EFFECTS OF SIGMA-RECEPTOR LIGANDS ON THE EXTRACELLULAR CONCENTRATION OF DOPAMINE IN THE STRIATUM AND PREFRONTAL CORTEX OF THE RAT

The extracellular concentration of dopamine in the striatum and medial prefrontal cortex of the rat was determined following the systemic ad ministration of sigma receptor ligands. The (+)-benzomorphan, (+)-pent azocine, significantly increased the extracellular concentration of do pamine in the striatum and medial prefrontal cortex. A stimulatory eff ect on the extracellular concentration of dopamine in the striatum als o was produced by the (+)-, but not the (-)-, enantiomer of N-allylnor metazocine, as well as by the non-benzomorphans 1-(cyclopropylmethyl)- 4-(2'-(4 ''-fluorophenl)-2'-oxoethyl)-piperidine (DUP 734) and (-)-but aclamol. In contrast, the dopamine concentration was unaffected by di- o-tolylguanidine and markedly suppressed by (+)-3-[3-hydroxyphenyl]-N- (1-propyl)piperidine (3-PPP). Finally, the (+)-pentazocine-induced ele vation of the extracellular concentration of dopamine was not suppress ed by an inhibitor of the dopamine transporter, phenyl)methoxy]ethyl]- 4-[3-phenylpropyl]piperazine (GBR 12909). Thus, benzomorphan, e.g., ()-pentazocine and(+)-N-allylnormetazocine, and non-benzomorphan, e.g., DUP 734 and (-)-butaclamol, a receptor ligands appear to facilitate d opamine release from nigrostriatal, and presumably mesocorticolimbic, neurons through a non-transporter-mediated mechanism.