Biphasic effect of sigma receptor ligands on the extracellular concentration of dopamine in the striatum of the rat

Summary.

The extracellular concentration of dopamine in the striatum of the rat was determined following the intrastriatal infusion of sigma ligands. The administration of (+)-pentazocine (0.3 and 1.0 mM) through a microdialysis probe for 120 min resulted in a biphasic effect on the extracellular concentration of dopamine: a brief increase of approximately 70% followed by a prolonged decrease of approximately 65%. A similar effect on dopamine release was elicited by the (−)-isomer of pentazocine, as well as by di-o-tolylguanidine. In addition, the infusion of the NMDA antagonist 3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (CPP) (100 μM) through the dialysis probe significantly attenuated the initial increase but not the subsequent decrease in dopamine release produced by the intrastriatal infusion of (+)-pentazocine. These data are suggestive that dopamine release in the striatum may be modulated by multiple sigma receptor subtypes and that NMDA receptors may mediate the stimulatory effect of sigma ligands on dopamine release in the striatum.