PT  - JOURNAL ARTICLE
AU  - David T. Ault
AU  - Julie M. Radeff
AU  - Linda L. Werling
TI  - Modulation of [<sup>3</sup>H]Dopamine Release from Rat Nucleus Accumbens by Neuropeptide Y May Involve a <em>Sigma</em>
<sub>1</sub>-like Receptor
DP  - 1998 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 553--560
VI  - 284
IP  - 2
4099  - http://jpet.aspetjournals.org/content/284/2/553.short
4100  - http://jpet.aspetjournals.org/content/284/2/553.full
SO  - J Pharmacol Exp Ther1998 Feb 01; 284
AB  - Sigma receptors are located in limbic areas, including the nucleus accumbens, where increased dopamine levels have been linked to psychosis and reinforcement. Neuropeptide Y (NPY) has been named as a possible endogenous ligand for a subpopulation of ς receptors on the basis of its ability to compete for ς receptor binding. Using a superfusion system, we found that NPY enhanced N-methyl-d-asparate-stimulated [3H]dopamine release in rat nucleus accumbens, whereas the prototypical ς agonist (+)pentazocine inhibited release. However, four ς antagonists, one of which is ς1 selective, as well as a Y receptor antagonist, all reversed the enhancement by NPY and the inhibition by (+)pentazocine. A ς2-selective antagonist had no effect on either NPY-mediated enhancement or (+)pentazocine-mediated inhibition. [Leu31,Pro34]NPY and NPY13–36also enhanced release, but the effects were not reversed by ς antagonists. Peptide YY did not mimic the effect of NPY. Our findings are consistent with the potential role of NPY as an endogenous ligand for a subtype of ς receptor with characteristics different from Y1, Y2 and Y3 receptors but sensitive to Ac-[3-(2,6-dichlorobenzyl)Tyr27,d-Thr32NPY-(27–36)amide. Our findings suggest a role for NPY, via ς receptors, in the regulation of dopamine levels in areas of brain critical to psychosis and reinforcement. The American Society for Pharmacology and Experimental Therapeutics