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Biology subjects

Ellis, A. S.

Publications and source records attributed to Ellis, A. S..

2 recordsLinked to original sources

Paternal morphine exposure enhances morphine self-administration and induces region-specific neural adaptations in reward-related brain regions of male offspring

BackgroundA growing body of preclinical studies report that preconceptional experiences can have a profound and long-lasting impact on adult offspring behavior and physiology. However, less is known about paternal drug exposure and its effects on reward sensitivity in the next generation. MethodsAdult male rats self-administered morphine for 65 days; controls received saline. Sires were bred to drug-naive dams to produce first-generation (F1) offspring. Morphine, cocaine, and nicotine self-administration were measured in adult F1 progeny. Molecular correlates of addiction-like behaviors were measured in reward-related brain regions of drug naive F1 offspring. ResultsMale, but not female offspring produced by morphine-exposed sires exhibited dose-dependent increased morphine self-administration and increased motivation to earn morphine infusions under a progressive ratio schedule of reinforcement. This phenotype was drug-specific as self-administration of cocaine, nicotine, and sucrose were not altered by paternal morphine history. The male offspring of morphine-exposed sires also had increased expression of mu-opioid receptors in the ventral tegmental area but not in the nucleus accumbens. ConclusionsPaternal morphine exposure increased morphine addiction-like behavioral vulnerability in male but not female progeny. This phenotype is likely driven by long-lasting neural adaptations within the reward neural brain pathways.

neuroscience↗

Adolescent Social Isolation Increases Vulnerability to Cocaine.

Childhood and adolescent adversity is associated with a wide range of psychiatric disorders, including an increased risk for substance abuse. Despite this, the molecular mechanisms underlying how chronic stress during adolescence alters reward signaling remains largely unexplored. Understanding how adolescent stress increases addiction-like phenotypes could inform the development of targeted interventions both before and after drug use. The current study examined how adolescent-onset isolation stress affected behavioral, molecular, and physiological responses to cocaine in male and female mice. Adolescent-onset social isolation did not alter the ability of mice to learn an operant response for food, nor influence food self-administration or motivation for food on a progressive ratio schedule. However, male and female socially stressed mice exhibited an increase in motivation for cocaine and cocaine seeking during a cue-induced reinstatement session. Additionally, we demonstrated that adolescent-onset social isolation increased cocaine-induced neuronal activation, as assessed by Fos expression, within the nucleus accumbens core and shell, ventral pallidum, dorsal bed nucleus of the stria terminalis, lateral septum and basolateral amygdala. Taken together, the present studies demonstrate that social stress during adolescence augments the behavioral responses to cocaine during adulthood and alters the responsiveness of reward-related brain circuitry.

neuroscience↗