Comparative Analysis of the Effects of Actual Versus Assumed Opioid Experience on the Regulation of Ventral Striatal Opioid Receptor Gene Expression

Rationale: We conducted experiments to assess the effect of prior opioid experience on gene expression changes. We compared the current experimenter-imposed short versus extended-access conditions of opioid self-administration and developed a new quantitative method to determine their effectiveness in identifying the role of opioid experience in regulating opioid receptor expression levels in the ventral striatum (VS) using an oxycodone self-administration/abstinence model. Methods: In this study, male Sprague-Dawley rats (n=36) were trained for 20 days to self-administer oxycodone at 0.1 mg/kg/infusion under short access (n=15, or saline as controls n=3, for 3h/day) or extended access (n=15, or saline as controls n=3, for up to 9h/day). After 31 days of abstinence, the animals were sacrificed, 8and PCR was used to evaluate mu- and kappa-opioid receptor (MOR and KOR) gene expression levels in the ventral striatum (VS). Biochemical/behavioral profiles of short versus extended access conditions were compared using current methods and a new quantitative model based on normal mixtures clustering analysis. Data were analyzed using ANOVA and regression analysis to explore the relationship between opioid experience and VS opioid receptor expression levels Results: Our study found that experimenter-determined grouping was inadequate in representing opioid experience and failed to identify distinct biochemical/behavioral groups. However, our quantitative model identified two distinct biochemical/behavioral types related to experience, revealing significant differences in the relationship between opioid experience and MOR/KOR expression and their interactions. Conclusion: The quantitative model is more sensitive than the current experimenter-determined approach in studying the effect of prior opioid experience on VS opioid receptor gene expression