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J Neurosci. 2014 Mar 19;34(12):4318-25. doi: 10.1523/JNEUROSCI.2260-13.2014.

Antipsychotic-like actions of the satiety peptide, amylin, in ventral striatal regions marked by overlapping calcitonin receptor and RAMP-1 gene expression.

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Neuroscience Training Program, University of Wisconsin-Madison, Medical Sciences Center, Madison, Wisconsin 53706, and Department of Psychiatry, University of Wisconsin-Madison, Wisconsin 53719.


Amylin is a calcitonin-related peptide co-secreted with insulin, which produces satiety through brainstem-localized receptors; however, its effects in forebrain are poorly understood. The nucleus accumbens shell (AcbSh) exhibits among the densest concentrations of high-affinity amylin binding; nevertheless, these receptors have not been explored beyond one study showing dopamine antagonist-like effects of intra-Acb amylin on feeding and associated behavior (Baldo and Kelley, 2001). Here, we investigated whether intra-Acb amylin signaling modulates prepulse inhibition (PPI), a measure of sensorimotor gating deficient in several illnesses including schizophrenia. First, in situ hybridization revealed marked anatomical gradients for both receptor activity-modifying protein-1 (RAMP-1) and calcitonin receptor gene (CT-R) expression in striatum [coexpression of these genes yields a high-affinity amylin-1 receptor (AMY1-R)], with highest overlap in the medial AcbSh. Intra-AcbSh amylin infusions in rats (0, 30, and 100 ng) reversed amphetamine (AMPH)-induced PPI disruption without affecting baseline startle; dorsal striatal amylin infusions had no effect. Coinfusion of AC187 (20 μg), an antagonist for AMY1-R, blocked the ability of amylin to normalize AMPH-induced PPI disruption, showing the specificity of AcbSh amylin effects to the AMY1-R. Intra-AcbSh AC187 on its own disrupted PPI in a haloperidol-reversible manner (0.1 mg/kg). Thus, AMY1-R may be a potential target for the development of putative antipsychotics or adjunct treatments that oppose metabolic side effects of current medications. Moreover, AMY1-Rs may represent a novel way to modulate activity preferentially in ventral versus dorsal striatum.


RAMPs; amylin receptor; dopamine; nucleus accumbens; schizophrenia; startle

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