Dopaminergic neurons in the rat ventral tegmental area. III. Effects of d-and l-amphetamine

Abstract

The effect of d- and l-isomers of amphetamine on the activity of mesolimbic and mesocortical dopamine (DA) neurons in the ventral tegmental area (VTA or A10) was studied in chloral hydrate anesthetized rats. Mesolimbic and mesocortical DA neurons were identified by their antidromic responses to stimulation of the nucleus accumbens (NAc) and the frontal-cingulate cortices, respectively. Similar to their effects on A9 DA cells, d-A was found to be 9.2-fold more potent than l-A in producing 50% inhibition of discharge rate of A10 DA neurons. In addition, pre-treatment with αMT caused approximately a 5-fold increase in the ID 50 of d-A. The depressant effect of d-A could be completely prevented by pre-treatment with both reserpine and αMT; the blockade of d-A effect by reserpine and αMT could be reversed by injections of low doses of l-DOPA. However, unlike its effect on A9 DA cells, the depressant action of d-A on A10 DA neurons was not mediated by forebrain feedback pathways; in rats with either destruction of neuronal perikarya in the NAc by ibotenic acid or acute dience-phalic transection, the IDso of d-A on A10 DA cells remained unchanged. It is concluded that 1. (1) d-A is much more potent than l-A in depressing firing activity of identified A10 DA neurons, and 2. (2) the depressant effect of amphetamine on A10 DA cells is not mediated via a forebrain feedback loop; it may be mediated by a DA dendro-dendritic and/or axon collateral autoregulatory system.