THE NMDA POSITIVE MODULATOR D-CYCLOSERINE INHIBITS DOPAMINE-MEDIATED BEHAVIORS IN THE RAT

The NMDA positive modulator D-cycloserine (DCS), which failed to modify rat spontaneous behavior, inhibited the hypermotility induced by the dopamine releaser methamphetamine as well as the behavioral responses to the selective stimulation of D-1 or D-2 dopamine receptors (SKF 38393 induced grooming and LY 171555 elicited hyperactivity, respectively). In contrast, behavioral responses to different doses of apomorphine (hypermotility and stereotypies) were not modified by the administration of DCS. No change in apomorphine-induced stereotyped behavior was observed during DCS repeated treatment (21 days), but an antagonism of dopaminergic stimulation occurred when DCS was repeatedly administered together with low doses of D-1 and D-2 dopamine receptor blockers [SCH 23390 and (-)-sulpiride]. Five days following the combined repeated treatment, behavioral dopaminergic supersensitivity was observed. The results are consistent with the view that an increase in glutamatergic function could decrease the response to dopaminergic stimulation.