Differences in behavioral response to morphine in a genetic model of temperament

Emery MA, Aydin C, Hebda-Bauer EK, Maras PM, Parsegian A, Stefanov AV, Tang A, Watson SJ, Akil H
Society for Neuroscience. 2019.


Our lab has developed a genetic model of temperament using a selective breeding strategy based on degree of locomotor response in a novel environment. Using this strategy, we have generated and maintain two lines of rats with distinct behavioral and neurochemical phenotypes, termed selectively-bred high-responders (bHRs) and low-responders (bLRs). Our prior work using these lines have demonstrated that their temperamental differences affect their propensity to seek and take psychostimulant drugs. Specifically, bHRs demonstrate a higher basal propensity to take drugs, due to a broadly sensation-seeking phenotype; whereas bLRs appear less susceptible at baseline but will seek and take drugs in response to psychosocial stress. Further, gene expression studies have revealed broad differences in gene expression levels between these two lines which are likely to mediate the differences in temperament. Notably, gene expression differences include members of the endogenous opioid system in multiple reward-related brain areas. In addition to basal differences in the opioid system, exposure to stress during adolescence alters opioid gene expression differentially between the two lines. However, to date bHR/bLR differences in the response to morphine have not yet been characterized. Here, we characterize behavioral responses of bHR and bLR rats to morphine in a variety of behavioral paradigms, including locomotor sensitization, conditioned place preference, and rate of analgesic tolerance development. In addition, we expand the characterization of basal differences in the expression patterns of opioid system components between these lines. Results reveal strain differences in the behavioral response to morphine. Further, basal differences in the biology of the endogenous opioid system as well as differences in the biological response to morphine administration may, at least in part, mediate these differential behavioral responses. These findings provide a foundation to use this model to probe the genetic and neurobiological antecedents that mediate individual differences in the path to develop and maintain opioid addiction.