Effects of postweaning administration of delta-9-tetrahydrocannabinol (THC) on adult behavioral and neuroendocrine function in Sprague-Dawley and Fischer-344 rats.

Abstract

Delta-9-tetrahydrocannabinol (THC) was administered to young male Fischer-344 (CDF) and Sprague-Dawley (CD) rats on days 30-50 of age. Doses of THC consisted of 20, 10 or 5 doses of 10 mg/kg spaced over the 20-day period. On day 140 animals were exposed to a 15 sec 1.5 mA scrambled foot-shock. Latency for withdrawal from 55 degrees C water was used as a measure for analgesia. Both CDF and CD rats showed a foot-shock induced analgesia (FSIA). Animals which had received 5 or 10 doses of THC in youth showed an enhanced response to foot-shock in the CDF rat. The foot-shock was then paired with an unconditioned stimulus (shock environment) and a conditioned analgesia developed over 4 days. At weekly intervals thereafter animals were tested in the shock environment only for extinction of the analgesic response. Over 4 weeks, analgesia did not show extinction in the CDF rat. Extinction of the response was observed in the veh and 20 dose groups in the CD rat; whereas a resistance to extinction was observed in the other groups. The CDF rats were then sacrificed following the last extinction trial and serum corticosterone and prolactin measured. Five and 10 doses of THC decreased prolactin levels; stress, however, increased these levels above the levels in VEH treated animals exposed to stress. Extinction of a fixed ratio 10 as well as exposure to fixed ratio strain in the CD rat were not affected by THC. These data suggest that THC administered during postweaning development alters endogenous systems which mediate the animals response to stress.