MK-801 induced stereotypies in rats are decreased by haloperidol and increased by diazepam

The effects of haloperidol and diazepam were investigated on stereotypies (wall contacts and turn rounds) induced by the non-competitive NMDA antagonist MK-801 in rats. Haloperidol (0.03, 0.10, 0.25 and 0.40 mg/kg body weight) caused a dose-dependent antagonism whereas diazepam (3.0 and 5.0 mg/kg) caused a dose-dependent agonism of the stereotypies induced by 0.30 mg/kg MK-801 (all drugs given intraperitoneal). Conversely, diazepam (5.0 mg/kg) given alone reduced significantly the number of spontaneous wall contacts and turn rounds. The paradoxial stimulation of MK-801 induced stereotypies by diazepam could be explained by a shift between positive and negative corticostriatothalamic feedback loops envolving GABAergic neurons in favour of the former.