sigma(1) Receptors in rat striatum regulate NMDA-stimulated [H-3]dopamine release via a presynaptic mechanism

The role of the sigma(1) receptor in the regulation of N-methyl-D-aspartate (NMDA)-stimulated [H-3]dopamine release from rat striatal slices was examined. The sigma receptor agonist 1S,2R-(-)-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine (BD737) inhibited stimulated release in a concentration-dependent manner. The sigma(1) receptor antagonist, 1-(cyclopropylmethyl)-4-(2'-(4 ''-fluorophenyl)-2'-oxoethyl)piperidine Hbr (DuP 734), reversed inhibition of release by BD737. Haloperidol, di-o-tolylguanidine (DTG) and N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (BD1008) reversed the BD737-mediated inhibition of release. Haloperidol and DTG also antagonized inhibition of stimulated release by (+)-pentazocine. Furthermore, BD737 and (+)-pentazocine inhibited stimulated release in the presence of tetrodotoxin, suggesting that sigma(1) receptors regulating dopamine release are located on dopaminergic nerve terminals. These data suggest that sigma(1) receptors may be important in the regulation of glutamate-stimulated dopamine release.