Adolescent Female Cannabinoid Exposure Diminishes the Reward-Facilitating Effects of Δ9-Tetrahydrocannabinol and d-Amphetamine in the Adult Male Offspring

George Pitsilis, Dimitrios Spyridakos, George G. Nomikos, George Panagis

Marijuana is currently the most commonly abused illicit drug. According to recent studies, cannabinoid use occurring prior to pregnancy can impact brain plasticity and behavior in future generations. The purpose of the present study was to determine whether adolescent exposure of female rats to Δ(9)-tetrahydrocannabinol (Δ(9)-THC) induces transgenerational effects on the reward-facilitating effects of Δ(9)-THC and d-amphetamine in their adult male offspring. Female Sprague-Dawley rats received Δ(9)-THC (0.1 or 1 mg/kg, i.p.) or vehicle during postnatal days 28-50. As adults, females were mated with drug-naïve males. We then assessed potential alterations of the Δ(9)-THC's (0, 0.1, 0.5, and 1 mg/kg, i.p.) and d-amphetamine's (0, 0.1, 0.5, and 1 mg/kg, i.p.) reward-modifying effects using the curve-shift variant of the intracranial self-stimulation (ICSS) procedure in their adult male F1 offspring. The reward-facilitating effect of the 0.1 mg dose of Δ(9)-THC was abolished in the F1 offspring of females that were exposed to Δ(9)-THC (0.1 or 1 mg/kg), whereas the reward-attenuating effect of the 1 mg dose of Δ(9)-THC remained unaltered. The reward-facilitating effects of 0.5 and 1 mg of d-amphetamine were significantly decreased in the F1 offspring of females that were exposed to Δ(9)-THC (1 mg/kg and 0.1 or 1 mg, respectively). The present results reveal that female Δ(9)-THC exposure during adolescence can diminish the reward-facilitating effects of Δ(9)-THC and d-amphetamine in the adult male offspring. These transgenerational effects occur in the absence of in utero exposure. It is speculated that Δ(9)-THC exposure during female adolescence may affect neural mechanisms that are shaping reward-related behavioral responses in a subsequent generation, as indicated by the shifts in the reward-facilitating effects of commonly used and abused drugs.