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 s everal electrophysiological assays to determine whether it exhibits pr eferential effects in the mesolimbic versus nigrostriatal dopamine sys tems. Extracellular single unit activities of substantia nigra pars co mpacta (A9) and ventral tegmental area (A10) dopamine neurons, and cau date-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 neuro ns (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 t han 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 d ifferences in potency for either form in inhibiting A9 and A10 dopamin e neurons. In other studies, iontophoretically applied (+)-7-OH-DPAT c aused current-dependent inhibitions of spontaneously active or glutama te-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 rec ordings from freshly dissociated rat caudate-putamen neurons, an 85 pS K+ channel known to be activated by dopamine and the ''D-2-like'' ago nist quinpirole was also observed with (+)-7-OH-DPAT (0.2-1 mu M) appl ied in the patch pipette. Although dopamine D-3 receptors have been th ought to play an important role in limbic areas, these results suggest that 7-OH-DPAT behaves similarly to dopamine D-2 agonists and does no t discriminate between nigrostriatal and mesolimbic systems.