Repeated testing of rats markedly enhances the duration of effects induced by haloperidol on treadmill locomotion, catalepsy, and a conditioned avoidance response

Abstract

In the present experiments we have investigated the duration of haloperidol-induced effects in rats tested repeatedly, and in rats tested on a single occasion after drug administration. The behavioral test situations used include treadmill locomotion (speed 4 m/min), inclined grid catalepsy, two-way conditioned avoidance behavior and open field spontaneous locomotor activity. It was found that the duration of haloperidol-induced effects on treadmill locomotion, spontaneous locomotor activity, catalepsy and a conditioned avoidance response (doses: 0.32, 0.32, 1.25 and 0.2 mg/kg IP, respectively) was about 2 hr or less in animals observed once only (“independent procedure”). With the possible exception for locomotor activity, the duration of haloperidol-induced effects was considerably prolonged, up to 8 hr depending on the test situation, in animals observed repeatedly after the administration of haloperidol in the same doses (“dependent procedure”). The enhanced duration by the dependent procedure is probably not caused by handling stress since the enhanced duration of haloperidol-induced effects in some of the behavioral tests were only noted in animals tested repeatedly in one particular test, and not in animals given the repeated pretests in another situation. Furthermore, it was not possible to relate the enhanced duration of haloperidol-induced effects by repeated testing to changes in striatal DA metabolism as evaluated by measurements of DOPAC, HVA and DA. It was found that the treadmill test 2–4 hr after haloperidol (0.12–0.32 mg/kg IP), at certain doses and time intervals produced an increase in DA turnover [(DOPAC + HVA)/DA], but this increase was the same in both procedures (dependent and independent). Our findings that the time-course of action of haloperidol is dependent on the test procedures used may be of importance when interpreting interaction studies and the relationship between pharmacokinetics and behavioral effects of this, and possible other, psychotropic drugs.