Biomaterial Database

Paternal morphine exposure enhances morphine self-administration and induces region-specific neural adaptations in reward-related brain regions of male offspring. 2023

Andre B Toussaint, and Alexandra S Ellis, and Angela R Bongiovanni, and Drew R Peterson, and Charlotte C Bavley, and Reza Karbalaei, and Hannah L Mayberry, and Shivam Bhakta, and Carmen C Dressler, and Caesar G Imperio, and John J Maurer, and Heath D Schmidt, and Chongguang Chen, and Kathryn Bland, and Lee-Yuan Liu-Chen, and Mathieu E Wimmer

Department of Psychology, Program in Neuroscience Temple University, Philadelphia, PA, USA.

A 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. Adult male rats self-administered morphine for 65 days; controls received saline. Sires were bred to drug-naïve 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 naïve F1 offspring. Male, 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. Paternal 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.