Suppression of ethanol self-administration by the neuropeptide Y (NPY) Y2 receptor antagonist BIIE0246: evidence for sensitization in rats with a history of dependence
2005 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 375, no 2, 129-133 p.Article in journal (Refereed) Published
Evidence from genetically modified mice suggests a role for NPY in regulation of ethanol intake, but results of pharmacological studies have been more variable. We have previously shown that potentiation of NPY signaling through antagonism at NPY-Y2 receptors decreases operant responding for ethanol in Wistar rats without a history of dependence. Here, we examined the effects of Y2-antagonism in animals with a history of dependence induced by long-term intermittent exposure to ethanol vapor. The Y2-receptor antagonist BIIE0246 suppressed operant responding for ethanol (approximately 50%, p=0.01), at a dose (0.5 nmol i.c.v.) which was ineffective in subjects without a history of dependence. Responding for the ethanol-free control solution was unaffected. These data confirm that antagonism at central NPY-Y2 receptors selectively suppresses motivation to self-administer ethanol, and indicate that the NPY system is sensitized in animals with a history of dependence. This may render the NPY system, and Y2 receptors in particular, an attractive target for treatment of alcohol dependence.
Place, publisher, year, edition, pages
Elsevier, 2005. Vol. 375, no 2, 129-133 p.
IdentifiersURN: urn:nbn:se:liu:diva-101865DOI: 10.1016/j.neulet.2004.10.084PubMedID: 15670655OAI: oai:DiVA.org:liu-101865DiVA: diva2:666707