Palatable food access impacts expression of amylin receptor components in the mesocorticolimbic system.

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findingsWhat is the central question of this study? We tested whether intra-nucleus accumbens core amylin receptor (AmyR) activation suppresses feeding and evaluated whether intake of palatable food influences mesocorticolimbic AmyR expression. What is the main finding and its importance? Intra-nucleus accumbens core AmyR activation reduces food intake in some dietary conditions. We showed that all components of the AmyR are expressed in the prefrontal cortex and central nucleus of the amygdala and demonstrated that access to fat impacts AmyR expression in these and other mesocorticolimbic nuclei. These results suggest that the intake of palatable food might alter amylin signalling in the brain and shed further light onto potential sites of action for amylin. ABSTRACT: Amylin is a pancreas- and brain-derived peptide that acts within the CNS to promote negative energy balance. However, our understanding of the CNS sites of action for amylin remains incomplete. Here, we investigate the effect of amylin receptor (AmyR) activation in the nucleus accumbens core (NAcC) on the intake of bland and palatable foods. Intra-NAcC injection of the AmyR agonist salmon calcitonin or amylin itself in male chow-fed rats had no effect on food intake, meal size or number of meals. However, in chow-fed rats with access to fat solution, although fat intake was not affected by intra-NAcC AmyR activation, subsequent chow intake was suppressed. Given that mesolimbic AmyR activation suppresses energy intake in rats with access to fat solution, we tested whether fat access changes AmyR expression in key mesocorticolimbic nuclei. Fat exposure did not affect NAcC AmyR expression, whereas in the accumbens shell, expression of receptor activity modifying protein (RAMP) 3 was significantly reduced in fat-consuming rats. We show that all components of AmyRs are expressed in the medial prefrontal cortex and central nucleus of the amygdala; fat access significantly reduced expression of calcitonin receptor-A in the central nucleus of the amygdala and RAMP2 in the medial prefrontal cortex. Taken together, these results indicate that intra-NAcC AmyR activation can suppress energy intake and, furthermore, suggest that AmyR signalling in a broader range of mesocorticolimbic sites might have a role in mediating the effects of amylin on food intake and body weight.