Strain dependence of adolescent Cannabis influence on heroin reward and mesolimbic dopamine transmission in adult Lewis and Fischer 344 rats

Adolescent ?9-tetrahydrocannabinol (THC) exposure induces behavioral sensitization to opiates in Sprague-Dawley rats, consistent with the hypothesis that Cannabis is a gateway for opiate abuse. To investigate the role of inbred strains differences, we studied the long lasting effects of adolescent THC exposure on reward, cognitive and emotional function in addiction prone Lewis and addiction resistant Fischer344 rats. Lewis and Fischer344 rats were exposed to THC during adolescence and at adulthood DA transmission responsiveness to THC and heroin in the accumbens shell and core was monitored by microdialysis and heroin reward was studied by conditioned place preference (CPP) and heroin priming. Cognitive and emotional functions were studied by object recognition, Y maze and elevated plus maze tests. THC stimulated shell DA in Lewis but not in Fischer344 rats. Adolescent THC exposure potentiated DA response to heroin in Lewis shell and core and only in the core of Fischer344 rats. Control Lewis rats developed stronger CPP to heroin and resistance to extinction compared to Fischer344 strain. In Lewis THC exposure did not affect heroin CPP but potentiated the effect of heroin priming. In Fischer344 THC exposure increased heroin CPP and made it resistant to extinction. Lewis showed craving-like reactions during extinction and hedonic reactions in response to heroin priming. Moreover adolescent THC exposure affected emotional function only in this strain. These observations suggest that long-term effects of Cannabis exposure on heroin addictive liability and emotionality are dependent on individual genetic background.