Title

Modulation of amphetamine-stimulated (transporter mediated) dopamine release in vitro by σ2 receptor agonists and antagonists

Document Type

Journal Article

Publication Date

4-10-1998

Journal

European Journal of Pharmacology

Volume

346

Issue

2-3

DOI

10.1016/S0014-2999(98)00063-6

Keywords

Caudate putamen; Cocaine; Dopamine transporter; Dopamine uptake

Abstract

Some σ receptor ligands have been shown to bind with low affinity to the dopamine transporter and to inhibit [3H]dopamine uptake. It has not previously been shown whether any of these compounds influence release of dopamine via facilitated exchange diffusion. To further examine the nature of the interaction between σ receptor ligands and the dopamine transporter, the effects of σ receptor ligands on amphetamine-stimulated [3H]dopamine release were examined in slices prepared from rat caudate putamen. In the absence of exogenous Ca2+, both (+)-pentazocine and (-)-pentazocine potentiated amphetamine-stimulated [3H]dopamine release at concentrations consistent with their affinities for σ2 receptors. In contrast, BD737 (1S,2R-(-)-cis-N-{2-(3,4-dichlorophenyl)ethyl}-N-methyl-2-(1- pyrrolidinyl)cyclohexylamine), a σ1 receptor agonist, had no effect on amphetamine-stimulated release. Neither isomer of pentazocine alone had any effect on basal [3H]dopamine release under these conditions. Three antagonists at σ receptors, one of which is non-selective for subtypes, and two of which are σ2-selective, all blocked the enhancement of stimulated release produced by (+)-pentazocine. Enhancement of stimulated release by (- )-pentazocine was similarly blocked by σ2 receptor antagonists. Our data support the contention that it is possible to regulate transporter-mediated events with drugs that act at a subpopulation of σ receptors pharmacologically identified as the σ2 subtype.

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