Influence of genotype in the long lasting effects of adolescence cannabis exposure on reward and emotional functions

Epidemiological studies suggest that genetic factors play an important role in drug addiction. Moreover adolescent Cannabis exposure has been hypothesized to function as a gateway to opiate abuse. The demonstration of cross-sensitization between cannabinoids and opiates has been viewed as a possible neurobiological mechanism underlying this phenomenon. However available data would suggest that previous exposure to cannabinoids reduces sensitivity to opiates reward at variance with what posited by the Gateway Hypothesis. Therefore we hypothesized that the adaptive changes induced by Cannabis pre-exposure could be also genetically controlled. Moreover since adolescence Cannabis use has been reported to affect cognitive function and emotionality at adulthood we investigated further this issue. We used a genetic animal model of vulnerability to drugs of abuse (Fischer 344, and Lewis rats). We will show that adolescence exposure to the active component of Cannabis (9-tetrahydrocannabinol,THC) induces different adaptive changes in dopamine mesolimbic transmission in the two genotypes. Results from the more vulnerable strain (Lewis) are indicative of an increased rewarding effect of heroin at adulthood as estimated by brain microdialysis and conditioned place preference. While cognitive function at adulthood appears not affected by adolescence THC exposure, emotional function is selectively changed in the LEW strain