Neuropsychopharmacology

Abstract The PACt-MD study demonstrated that combined cognitive remediation (CR) and transcranial direct current stimulation (tDCS) slows global cognitive decline in individuals with mild cognitive impairment (MCI) or remitted major depressive disorder (rMDD) over a median follow-up of four years. Prefrontal theta-gamma coupling (TGC), measured via electroencephalography (EEG), is a marker of pre…

Abstract We previously demonstrated that male progeny of cocaine-experienced sires resisted cocaine, expressed as delayed acquisition of cocaine self-administration. Here, we sought to determine whether this phenotype extended to another psychostimulant, methamphetamine (meth). Sires self-administered meth or cocaine or received yoked-saline infusions for 60 days, after which they were mated to n…

Rates of binge drinking have converged significantly between the sexes over recent decades, driven by increased rates of alcohol misuse in women. However, understanding of the fundamental circuitry and neurobiology driving alcohol use in females, or how this may differ from male subjects remains underexplored. Here, we quantified c-Fos expression across 40 brain regions in alcohol naïve, alcohol …

Abstract Cognitive deficits in executive functions such as working memory and cognitive flexibility are central to many brain disorders, yet effective treatments remain limited. Dysfunction of GluN2A-containing NMDA receptors (NMDAR) contributes to these impairments, and positive allosteric modulators (PAM) that selectively enhance GluN2A function offer a promising strategy to rescue cognitive de…

Abstract Refined, non-invasive analgesic delivery methods are essential for improving animal welfare and ethical standards in laboratory rodent research. Here, we evaluated whether the micropipette-guided drug administration (MDA) method, which promotes voluntary consumption using a sweetened condensed milk vehicle, achieves therapeutically relevant plasma and brain concentrations of two widely u…

Abstract The phase 2 ERUDITE (NCT05182476) study evaluated the efficacy and safety of luvadaxistat, a selective ᴅ-amino acid oxidase inhibitor, for cognitive impairment associated with schizophrenia. ERUDITE was a randomized, double-blind, placebo-controlled, parallel-group study in adults with schizophrenia receiving background antipsychotic therapy. Following a 2-week placebo run-in, participan…

Adolescence represents a critical neurodevelopmental period of high vulnerability to the onset of psychiatric conditions. Altered processing of uncertain reward outcomes likely contributes to this vulnerability, yet remains poorly understood. Addressing this knowledge gap, we sought to use the fMRI Reward Flanker Task, originally developed by our group, to examine neural responses to uncertain re…

Abstract Adolescents experience extensive neurocognitive development, with cannabis use potentially impacting developmental trajectories. Here, we comprehensively assess the influence of adolescent cannabis use onset on neurocognitive trajectories and consider how recent delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) may influence neurocognition. We use the large, diverse longitudinal A…

Comorbidity between post-traumatic stress disorder (PTSD) and alcohol use is common and mutually-reinforcing, yet there are no pharmacological strategies that specifically target trauma-linked escalation of alcohol intake. We evaluated whether 3,4-methylenedioxymethamphetamine (MDMA), given in a therapy-adjunctive fashion (30 min before fear extinction), could facilitate extinction of conditioned…

Afflicting over 50 million people worldwide and demonstrating growing global trends of abuse, amphetamine-type stimulant abuse poses a significant public health burden. No effective pharmacological treatments exist for amphetamine-type stimulant use disorders, underscoring a critical need to identify novel, effective therapeutic targets. Amphetamine exerts its actions in part by targeting high-af…

Cocaine use disorder is characterized by persistent relapse vulnerability, which escalates with prolonged withdrawal. Corticostriatal circuits are key substrates for relapse, yet the role of the secondary motor cortex (M2) and its distinct projections to the dorsolateral striatum (DLS) and dorsomedial striatum (DMS) remains poorly understood. Here, we combined intravenous self-administration, pat…

Previous work showed that rats that were exposed to a high-fat, low-carbohydrate/protein ketogenic diet (KD) exhibited elevated blood alcohol levels following alcohol exposure compared with rats fed regular chow. Additionally, the administration of a KD prior to alcohol exposure (i.e., a history of KD) reduced alcohol consumption in alcohol-dependent rats that were no longer on the diet. In the p…