Modulation of [H-3]dopamine release by neuropeptide Y in rat striatal slices

Neuropeptide Y, a 36-amino-acid peptide, has a wide and specific distribution in the central nervous system. In this study we examined the regulatory mechanisms of neuropeptide Y on dopamine release in the rat central nervous system. The effects of neuropeptide Y on the electrically stimulated [H-3]dopamine release were investigated in superfused striatal slices of Sprague-Dawley rats, spontaneously hypertensive rats and Wistar-Kyoto rats, Neuropeptide Y (1x10(-8)-1x10(-7) mol/l) reduced the stimulation (1 Hz)-induced [H-3]dopamine release by a comparable amount in Sprague-Dawley rats, The blockade of dopamine D-2 receptors by the dopamine D-2 receptor antagonist, sulpiride, diminished the inhibitory effects of neuropeptide Y on the stimulation-evoked [H-3]dopamine release. Pretreatment of slices with pertussis toxin (a potent inhibitor of G(i)-proteins) attenuated the suppression of the stimulation-evoked [H-3]dopamine release by neuropeptide Y. Unlabelled dopamine itself reduced the stimulation-evoked [H-3]dopamine release, and the inhibitory effect was also attenuated in the pertussis toxin-pretreated slices. In spontaneously hypertensive rats, the inhibitory effect of neuropeptide Y on the stimulation-evoked [H-3]dopamine release was more pronounced than that in Wistar-Kyoto rats. The results of the present study showed that neuropeptide Y inhibited the stimulation-evoked dopamine release partially mediated by dopamine D-2 receptors and the pertussis toxin-sensitive G(i)-proteins in rat striatum. Furthermore, the greater effect of neuropeptide Y on dopamine release in spontaneously hypertensive rats suggests a possible involvement of the peptide in regulating the central dopaminergic nerve activity in hypertension.