Opposite effects of sulpiride and metoclopramide on amphetamine-induced stereotypy

The effects of the atypical neuroleptic sulpiride (0-20 mg/kg s.c.) and the classical neuroleptic metoclopramide (0-4 mg/kg s.c.) on behaviours produced by D-amphetamine (0-5 mg/kg i.p.) were measured in a time-sampling observational paradigm in rats. Sulpiride had one clear dose-dependent effect: it enhanced amphetamine-induced stereotyped behaviours (repetitive head movements, sniffing down and some gnawing). In contrast, metoclopramide dose-dependently decreased amphetamine-induced stereotypy, locomotion, rearing, and sniffing up, and concurrently antagonized the suppression of lying down produced by amphetamine. Sulpiride's facilitatory effects on amphetamine-induced stereotypy follow a pattern previously observed for two other atypical neuroleptics: clozapine and thioridazine. This may be a common effect of atypical neuroleptics. Since these neuroleptics are antipsychotic, amphetamine-induced stereotypy appears to be a poor animal model for human psychoses. It is suggested that sulpiride's effects may be mediated through a preferential presynaptic versus postsynaptic action on dopamine neurons in the nigrostriatal bundle.