Melanocortins have been reported to affect alcohol intake through actions in the hypothalamus thought to be mediated by melanocortin MC4 receptors. Since these receptors are expressed in a number of amygdala regions, we have explored their role in the regulation of alcohol intake in both alcohol-preferring (P) and non-preferring (NP) rats. Injections were made at the border of the central amygdala nucleus and the basolateral amygdala. The MC3/MC4R agonist MTII reduced alcohol and food intake but increased water intake while the selective MC4R antagonist HS014 only increased food and water intake. The MC3/MC4R antagonist SHU9119 increased food and water but had little effect on alcohol intake. However, when the SHU9119 stimulation of food intake was prevented by pair-feeding, SHU9119 induced a large and prolonged decline in alcohol intake that was paralleled by an increase in water intake. These effects were only observed in P rats. We conclude that melanocortin activity in the amygdala can alter the selective preference for water and alcohol independent of effects on food intake.
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