Abstract
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 also was produced by the (+)-, but not the (-)-, enantiomer of N-allylnormetazocine, as well as by the non-benzomorphans 1-(cyclopropylmethyl)-4-(2'-(4"-fluorophenyl)-2'-oxoothyl-piper idi ne (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, sigma receptor ligands appear to facilitate dopamine release from nigrostriatal, and presumably mesocorticolimbic, neurons through a non-transporter-mediated mechanism.
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