THE PUTATIVE DOPAMINE D-3 RECEPTOR AGONIST 7-OH-DPAT - LACK OF MESOLIMBIC SELECTIVITY

7-Hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT), an agonist with relative selectivity for the dopamine D-3 receptor, was examined in several electrophysiological assays to determine whether it exhibits preferential effects in the mesolimbic versus nigrostriatal dopamine systems. Extracellular single unit activities of substantia nigra pars compacta (A9) and ventral tegmental area (A10) dopamine neurons, and caudate-putamen and nucleus accumbens neurons, were recorded in male rats anesthetized with chloral hydrate. Intravenous (i)-7-OH-DPAT potently and completely inhibited the firing of both A9 and A10 dopamine neurons (ED(50)'s: 3.5 +/- 0.7 mu g/kg and 3.9 +/- 9 mu g/kg, respectively). The active enantiomer, (+)-7-OH-DPAT, was 2 to 3 times more potent than the racemic drug (ED(50)'s: 1.2 +/- 0.3 mu g/kg and 1.7 +/- 0.4 mu g/kg for A9 and A10 cells, respectively). There were no significant differences in potency for either form in inhibiting A9 and A10 dopamine neurons. In other studies, iontophoretically applied (+)-7-OH-DPAT caused current-dependent inhibitions of spontaneously active or glutamate-driven caudate-putamen and nucleus accumbens neurons (I-50 values, 6.5 and 7.9 nA, respectively). Again, no difference in potency between cell populations was noted. Finally, in cell-attached patch-clamp recordings from freshly dissociated rat caudate-putamen neurons, an 85 pS K+ channel known to be activated by dopamine and the ''D-2-like'' agonist quinpirole was also observed with (+)-7-OH-DPAT (0.2-1 mu M) applied in the patch pipette. Although dopamine D-3 receptors have been thought to play an important role in limbic areas, these results suggest that 7-OH-DPAT behaves similarly to dopamine D-2 agonists and does not discriminate between nigrostriatal and mesolimbic systems.