Neuropeptide Y (NPY)-induced suppression of activity in the rat: evidence for NPY receptor heterogeneity and for interaction with α-adrenoceptors

Markus Heilig, Claes Wahlestedt, Erik Widerlöv

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90 Scopus citations


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 α-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 α2-adrenoceptor antagonist, idazoxan (0.125 mg/kg intraperitoneally, i.p.), was even more effective, while the selective α1-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 α2-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.

Original languageEnglish (US)
Pages (from-to)205-213
Number of pages9
JournalEuropean Journal of Pharmacology
Issue number2-3
StatePublished - Nov 22 1988
Externally publishedYes


  • (Interactions, Behaviour)
  • Adrenoceptors
  • Neuropeptide Y
  • Sedation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology


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