Neuropeptide Y (NPY)-induced suppression of activity in the rat: evidence for NPY receptor heterogeneity and for interaction with alpha-adrenoceptors.
The receptor mechanisms mediating the neuropeptide Y (NPY)-induced suppression of behavioural activity have been examined in the rat. The interaction of NPY with central noradrenergic mechanisms was also studied. The non-selective alpha-adrenoceptor antagonist, phentolamine (15-60 nmol intracerebroventricularly, i.c.v.), caused a dose-related antagonism (up to 50%) of the NPY-induced suppression of activity. The selective alpha 2-adrenoceptor antagonist, idazoxan (0.125 mg/kg intraperitoneally, i.p.), was even more effective, while the selective alpha 1-adrenoceptor antagonist, prazosin, was without effect. In addition, we examined whether the recently postulated subdivision of peripheral NPY receptors was also applicable to the brain. The ability of the C-terminal 13-36 amino acid fragment of NPY (postulated to activate NPY-Y2 receptors) to reproduce the effects of the full molecule (postulated to activate both NPY-Y1 and -Y2 receptors) was tested. NPY-(13-36) (0.4-10.0 nmol i.c.v.) failed to produce any suppression of activity. On the contrary, it produced an increase in locomotor activity and rearings at low doses. This effect was not blocked by phentolamine. We conclude that the NPY-induced suppression of activity is produced to a large extent by modulation of alpha 2-adrenergic transmission. Our results also provide evidence for heterogeneity among the central NPY receptors, with the NPY-induced suppression of activity being mediated by the NPY-Y1 receptor subtype.
Heilig
M
M
Department of Psychiatry and Neurochemistry, University of Lund, Sweden.
Wahlestedt
C
C
Widerlöv
E
E
D000818:Animals; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009478:Neuropeptide Y / Q000494:pharmacology*; D010646:Phentolamine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D009478:Neuropeptide Y; D011942:Receptors, Adrenergic, alpha; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter; D010646:Phentolamine