Behavioural, pharmacological and biochemical effects of acute and chronic administration of ketamine in the rat.

ABSTRACT

The effects of N-methyl-D-aspartate (NMDA) antagonist ketamine given acutely or chronically were investigated on dopamine-related motor functions. Acute administration (15, 22.5, 30 mg/kg, i.p.) reversed the catalepsy induced by a dopamine (DA) antagonist (haloperidol, 0.25 mg/kg, i.p.) in the rat. When given orally and chronically (15 mg/kg per day) during at least 60 days, no alteration of spontaneous motor behaviour was observed, but the responsiveness to a DA agonist (apomorphine, 0.125 or 0.25 mg/kg s.c.) and to haloperidol was enhanced, suggesting an hypersensitivity of the DA receptors following the chronic blockade of NMDA receptors. However, following prolonged administration of ketamine there were no alteration of DA levels and turnover. Taken together these results suggest that the mechanisms involved in this DA receptor hypersensitivity should be postsynaptic.