Amphetamine-induced and spontaneous release of dopamine from A9 and A10 cell dendrites: an in vitro electrophysiological study in the mouse

Abstract

d-Amphetamine (d-AMP) is a potent releaser of dopamine (DA), and its central nervous system stimulant action is mediated primarily through its effect on the substantia nigra and ventral tegmental area dopaminergic neurons (nuclei A9 and A10, respectively). The purpose of the present experiment was to use electrophysiological techniques to examine dendritic release of DA in the in vitro slice preparation, and determine whether: (1) d-AMP inhibits the firing rates of both A9 and A10 cells; (2) the d-AMP-induced inhibition is mediated via the dendritic release of DA; and (3) there is spontaneous dendritic release of DA. Superfusion with d-AMP (2-100 microM) produced identical inhibitory dose-response curves for A9 and A10 cells, and a dose of 6.25 microM caused more than 50% inhibition in the cell firing rates. The d-AMP-induced inhibition was attenuated by blocking DA synthesis. Either D2 receptor blockade (sulpiride, 1 microM), or DA synthesis inhibition (alpha-methylparatyrosine, 50 microM) resulted in a marked increase in the firing rates of dopaminergic cells. These data suggest that d-AMP comparably releases DA from both A9 and A10 cell dendrites, that it releases newly-synthesized DA to inhibit cell firing, and that DA is tonically released to regulate cell firing rates via interactions with inhibitory D2 autoreceptors.