Abstract

Intravenous self-administration of heroin in an animal model of internalizing vs externalizing temperament

Emery MA, Parsegian A, Maras PM, Hebda-Bauer EK, Flagel SB, Watsons SJ, Akil H
50th Annual Meeting of the Society for Neuroscience, Virtual. 2021.

Abstract

In humans, only a small portion of those who experiment with recreational drug use transition to a substance use disorder (SUD). Multiple factors are thought to underlie this susceptibility, including differences in temperament. Those with externalizing temperaments are hypothesized to approach drugs of abuse from a sensation-seeking pathway, while those with internalizing temperaments appear less likely to approach drugs of abuse for purely recreational reasons but rather in response to other triggers such as psychosocial stress. Our lab has used a selective breeding strategy based on degree of exploratory locomotion in a novel environment to derive two lines of rats with distinct behavioral and neurobiological phenotypes, termed selectively-bred high-responders (bHRs) and low-responders (bLRs). We have previously shown that temperamental differences between these rats determines their propensity to seek and take psychostimulant drugs. Specifically, bHRs, who display a sensation-seeking phenotype, demonstrate a higher basal propensity to take drugs; whereas bLRs appear less susceptible at baseline but will seek and take drugs in response to psychosocial stress. While we have shown that bHRs and bLRs have biological differences in endogenous opioid system, such as differential expression levels of mu opioid receptor, we had not examined bHR/bLR differences in intravenous self-administration of opioids. Here, we used a free access self-administration paradigm of diacetylmorphine (heroin) to determine whether these individual differences impact self-administration of opioids. We observed the expected phenotype differences at baseline where bLRs seek and take less drug, replicating the pattern seen with psychostimulants. Interestingly, a small but potentially important sex x genotype interaction has emerged where female bHRs sought and took more heroin than males, a pattern not observed for bLRs. Future experiments will elaborate on this sex difference, as well as exploring the impact of stress on heroin self-administration. These findings contribute to our understanding of the impact of individual differences as well as a potential interaction between biological sex and temperament upon the trajectory of opioid addiction development.