Dopamine release in human neocortical slices: Characterization of inhibitory autoreceptors and of nicotinic acetylcholine receptor-evoked release

Abstract

The autoinhibitory control of electrically evoked release of [ 3H]-dopamine and the properties of that induced by nicotinic receptor (nAChR) stimulation were studied in slices of the human neocortex. In both models [ 3H]-dopamine release was action potential-induced and exocytotic. The selective dopamine D 2 receptor agonist (−)-quinpirole reduced electrically evoked release of [ 3H]-dopamine, yielding IC 50 and I max values of 23 nM and 76%, respectively. Also, the effects of several other subtype-selective dopamine receptor ligands confirmed that the terminal dopamine autoreceptor belongs to the D 2 subtype. The autoinhibitory feedback control was slightly operative under stimulation conditions of 90 pulses and 3 Hz, with a biophase concentration of endogenous dopamine of 3.6 nM, and was enhanced under blockade of dopamine reuptake. [ 3H]-dopamine release evoked in an identical manner in mouse neocortical slices was not inhibited by (−)-quinpirole, suggesting the absence of dopamine autoreceptors in this tissue and underlining an important species difference. Also, nAChR stimulation-induced release of [ 3H]-dopamine revealed a species difference: [ 3H]-dopamine release was evoked in human, but not in rat neocortical slices. The nAChRs inducing [ 3H]-dopamine release most probably belong to the α 3/β 2-subtype, according to the potencies and efficacies of subtype-selective nAChR ligands. Part of these receptors may be located on glutamatergic neurons.