Increased self-administration of cocaine following haloperidol: effect of ovariectomy, estrogen replacement, and estrous cycle.

Rats which have been trained to self-administer cocaine intravenously show a dose-dependent increase in drug intake when pretreated with dopamine antagonists. This neuroleptic-induced increase in cocaine intake may be related to the antipsychotic potency and suggests that self-administration behavior may provide a useful model for evaluating neuroleptic activity. The present study examines the influence of ovarian hormones on the potency of the neuroleptic haloperidol using the cocaine self-administration model. It was found that the potency of haloperidol fluctuated across the estrous cycle with subjects in diestrus self-administering more cocaine than animals tested in estrus or proestrus. It was also demonstrated that the potency of haloperidol was reduced significantly following ovariectomy (OVX), however this OVX-induced attenuation could not be reversed with a number of estrogen or catechol-estrogen treatments. To the extent that the self-administration model can reflect the potency of antipsychotic drugs, these data indicate that ovarian function can affect neuroleptic activity, although the hormone(s) involved remain unclear. The clinical implications of these data underscore the need to further examine the influence of female sex hormones on the therapeutic efficacy of antipsychotic drugs.