Paternal exposure to morphine during adolescence induces reward-resistant phenotype to morphine in male offspring

The developing brain is extremely sensitive to drugs during adolescence. The devastating impacts of opioid abuse in this critical period not only do involve individuals but also are witnessed in the subsequent generations. Therefore, what is recognized as the population susceptible to the effects of opioid abuse could be much greater in number. In this study, we explored the transgenerational effects of morphine exposure in adolescent stage on morphine reward in male offspring through the patriline. Male Wistar rats underwent 10 days of incremental doses of morphine administration during adolescence; the broad spectrum of neurobehavioral alterations in rat adolescence is akin to that of human adolescence. Thereafter, following a 20-day wash-out period, adult males copulated with naive females. The adult male offspring were examined for morphine (0, 1, 2 and 5 mg/kg)-induced conditioned place preference (CPP). Moreover, the spontaneous activity of ventral tegmental area (VTA) dopamine (DA) neurons was investigated utilizing extracellular single-unit recording technique. Our results demonstrated that paternal morphine exposure prior to conception leads to the development of a tolerance to the rewarding effects of morphine at the low dose of 1 mg/kg (rightward shift in dose-effect curve). Furthermore, morphine-sired rats elicited a decrease in spontaneous burst firing of VTA DA neurons (burst event frequency, bursting activity and burst duration) compared to saline-sired ones. Hence, our study has provided evidence that paternal morphine exposure during adolescence alters the rewarding effects of morphine in male offspring. This effect may be mediated in part by a decrease in phasic activation of VTA DA neurons.