Neuropsychopharmacology

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…

N-methyl-D-aspartate receptors (NMDARs) in the prefrontal cortex (PFC) are critical regulators of neuronal excitability, synaptic plasticity, and cognitive function. NMDAR disruptions, including pharmacological blockade and anti-NMDAR encephalitis, can mimic symptoms of schizophrenia. These observations support the glutamate hypothesis of schizophrenia, which posits that symptoms arise from abnor…

Kappa opioid receptor agonists are clinically used to treat pruritus and have therapeutic potential for the treatment of pain and neuropsychiatric disorders. We have previously shown that triazole 1.1 is a G protein signaling-biased KOR agonist, that can suppress itch without producing signs of sedation in mice. This profile was recapitulated in rats and non-human primates; however, triazole 1.1 …

Pleasure plays a crucial role in positive reinforcement and motivation. Brain regions able to amplify positive hedonic reactions to sweetness, known as 'hedonic hotspots', are distributed within the mesocorticolimbic reward systems. The olfactory tubercle (OT), a part of the ventral striatum that receives olfactory input, contains distinct functional domains: the anteromedial domain mediates appr…