Susceptibility to sensitization. II. The influence of gonadal hormones on enduring changes in brain monoamines and behavior produced by the repeated administration of D-amphetamine or restraint stress.

Repeated amphetamine use produces an enduring sensitization of brain dopamine (DA) systems and behavior. Repeated exposure to stress can also produce sensitization, and amphetamine and stress may be interchangeable in this regard. There is, however, enormous individual variation in the susceptibility to sensitization by either stimulants or stress. The purpose of the present study was to determine if endogenous gonadal hormones contribute to individual variation in the sensitization of stereotyped behaviors, locomotion or regional brain monoamine metabolism. It was found that removal of testicular hormones by castration of male rats facilitated the behavioral sensitization produced by either repeated amphetamine treatment or repeated restraint stress, but ovariectomy of female rats was without effect. Prior exposure to amphetamine enhanced striatal homovanillic acid (HVA) levels and dihydroxyphenylacetic acid to DA and HVA to DA ratios in intact female, ovariectomized female and castrated male rats, but not gonadally-intact male rats. As a group, intact males were particularly heterogeneous because they were divisible into two neurochemically distinct subgroups based on their degree of behavioral sensitization, and the other groups were not. It is suggested that individual differences in the sensitization of brain DA systems and behavior produced by repeated exposure to amphetamine or stress may be due in part to individual differences in the concentration of a testicular hormone.