Neurochemical and Motor Effects of High Dose Haloperidol Treatment: Exacerbation by Tryptophan Supplementation 1

Abstract

The neurochemical and motor effects of a high dose (25 mg/kg) of haloperidol were assessed in male Sprague-Dawley rats. In Experiment 1, this high dose of haloperidol caused dramatic increases in striatal dopaminergic and serotonergic turnover that only returned to control levels 100 hr after injection. In the second experiment, the same dose of haloperidol was administered twice over a 3-week interval in the presence or absence of a dietary tryptophan supplement added to the drinking water. Rats were assessed for disruption of locomotor behavior (using the rotorod) as well as the occurrence of spontaneous (dyskinetic-like) chewing and head twitching. It was observed that haloperidol impaired rotorod performance in a manner that paralleled the time course of the neurochemical changes in Experiment 1. In addition, the tryptophan (consumed at an average of 157 mg/kg/day) exacerbated the deficit in rotorod performance in haloperidol-treated rats after the first, but not after the second, haloperidol injection. Finally, the combination of haloperidol plus tryptophan was found to cause a long-lasting increase in spontaneous chewing movements that lasted 56 days after the first injection. These observations are interpreted in the context of tryptophan supplementation to antipsychotic therapy.