Dose-dependent biphasic alterations in the spontaneous activity of neurons in the rat neostriatum produced by d-amphetamine and methylphenidate.

A dose-response analysis was performed on D-amphetamine- and methylphenidate-induced changes in neuronal activity in the neostriatum of immobilized, phenidate-induced changes in neuronal activity in the neostriatum of immobilized, locally anesthetized rats. Whereas a marked depression of firing rate characterized the response to intraperitoneal injections of 2.5 mg/kg D-amphetamine or 10 mg/kg methylphenidate, increasing the dose (5.0--7.5 mg/kg D-amphetamine and 20--25 mg/kg methylphenidate) shifted this response pattern to a prolonged increase in activity. Both stimulant-induced increases and decreases in neostriatal activity are reversed by 2.0 mg/kg haloperidol. In contrast to the response of neostriatal neurons, the firing rate in the substantia nigra pars compacta was inhibited by both stimulants, even at doses that increased the activity of neurons in the neostriatum. The possible mechanisms underlying these drug-induced changes in firing rate are discussed along with the behavioral implications of a stimulant-induced dose-dependent shift in neostriatal unit activity.