Neuroleptic-induced changes in the anxiolytic and myorelaxant properties of diazepam in the rat

Diazepam (2.0 mg/kg) was injected (IP) into rats 30 min before chlorpromazine (2.5, 5.0, or 10.0 mg/kg) on ten occasions. All doses of chlorpromazine enhanced the capacity of diazepam to increase rats' exploration of the exposed arms of an elevated plus-maze, an animal screening test for anxiolytic and anxiogenic substances. When maze testing occurred during each of the ten diazepam----chlorpromazine trials (after diazepam but before chlorpromazine), this enhancement effect appeared on Trial 6 and persisted thereafter. Haloperidol (3.0 mg/kg, IP) changed diazepam-elicited plus-maze activity in the same manner as chlorpromazine; however, thioridazine (10.0 mg/kg) and pimozide (2.0 mg/kg) were ineffective. Additionally, haloperidol, like chlorpromazine, was found to reduce diazepam's muscle relaxation effect (inclined plane test) as a consequence of diazepam----haloperidol pairings; once again, thioridazine and pimozide proved ineffective. These results suggested that not all neuroleptics will alter diazepam activity, and also that dopamine blockade per se is not sufficient to induce such changes. While the reasons for the enhanced plus-maze effects of diazepam induced by haloperidol and chlorpromazine remain elusive, the diminished myorelaxant effect may be linked to a neuroleptic's capacity to induce muscular side effects: thioridazine and pimozide are far less likely to yield such effects than are chlorpromazine and haloperidol. Haloperidol administered chronically by itself was found to have an effect on diazepam-induced myorelaxation. Administration of this butyrophenone either orally (2.0 mg/kg daily for 22 days) or in depot form (haloperidol decanoate, 60.0 mg/kg IM once a month for four months) caused a diminished effect of diazepam in rats subjected to the inclined plane test.(ABSTRACT TRUNCATED AT 250 WORDS)