Archival ReportSigma Receptor Agonists: Receptor Binding and Effects on Mesolimbic Dopamine Neurotransmission Assessed by Microdialysis
Section snippets
σ1 and σ2 Receptor Binding
Frozen whole guinea pig brains (minus cerebellum) were used and processed as already published (37) (see also Supplement 1 for complete details). The guinea pig brains were preferred over rat brains due to their use as a standard for σ-receptor binding because of the relatively higher density of those receptors in that tissue compared with the rat (38). Ligand binding experiments were conducted for σ1-receptor studies with 3 nmol/L [3H](+)-pentazocine (specific activity 28 Ci/mmol) and 8.0 mg
In Vitro Binding Experiments
As has been previously reported (47, 48), DTG and PRE-084 had high affinity for σ-receptors. The homologous competition of DTG modeled better for two than one binding site (Table 1). The high affinity binding Kd value of 21.9 nmol/L is comparable with that reported previously for σ2-receptors in the papers cited above and indicates a twofold to threefold selectivity for σ2 over σ1-receptors, as also reported previously. In contrast, PRE-084 had a high affinity for σ1-receptors (53.2 nmol/L) and
Discussion
A recent study with rodents on self-administration of the σ-receptor agonists DTG and PRE-084 (26) prompted the present study of the effects of these drugs on DA levels in the NAc shell. The goal of the present study was to assess whether the effectiveness of DTG and PRE-084 in maintaining self-administration behavior would correspond with an increase in DA neurotransmission in the NAc shell after acute administration. This correspondence has been found with most drugs abused by humans (28, 29,
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