The interaction of delta‐9‐tetrahydrocannabinol (THC) and estradiol during adolescence has long‐term effects on the repeated acquisition and performance of response sequences in female rats

Abstract

THC abuse by individuals during adolescence may produce long‐term deficits in complex behavioral processes such as learning. Therefore, the present experiment tested the hypothesis that 40 daily THC injections of 5.6 mg/kg i.p. during adolescence in ovariectomized (+OVX) or sham‐operated (‐OVX) female rats would alter THC's disruptive effects on response rate and accuracy as adults. Following THC administration and training to respond under a multiple schedule with acquisition and performance components, 4 groups received 0.56‐10 mg/kg of THC acutely. With respect to response rate, THC produced similar dose‐dependent effects in both the acquisition and performance components, although +OVX had higher overall baseline rates than ‐OVX. With respect to accuracy, THC's effects differed across components and adolescent treatments. In the acquisition components, +OVX subjects had higher baseline error levels than ‐OVX subjects. The rank order for disruption by THC was ‐OVX/ +THC > +OVX/‐THC > ‐OVX/‐THC = +OVX/+THC. In the performance components, there were no baseline differences between groups and THC had little or no effect on accuracy at any dose. These results indicate that adolescent THC administration in female rats can have long‐term effects on their capacity to learn, and that these effects cannot be readily predicted from the effects of THC on response rate or on performance tasks. Supported by DA 019625.