Shift from inhibition to excitation in the neostriatum but not in the nucleus accumbens following long-term amphetamine.

Neuronal responses to 1.0 or 5.0 mg/kg D-amphetamine were recorded simultaneously in the neostriatum and nucleus accumbens of rats pretreated twice daily with these doses or with saline for 6 consecutive days. In all groups, the number of neurons responding to a challenge injection of either dose of amphetamine with an overall excitation or inhibition was not significantly different. During the first 30-60 min of the drug response, however, neurons in the neostriatum of amphetamine-pretreated rats responded with a significant increase in firing rate compared to saline controls. In the nucleus accumbens, on the other hand, tolerance developed to the inhibition produced by 1.0 mg/kg D-amphetamine, whereas the responses produced by 5.0 mg/kg were not significantly altered by long-term treatment. Liquid chromatography with electrochemical detection revealed that pretreatment with 5.0 mg/kg D-amphetamine produced a slight, but significant, reduction of dopamine and norepinephrine levels in the neostriatum. Catecholamine levels were not significantly altered in the nucleus accumbens by either dose. These electrophysiological and neurochemical changes are discussed in relation to the known involvement of these sites in the dose-dependent behavioral alterations that accompany repeated amphetamine injections.