Frustrative nonreward: Chemogenetic inactivation of the central amygdala abolishes the effect of reward downshift without affecting alcohol intake.

The role of the central amygdala (CeA) in the adjustment to a 32-to-2% sucrose downshift in the consummatory successive negative contrast (cSNC) task and in a free-choice 10% alcohol-water preference task (PT) was studied using chemogenetic inactivation. cSNC is a model of frustrative nonreward that enhances alcohol consumption. In Experiment 1, sessions 1-10 involved 5-min access to 32% sucrose and sessions 11-12 involved access to 2% sucrose. Vehicle or clozapine N-oxide (CNO; 1 or 3 mg/kg, ip), used later to activate the inhibitory designer receptor, was administered 30 min before sessions 11-12. There was no evidence that CNO affected consummatory behavior after the sucrose downshift. In Experiment 2, all animals received an infusion of the inhibitory designer receptor hM4D(Gi) into the CeA. After recovery, animals received access to either 32% or 2% sucrose on sessions 1-10, followed by 2% sucrose on sessions 11-12. Immediately after each 5-min sucrose session, animals received a 2-bottle, 1-h PT with 10% alcohol and water. CNO (3 mg/kg, ip) or vehicle was administered 30 min before sessions 11-12. CeA inactivation prior to sucrose downshift eliminated the cSNC effect, which was observed in vehicle controls. However, there was no evidence that CeA inactivation affected preference for 10% alcohol over water. These results support the hypothesis that CeA activity is critical for cSNC effect, an outcome consistent with the view that the amygdala plays a central role in frustrative nonreward.