SEXUAL DIMORPHIC EFFECTS OF CHRONIC PHENCYCLIDINE IN RATS

The behavioral effects of phencyclidine (PCP) were studied in male and female Sprague-Dawley rats to determine if chronic infusions would re sult in sexually dimorphic effects. Rats were trained to make operant responses for food during 30-min response periods that occurred 4 time s each day. After attaining stable baseline behaviors, 10 mg of PCP/kg /day was infused s.c. for 10 days. Females were more profoundly affect ed than males. In the females, response rates were suppressed to 30-71 % of control rates during the first 7 days of infusion. In contrast, r esponse rate in male rats never fell below 77% of control during the i nfusion period. By the eighth infusion day both sexes had become toler ant to these behavioral effects. After stopping infusions there was cl ear evidence that behavioral dependence had developed; however, the ab stinence effects in males and females were similar. Saturation studies of [H-3]dizocilpine (MK-801; ,11-dihydro-5H-dibenzo[a,d]cyclohepten-5 ,10-imine) binding to brain membranes were conducted to determine if t here were sex-dependent receptor differences. There were no significan t differences in K-d +/- S.D. (7.6 +/- 1.5 and 7.1 +/- 0.9 nM for male s and females, respectively) or B-max +/- S.D.(4.1 +/- 0.2 and 4.0 +/- 0.5 pmol/mg protein for males and females, respectively).