Amphetamine-induced release of dendritic dopamine in substantia nigra pars reticulata: D1-mediated behavioral and electrophysiological effects.

Abstract

Dopamine (DA) released from dendrites of substantia nigra dopaminergic neurons potentially is in a position to modulate basal ganglia outputs from the substantia nigra pars reticulata (SNR) via stimulation of D1 receptors on the terminals of striatonigral afferents. The effects of endogenous DA release in the SNR were examined in rats using behavioral activation, multiunit activity of SNR neurons, and cortical EEG pattern as dependent measures. Unilateral infusion of amphetamine (AMPH) into SNR (10 micrograms/0.5 microliter; 5 min) produced a short-lasting behavioral activation that was blocked by coinfusion of the D1 DA receptor antagonist SCH 23390 (0.5 micrograms). Multiunit recordings of SNR neurons in anesthetized rats showed that AMPH, infused as above, produced a rapid decrease in SNR activity. This decrease was maximal (approximately 90%) during the first 10 min postinfusion, followed by a gradual return to baseline levels. Coinfusion of SCH 23390 blocked the AMPH-induced decrease in SNR activity, although by itself this drug produced a 40% decrease in activity. Cortical EEG acquired during the SNR infusions/recordings showed a short-duration change in pattern immediately after AMPH infusion. A relative shift in power from the lowest frequency interval determined (0.8-2.7 Hz) to the next higher frequency interval (2.7-6.8 Hz) was observed which could be prevented by coinfusion of SCH 23390. Thus, dendritically released DA can inhibit the activity of SNR neurons via local stimulation of D1 receptors. This effect is associated with a brief behavioral activation and EEG desynchronization.