Cocaine- and amphetamine-regulated transcript peptide increases spatial learning and memory in rats

Abstract

Aim: We investigated the involvement of cocaine- and amphetamine-regulated transcript peptide (CART) in spatial learning and memory. Main methods: Rats were intracerebroventricularly injected with CART or CART-antibody, with or without intraperitoneal scopolamine, for a period of 4 days, during which they were subjected to the acquisition protocol in Morris water maze (MWM). In retrieval protocols, at 24 h and 15 days post-acquisition time points similar treatments were given to trained rats and subjected to MWM. The response of endogenous CARTsystemtothetraining aswellas retrieval sessions in MWMwasevaluatedwithimmunohistochemistry. Key findings: CART-administered rats showed a significant reduction in escape latency from day 1 through 4 days of acquisition; the rats spent more time in the platform quadrant in MWM during the retrieval protocol. CART-antibody or scopolamine produced an opposite effect. The effects of scopolamine were attenuated by CART, and potentiated by CART-antibody. CART-immunoreactivity in the arcuate and paraventricular nuclei, central nucleus of amygdala, bed nucleus of stria terminalis, accumbens shell, dentate gyrus (DG), and thalamic paraventricular nucleus (PVT), but not in the cornu ammonis 1–3 of hippocampus, wassignificantly increased following 4 days of training, and at 24 h retrieval time point in MWM.Thechanges were blocked by scopolamine. At 15 days retrieval time point, the immunoreactivity profiles resembled those in naïve control. Significance: While CART seems to promote spatial learning and memory, navigational experiences in MWM up regulates the endogenous CART systems in extended amygdala, hypothalamus, DG and PVT.