No abstract

Subchronic PCP administration results in a specific hypermethylation in the Pvalb promoter which may contribute to parvalbumin deficits in this animal model of psychosis.

No abstract

No abstract

In the current study we investigated the efficacy of donepezil, risperidone and selective nicotinic α7 and α4β2 receptor agonists to reverse a delay-induced deficit in recognition memory. Adult female hooded-Lister rats received drug treatments and were tested in the novel object recognition (NOR) task following a 6 hour inter-trial interval (ITI). In all treatment groups there was no preference for the left or right identical objects in the acquisition trial. In the retention trial vehicle, risperidone (0.16mg/kg), PNU-282987, an α7 agonist (5mg/kg) and RJR-2403, an α4β2 agonist (1mg/kg) treated rats were unable to discriminate between the novel and familiar objects following a 6 hour ITI. In contrast, donepezil (1.0mg/kg), PNU-282987 (10mg/kg) and RJR-2403 (0.1mg/kg) treated rats spent significantly more time exploring the novel compared to the familiar object following the 6 hour ITI, indicative of enhanced cognitive performance (P<0.05-P<0.01). Interestingly, these compounds were efficacious when administered either before the acquisition or the retention trial of the task, suggesting an important role for nicotinic receptor subtypes in the formation and retrieval of recognition memory.

No abstract

No abstract

BackgroundOpioid withdrawal is a key driver of opioid addiction and an obstacle to recovery. However, withdrawal effects on opioid reinforcement and mesolimbic neuroadaptation are understudied and the role of sex is largely unknown.MethodsMale (n=10) and female (n=9) rats responded under a fentanyl-vs.-food “choice” procedure during daily 2h sessions. In addition to the daily choice sessions, rats were provided extended access to fentanyl during 12h sessions. After two weeks of this self-administration regimen, the nucleus accumbens (NAc) and ventral tegmental area (VTA) of a subset of rats were subjected to RNA sequencing. In the remaining rats, a third week of this self-administration regimen was conducted, during which methadone effects on fentanyl-vs.-food choice were determined.ResultsPrior to opioid dependence, male and female rats similarly allocated responding between fentanyl and food. Abstinence from extended fentanyl access elicited a similar increase in somatic withdrawal signs in both sexes. Despite similar withdrawal signs and extended access fentanyl intake, opioid withdrawal was accompanied by a maladaptive increase in fentanyl choice in males, but not females. Behavioral sex differences corresponded with transcriptional hyperfunction in the NAc and VTA of opioid-withdrawn females relative to males. Methadone blocked withdrawal-associated increases in fentanyl choice in males, but failed to further decrease fentanyl choice in females.ConclusionsThese results provide foundational evidence of sex-specific neuroadaptations to opioid withdrawal, which may be relevant to the female-specific resilience to withdrawal-associated increases in opioid choice and aid in the identification of novel therapeutic targets.