title: Metoclopramide potentiates d-amphetamine-induced hypermotility and stereotypy in rat.
abstract: The substituted benzamide metoclopramide has been reported to block the behavioral effects of dopamine agonists, whereas its congener sulpiride potentiates these effects. We injected metoclopramide 2.0, 4.0, or 8.0 mg/kg PO into rats 2 hr before d-amphetamine 1.5 mg/kg IP and measured locomotion for 3 hr. We injected metoclopramide 8.0 mg/kg PO into rats 2 hr before d-amphetamine 1.5, 3.0, or 6.0 mg/kg IP and measured stereotypy for 3 hr. Metoclopramide potentiated the effects of all doses of d-amphetamine on both measures; peak effects occurred in the second or third hr after d-amphetamine injection. Metoclopramide alone tended to reduce behavior. The results suggest that metoclopramide is qualitatively similar to sulpiride in its interaction with d-amphetamine, and that metoclopramide's mechanism of action is not a simple dopaminergic antagonism. Clinicians are advised that metoclopramide, which is presently extensively for gastrointestinal and other disorders, may interact adversely with drugs that affect dopaminergic function.
mesh_terms: D000818:Animals; D003913:Dextroamphetamine / Q000494:pharmacology*; D004357:Drug Synergism; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects*; D013997:Time Factors
chemical_list: D008787:Metoclopramide; D003913:Dextroamphetamine