Blockade of central nicotine acetylcholine receptor signaling attenuate ghrelin-induced food intake in rodents

S. L. Dickson, E. Hrabovszky, C. Hansson, E. Jerlhag, M. Alvarez-Crespo, K. P. Skibicka, C. S. Molnar, Z. Liposits, J. A. Engel, E. Egecioglu

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60 Scopus citations

Abstract

Here we sought to determine whether ghrelin's central effects on food intake can be interrupted by nicotine acetylcholine receptor (nAChR) blockade. Ghrelin regulates mesolimbic dopamine neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens, partly via cholinergic VTA afferents originating in the laterodorsal tegmental area (LDTg). Given that these cholinergic projections to the VTA have been implicated in natural as well as drug-induced reinforcement, we sought to investigate the role of cholinergic signaling in ghrelin-induced food intake as well as fasting-induced food intake, for which endogenous ghrelin has been implicated. We found that i.p. treatment with the non-selective centrally active nAChR antagonist, mecamylamine decreased fasting-induced food intake in both mice and rats. Moreover, central administration of mecamylamine decreased fasting-induced food intake in rats. I.c.v. ghrelin-induced food intake was suppressed by mecamylamine i.p. but not by hexamethonium i.p., a peripheral nAChR antagonist. Furthermore, mecamylamine i.p. blocked food intake following ghrelin injection into the VTA. Expression of the ghrelin receptor, the growth hormone secretagogue receptor 1A, was found to co-localize with choline acetyltransferase, a marker of cholinergic neurons, in the LDTg. Finally, mecamylamine treatment i.p. decreased the ability of palatable food to condition a place preference. These data suggest that ghrelin-induced food intake is partly mediated via nAChRs and that nicotinic blockade decreases the rewarding properties of food.

Original languageEnglish (US)
Pages (from-to)1180-1186
Number of pages7
JournalNeuroscience
Volume171
Issue number4
DOIs
StatePublished - Dec 29 2010

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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