regarding the CBD content of a CBD-free oil administered during a single experimental session. Following a baseline resting state MRI scan, participants administered their assigned oil sublingually, engaged in a stress task (serial subtraction with negative feedback) inside the scanner, and underwent another resting state MRI scan. Amygdala rsFC with the ACC and AI was measured during each scan, and the subjective state was assessed at six time points. Outcomes were analyzed using ANCOVA.

Results: CBD expectancy (vs CBD-free expectancy) was associated with significantly weaker rsFC between the left amygdala and right ACC (p = 0.042), but did not systematically alter amygdala-AI rsFC (p-values > 0.05). We also replicated our previously reported CBD expectancy effects on subjective stress/anxiety in the scanner context.

Conclusion: CBD placebo effects may be sufficient to alter neural responses relevant to its purported anxiolytic and stress-relieving properties. Future work is needed to replicate these results and determine whether CBD expectancy and pharmacology interact to alter neural anxiety reactivity and stress reactivity.

Background: Mechanisms underlying psychostimulant euphoria remain poorly understood. In adult rats, positive emotional states are associated with alterations in 50-kHz ultrasonic vocalizations (USVs): specifically, "trill" calls are promoted over "flat" calls. Here, we investigated the effects of acute and repeated cocaine administration, and-based on previous findings with amphetamine-their possible dependence on beta-adrenergic receptors.

Methods: Adult male Long-Evans rats received intraperitoneal drug or saline injections before daily USV recording. Fourteen 50-kHz call subtypes were analyzed. In Experiments 1 and 2, cocaine (1-10 mg/kg) and propranolol (10 mg/kg) were tested alone. In Experiment 3, propranolol/cocaine interactions were sought within a conditioned place preference (CPP) procedure. Experiment 4 investigated acute and chronic cocaine effects (Phase 1), and propranolol/cocaine interactions either in an open field (Phase 2) or within a CPP procedure (Phase 3).

Results: In drug-naïve animals, cocaine increased the 50-kHz call rate, with sensitization developing rapidly. After more extended exposure, cocaine now also increased the relative prevalence of trill versus flat calls; effects on other subtypes were also revealed. The beta-blocker propranolol prevented neither cocaine CPP nor cocaine effects on USV emission or locomotion but exerted significant USV-related effects when given alone. CPP magnitude and USV-related measures were uncorrelated.

Conclusions: With long-term intraperitoneal administration, cocaine can alter the relative prevalence of several 50-kHz call subtypes; its ability to promote trill versus flat calls, in particular, is consistent with a positive affect interpretation. Cocaine's behavioral effects (i.e., USV-related, locomotor, CPP) appear independent of beta-adrenergic receptor activity.

Background: Due to the unsatisfactory therapeutic effects of current antidepressants, research has been launched into alternative treatment approaches, such as the administration of psychedelics. Psilocybin, a classic hallucinogen, has been shown to exert considerable positive influence on depression symptoms through its serotonergic and glutamatergic effects. This systematic review and meta-analysis aimed to evaluate the effectiveness of psilocybin in treating depression.

Methods: A comprehensive search of Medline (via PubMed) and the Cochrane Library databases was conducted to identify relevant studies. Inclusion criteria were applied to select studies that investigated the therapeutic impact of psilocybin on depression. A mixed-effects multi-level model was used to estimate the overall effect size. Effectiveness over time was also investigated as a secondary analysis.

Results: The results of the primary analysis revealed a large and clinically observable reduction (SMC: -1.24, 95%CI: -1.83 to -0.65, I²_level2 = 11.39%, I²_level3 = 77.67%) of depressive symptomatology in patients receiving psilocybin in addition to supportive therapy compared to baseline measurements. The decrease was also marked when compared to placebo (p-value = 0.032). The results remained significant even when a secondary analysis assessed the effect in various time intervals since the administration of psilocybin.

Conclusion: This systematic review and meta-analysis substantiate the claim that psilocybin is superior in treating depression compared to established psychotherapy alone used for treating depression. This finding warrants further studies with larger sample sizes and across a longer timeframe.