Satiety and Reward: Dichotomy of Cocaine‐ and Amphetamine‐Regulated Transcript Peptide's Function During Binge Eating

Abstract

Since cocaine‐ and amphetamine‐regulated transcript peptide (CART) mediates feeding as well as reward, we investigated its role in binge eating (BE), a clinical condition which disrupts satiety. BE was induced in rats by providing 2‐h access to high fat‐sweet palatable diet (HFSPD) on alternate days for 4 weeks. Effect of drug treatments on HFSPD intake and CART immunoreactive profile in reward and satiety regulating nuclei was studied. Rats fed on HFSPDshowed explosive BE. Higher doses of CART or rimonabant was required to reduce BE, as compared to that of normal chow intake in naïve rats. At the mid‐point during BE, CART immunoreactivity was significantly up‐regulated in the arcuate (ARC), lateral (LH) nucleus, paraventricular nucleus of thalamus (PVT), and nucleus accumbens shell (AcbSh) but not in the paraventricular (PVN) nucleus. At mid‐binge time‐point, the rimonabant treated rats showed increased CART expression in ARC and LH, while that in PVT and AcbSh was decreased. Increase in co‐expression of CART and synaptophysin in LH and cornu ammonis 1 of hippocampus suggested neuroplastic changes in CART system in BE rats. We suggests that BE enhanced the CARTergic signaling in the ARC/LH‐PVT‐AcbSh axis and suppressed the ARC‐PVN pathway. The net result may be the reward pathway overriding the satiety circuit. Opposite may happen following treatment with rimonabant. Further, CART seems to participate in the memory formation pertaining to HFSPD‐related reward.