PERINATAL DELTA(9)-TETRAHYDROCANNABINOL EXPOSURE REDUCES PROENKEPHALIN GENE-EXPRESSION IN THE CAUDATE-PUTAMEN OF ADULT FEMALE RATS

Perinatal Delta(9)-tetrahydrocannabinol (Delta(9)-THC) exposure in rat s affects several behavioral responses, such as opiate self-administra tion behavior or pain sensitivity, that can be directly related to cha nges in opioidergic neurotransmission. In addition, we have recently r eported that the administration of naloxone to animals perinatally exp osed to Delta(9)-THC produced withdrawal responses, that resemble thos e observed in opiate-dependent rats. The purpose of the present study was to examine the basal opioid activity in the brain of adult male an d female rats that had been perinatally exposed to Delta(9)-THC. To th is aim, proenkephalin mRNA levels were measured, by using in situ hybr idization histochemistry, in the caudate-putamen, nucleus accumbens, c entral amygdala and prefrontal cingulate cortex. The results showed a marked reduction in proenkephalin mRNA levels in the caudate-putamen o f Delta(9)-THC-exposed females as compared to oil-exposed females, whe reas no changes were observed between Delta(9)-THC- and oil-exposed ma les. There were no differences in proenkephalin mRNA levels in the nuc leus accumbens, central amygdala and prefrontal cingulate cortex betwe en males and females perinatally exposed to Delta(9)-THC and their res pective controls, although a certain trend to decrease was observed in Delta(9)-THC-exposed females. In summary, perinatal exposure to Delta (9)-THC exposure decreased proenkephalin gene expression in the caudat e-putamen of adult rats, although this effect exhibited a marked sexua l dimorphism since it was only seen in females. This result is in agre ement with a previous observation fi om our laboratory that females, b ut not males, that had been perinatally exposed to Delta(9)-THC, self- administered more morphine in adulthood. This suggests that low levels of proenkephalin mRNA may be used as a predictor of greater vulnerabi lity to opiates.