Neurosci Lett. 1990 Nov 13;119(2):159-62. Related Articles, Links


Non-competitive N-methyl-D-aspartate antagonists are potent activators of ventral tegmental A10 dopamine neurons.

French ED, Ceci A.

Department of Pharmacology, University of Arizona, College of Medicine, Tucson 85724.

The response of ventral tegmental (VTA) A10 dopamine neurons to a series of compounds covering the spectrum from high-affinity phencyclidine receptor ligands (MK-801, PCP) to high-affinity sigma-receptor ligands [+)-pentazocine, DTG) was measured using single-unit extracellular recording techniques in the rat. Dose-response comparisons revealed that MK-801 was 3, 6, 19 and 119 times more potent at activating A10 neurons than PCP, (+)-SKF-10,047, ketamine and (+)-pentazocine, respectively. DTG (1,3-di-o-tolylguanidine), the most selective sigma-ligand, and U50,488H, a kappa-opiate, failed to produce any stimulation of firing. Also, pretreatment with haloperidol, a potent sigma-receptor ligand, did not prevent MK-801-induced excitations. Thus, the activation of the A10-mesolimbic-mesocortical dopamine pathways by PCP, PCP-like drugs and sigma-psychotomimetics is mediated by the PCP receptor, not the haloperidol-sensitive sigma-receptor, with potencies directly correlated to their activity as non-competitive N-methyl-D-aspartate (NMDA) antagonists.