Title

Neuropeptide Y-mediated enhancement of NMDA-stimulated [3H]dopamine release from rat prefrontal cortex is reversed by σ1 receptor antagonists

Document Type

Journal Article

Publication Date

5-4-1998

Journal

Schizophrenia Research

Volume

31

Issue

1

DOI

10.1016/S0920-9964(98)00002-4

Keywords

σ Receptors; Dopamine release; Neuropeptide Y; Prefrontal cortex; PYX-I

Abstract

Sigma (σ) receptors are located in limbic areas, including the prefrontal cortex, where decreased dopamine levels have been linked to negative symptoms. Although the endogenous ligands for σ receptors are unknown, neuropeptide Y (NPY) has been named as the potential endogenous agonist at these receptors. NPY enhanced NMDA-stimulated [3H]dopamine release in rat prefrontal cortex. This was in contrast to the inhibition produced by the σ agonists (+)pentazocine and BD737. However, four σ antagonists, including one which is σ1 selective, that reverse (+)pentazocine- or BD737-mediated inhibition all reversed the NPY-mediated enhancement. In addition, PYX-1, a Y receptor antagonist, reversed both the (+)pentazocine- and BD737-mediated inhibition and the NPY-mediated enhancement of release. Peptide YY (PYY). [Leu34,Pro34]Npy and NPY13-36, did not mimic the effect of NPY. Our findings are consistent with NPY acting as an endogenous ligand for a subtype of a receptor with characteristics different from Y1, Y2 and Y3 receptors but sensitive to PYX-I. These findings suggest a role for NPY, via σ receptors, as a modulator of dopamine levels in the prefrontal cortex.

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