Effects of pharmacological and environmental manipulations on choice between fentanyl and shock avoidance/escape in male and female rats under mutually exclusive and non-exclusive choice conditions.

Substance use disorders are defined by persistent drug consumption despite adverse consequences. Accordingly, we developed two fentanyl-vs-shock avoidance/escape choice procedures in which male and female rats responded under a fixed-ratio (FR)1:FR1 concurrent schedule of shock avoidance/escape and IV fentanyl under either mutually exclusive or non-exclusive choice conditions. Initial experiments using a discrete-trial procedure determined behavioral allocation between mutually exclusive shock avoidance/escape and different fentanyl doses (0.

Adolescent social housing protects against adult emotional and cognitive deficits and alters the PFC and NAc transcriptome in male and female C57BL/6J mice.

Introduction: Adolescence is a critical period in cognitive and emotional development, characterized by high levels of social interaction and increases in risk-taking behavior including binge drinking. Adolescent exposure to social stress and binge ethanol have individually been associated with the development of social, emotional, and cognitive deficits, as well as increased risk for alcohol use disorder. Disruption of cortical development by early life social stress and/or binge drinking may partly underlie these enduring emotional, cognitive, and behavioral effects.

Effects of environmental and pharmacological manipulations on cocaine-vs-negative reinforcer choice in male and female rats.

Rationale: The adverse consequences of human addictive drug use could be the result of either addictive drug consumption resulting in punishment (e.g., incarceration) or failure to engage in negative-reinforced behaviors that might compete with drug-maintained behaviors (e.

A concurrently available negative reinforcer robustly decreases cocaine self-administration in male and female rats.

Continued drug-taking despite adverse consequences is hypothesized to be an insidious behavioral hallmark of drug addiction. Although most preclinical research has focused on drug self-administration in the presence of positive punishment, another source of potential adverse consequences is behavioral allocation away from negative reinforcers (i.e.

Preclinical Characterization and Development on NAQ as a Mu Opioid Receptor Partial Agonist for Opioid Use Disorder Treatment.

Mu opioid receptor (MOR) selective antagonists and partial agonists have clinical utility for the treatment of opioid use disorders (OUDs). However, the development of many has suffered due to their poor pharmacokinetic properties and/or rapid metabolism. Our recent efforts to identify MOR modulators have provided 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3-carboxamido)morphinan (NAQ), a low-efficacy partial agonist, that showed sub-nanomolar binding affinity to the MOR ( 0.

Sensitivity of a fentanyl-vs.-social interaction choice procedure to environmental and pharmacological manipulations.

Recent studies have shown that social interaction can serve as an alternative reinforcer to opioid self-administration under a choice context in rats. However, additional parametric studies are needed to evaluate the sensitivity of opioid-vs.-social interaction procedures relative to more established opioid-vs.

Effects of environmental manipulations on cocaine-vs-social choice in male and female rats.

Cocaine use disorder occurs in an environment where cocaine and other nondrug commodities are concurrently available. Preclinical drug-vs-nondrug choice procedures are one simplified method of modeling this complex clinical environment. The present study established a discrete-trial cocaine-vs-social interaction choice procedure in male and female rats and determined sensitivity of choice behavior to manipulations of reinforcer magnitude and non-contingent "sample" reinforcer presentation.

Modulation of heroin intake by ovarian hormones in gonadectomized and intact female rats.

Rationale: Heroin intake decreases during the proestrus phase of the estrous cycle in female rats. Circulating concentrations of both estradiol and progesterone peak during proestrus, and it is not known which of these hormones, or their combination, are responsible for these effects.

Objectives: The purpose of this study was to determine the effects of estradiol, progesterone, and their combination on heroin self-administration in female rats.

Absence of effects of intermittent access to alcohol on negative affective and anxiety-like behaviors in male and female C57BL/6J mice.

Alcohol use disorder is highly comorbid with other neuropsychiatric disorders such as depression and anxiety. Importantly, women and men are affected differentially by heavy drinking, with women experiencing longer negative affective states after intoxication and increased likelihood to present with comorbid mood or anxiety disorders. In rodents, several studies using different alcohol administration models have shown the development of depressive-like or anxiety-like phenotypes that emerge during abstinence.