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 administration of sigma receptor ligands. The (+)-benzomorphan, (+)-pentazocine, significantly increased the extracellular concentration of dopamine in the striatum and medial prefrontal cortex. A stimulatory effect on the extracellular concentration of dopamine in the striatum also was produced by the (+)-, but not the (-)-, enantiomer of N-allylnormetazocine, as well as by the non-benzomorphans 1-(cyclopropylmethyl)-4-(2'-(4 ''-fluorophenl)-2'-oxoethyl)-piperidine (DUP 734) and (-)-butaclamol. 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 elevation of the extracellular concentration of dopamine was not suppressed by an inhibitor of the dopamine transporter, 1-[2-[bis(4-fluorophenyl)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 dopamine release from nigrostriatal, and presumably mesocorticolimbic, neurons through a non-transporter-mediated mechanism.