Neuropeptide Y-induced enhancement of the evoked release of newly synthesized dopamine in rat striatum:: Mediation byY2 receptors

The purpose of the present study was to determine whether or not activation of neuropeptide Y (NPY) receptors resulted in an enhancement or attenuation of the KCI (50 mM) evoked release of [H-3]dopamine newly synthesized from [H-3]tyrosine in superfused striatal slices and, if so to identify the NPY receptor subtype mediating the effect. Rat striatal slices were prepared and placed in microsuperfusion chambers and continuously superfused with physiological buffer containing 50 mu Ci/ml of L-3-5- [H-3]tyrosine. Superfusate effluents were collected and analyzed for [H-3]dopamine by liquid scintillation spectrometry following amberlite CG50 and alumina chromatography. NPY agonists (NPY and PYY3-36) were added 6 min prior to the addition of KCI, while the Y-1, Y-2, and Y-5 antagonist BIBO303304, BIIE0246 and CGP71683A, respectively were added 6 min prior to the agonists. Continuous superfusion with [H-3]tyrosine resulted in the production of [H-3]dopamine which reached a steady state at approximately 48 min. Depolarization with KCI resulted in a 2-to 3-fold increase in [H-3]dopamine overflow. NPY and PYY3-36 produced a concentration dependent enhancement in the KCl induced increase in newly synthesized [H-3]dopamine overflow. The Y-2 antagonist BIIE0246 produced an attenuation of both the NPY and PYY3-36 induced enhancement while the Y, antagonist BIB03304 and the Y-5 antagonist CGP71683A failed to alter the NPY or PYY3-36 induced enhancement. These results are consistent with the NPY-Y-2 receptor subtype mediating the facilitatory effect. (C) 2007 Elsevier Ltd. All rights reserved.