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OtherNEUROPHARMACOLOGY

Modulation of [3H]Dopamine Release from Rat Nucleus Accumbens by Neuropeptide Y May Involve a Sigma 1-like Receptor

David T. Ault, Julie M. Radeff and Linda L. Werling
Journal of Pharmacology and Experimental Therapeutics February 1998, 284 (2) 553-560;
David T. Ault
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Julie M. Radeff
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Linda L. Werling
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Abstract

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.

Footnotes

  • Send reprint requests to: Linda L. Werling, Department of Pharmacology, The George Washington University Medical Center, 2300 I Street, N.W., Washington, DC 20037.

  • ↵1 This work was supported by a grant from NIDA to Linda L. Werling and a predoctoral fellowship from NIDA to David T. Ault.

  • Abbreviations:
    ANOVA
    analysis of variance
    BD737
    1S,2R-(-)-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)-cyclohexylamine
    BD1008
    N-[2-(3,4-dichlorophenyl)-ethyl]-N-methyl-2-pyrrolidinyl)ethylamine
    BIMU-8
    (endo-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3-dihydro-(1-methyl)ethyl-2-oxo-1H-benzimidazole-1-carboxyamidehydrochloride
    DA
    dopamine
    DuP734
    1-(cyclopropylmethyl)-4-2′-4"-fluorophenyl)-2′-oxoethyl)piperidine HBr
    MKB
    modified Krebs-HEPES buffer
    NMDA
    N-methyl-d-aspartate
    NPY
    Neuropeptide Y
    PYX-1
    Ac-[3-(2,6-dichlorobenzyl)Tyr27,d-Thr32]NPY-(27-36) amide
    PYY
    peptide YY
    • Received June 19, 1997.
    • Accepted October 20, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 284, Issue 2
1 Feb 1998
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OtherNEUROPHARMACOLOGY

Modulation of [3H]Dopamine Release from Rat Nucleus Accumbens by Neuropeptide Y May Involve a Sigma 1-like Receptor

David T. Ault, Julie M. Radeff and Linda L. Werling
Journal of Pharmacology and Experimental Therapeutics February 1, 1998, 284 (2) 553-560;

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OtherNEUROPHARMACOLOGY

Modulation of [3H]Dopamine Release from Rat Nucleus Accumbens by Neuropeptide Y May Involve a Sigma 1-like Receptor

David T. Ault, Julie M. Radeff and Linda L. Werling
Journal of Pharmacology and Experimental Therapeutics February 1, 1998, 284 (2) 553-560;
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