Acquisition of remifentanil self-administration: Enhanced in female rats but no effect of adolescent stress exposure

Animal models of acquisition have been vital in shaping our understanding of vulnerability factors that influence susceptibility to drugs of abuse. Decades of research substantiates a number of biological, environmental, and behavioral factors that predict vulnerability – many of which have been important in the development of early intervention efforts in humans. The goal of the present study was to examine the acquisition of a synthetic opioid derivative in 66 adult male and female Long-Evans rats following histories of stress exposure during adolescence. Stress-exposed rats were subjected to a mild stress paradigm, which included alternating exposure to synthetic fox feces and physical restraint for eight days. Following stress induction and assessment, all rats were implanted with intravenous catheters in order to self-administer remifentanil (1 μm/kg/infusion) with no prior operant training. Acquisition of remifentanil self-administration was measured over 15 days. Findings indicate that regardless of stress condition, female rats acquired remifentanil self-administration sooner and emitted more active lever presses than males. Stress exposed animals exhibited increased anxiety-like response compared to the control group following exposure to stress, operationalized as decreased exploratory behavior on an Elevated Plus Maze. However, these effects were not expressed as significant differences in self-administration by stress. Together, these findings indicate that sex differences are evident in remifentanil self-administration. •We provide a novel way of analyzing drug acquisition in self -administration models•Female animals were faster to acquire remifentanil self-administration•Exposure to mild stress elicited higher, and more chronic levels of anxiety.