Sex-specific transgenerational effects of adolescent morphine exposure on short-term memory and anxiety behavior: Male linage.

Current estimates indicate that opioid use and misuse are a rising epidemic, which presents a substantial socioeconomic burden around the world. Chronic opioid consumption, specifically during the critical period of adolescence, can lead to enduring effects not only in individuals but also in future generations. Utilizing rodent model, we have previously reported the impacts of paternal exposure to chronic morphine during adolescence on neurobehavioral features in progenies. Currently, the potential transgenerational effects of paternal morphine exposure during adolescence on anxiety-like behavior and short-term memory remains unknown. Male Wistar rats were exposed to increasing doses of morphine for ten days in adolescence (PND 30-39). Thereafter, following a 30-days drug-free period, the treated male rats mated with naïve females. The anxiety-like behavior and short-term memory performance were assessed in adult male and female offspring (PND 60) using open field and Y-maze tests. Both male and female progenies of morphine-treated sires revealed a significant reduction in the movement velocity compared to progenies of saline-treated sires as measured by open field test. Morphine-sired male but not female offspring also showed a non-significant large decreasing effect on time spent in the center and frequency of entries to the center of open field box. Moreover, a significant reduction in the number of entries and percent of time spent in the novel arm was observed in male and female morphine-sired offspring, as measured using Y-maze test. Growth outcomes also did not demonstrate any difference in the number of dam's fertility, pups birth, and death between morphine-sired and saline-sired groups in both sexes. Collectively, paternal exposure to morphine during adolescence induces sex-specific and selective disturbances in short-term memory while anxiety-like behavior was slightly disturbed.