Chronic cannabinoid treatment in adolescence attenuates c-Fos expression in nucleus accumbens of adult estrous rats

Chronic cannabinoid exposure during adolescence may negatively impact brain development and alter adult motivation and behavior. We present evidence that treatment with a cannabinoid agonist during adolescence attenuates estrous-mediated expression of c-Fos within the nucleus accumbens of female rats exposed to a male conspecific. Thirty-two female Long-Evans rats were administered either 0.4 mg/kg of CP-55,940 or vehicle on a daily basis between the ages of 35-45 days. When subjects reached adulthood (days 71-76), they were tested within an exposure paradigm designed to invoke sexual motivation without allowing for consummatory behavior. Female subjects were naturally-cycling; half were tested when in behavioral estrus (as determined by vaginal cytology) and half were tested outside of estrus. c-Fos expression was then quantified in multiple brain regions associated with female sexual motivation, in addition to two control regions. Analyses revealed that untreated females showed more c-Fos-positive neurons when estrous (versus non-estrous) within the medial preoptic area of the hypothalamus, the ventromedial hypothalamus, and the nucleus accumbens core and shell. Significant attenuation of this estrous effect was observed within the nucleus accumbens core and shell of drug-treated females. This suggests that adolescent cannabinoid exposure may negatively impact the development and/or function of mesolimbic circuitry. These findings build upon earlier research in our laboratory which indicated that chronic cannabinoid exposure during adolescence persistently attenuates the expression of sexual motivation in female rats and provide a potential neurobiological substrate for those behavioral deficits.