Alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors are involved in mediating the ghrelin-induced locomotor stimulation and dopamine overflow in nucleus accumbens

Abstract

Previously, we have reported that the orexigenic peptide ghrelin activates the cholinergic–dopaminergic reward link, involving nicotinic acetylcholine receptors (nAChR). The α 3-α 7 and β 2-β 4 subunits of the nAChR can be combined into pentameric nAChRs, with different functional roles. The present experiments show that the locomotor stimulatory effects of ghrelin, either into laterodorsal tegmental area (LDTg) or ventral tegmental area (VTA), are mediated via ventral tegmental nAChR, but neither the α 4β 2⁎ (using dihydro-β-erythroidine) nor the α 7⁎ (using methyllycaconitine) subtypes appears to be involved. On the other hand, the α 3β 2⁎, β 3⁎ and/or α 6⁎ (using α-conotoxin MII) subtypes in the VTA mediate the stimulatory and DA-enhancing effects of ghrelin, a pattern that ghrelin shares with ethanol ( n = 5–8). Radioligand-binding experiments shown that ghrelin does not interfere directly with nAChRs ( n = 26). We therefore suggest that the α 3β 2⁎, β 3⁎ and/or α 6⁎ subtypes might be pharmacological targets for treatment of addictive behaviours including compulsive overeating and alcoholism.