MATERNAL EXPOSURE TO DELTA(9)-TETRAHYDROCANNABINOL FACILITATES MORPHINE SELF-ADMINISTRATION BEHAVIOR AND CHANGES REGIONAL BINDING TO CENTRAL MU-OPIOID RECEPTORS IN ADULT OFFSPRING FEMALE RATS

Opiates and cannabinoids are among the most widely consumed habit-form ing drugs in humans, Several studies have demonstrated the existence o f interactions between both kind of drugs in a variety of effects and experimental models. The present study has been focused to determine w hether perinatal Delta(9)-tetrahydrocannabinol (Delta(9)-THC) exposure affects the susceptibility to reinforcing effects of morphine in adul thood and whether these potential changes were accompanied by variatio ns in mu opioid receptor binding in brain regions related to drug rein forcement. Adult female rats born from mothers that were daily treated with Delta(9)-THC during gestation and lactation periods, exhibited a statistically significant increase in the rate of acquisition of intr avenous morphine self-administration behavior when compared with femal es born from vehicle-exposed mothers, an effect that did not exist in Delta(9)-THC-exposed male offspring, This increase was significantly g reater on the last day of acquisition period. There were not significa nt differences when the subjects were lever pressing for food. In para llel, we have also examined the density of mu opioid receptors in the brain of adult male and female offspring that were exposed to Delta(9) -THC during the perinatal period. Collectively, perinatal exposure to Delta(9)-THC produced changes in mu opioid receptor binding that diffe red regionally and that were mostly different as a function of sex. Th us, Delta(9)-THC-exposed males exhibited a lower density for these rec eptors than their respective oil-exposed controls in the caudate-putam en area as well as in the amygdala (posteromedial cortical nucleus). O n the contrary, Delta(9)-THC-exposed females exhibited higher density of these receptors than their respective oil-exposed controls in the p refrontal cortex, the hippocampus (CA3 area), the amygdala (posteromed ial cortical nucleus), the ventral tegmental area and the periaqueduct al grey matter, whereas the binding was lower than control females onl y in the lateral amygdala. These results support the notion that perin atal Delta(9)-THC exposure alters the susceptibility to morphine reinf orcing effects in adult female offspring, in parallel with changes in mu opioid receptor binding in several brain regions. (C) 1998 Elsevier Science B.V. All rights reserved.