The main effect of cocaine- and amphetamine-regulated transcript (CART) peptide on hypothalamic neuronal activity depends on the nutritional state of rats

The anorectic and catabolic action of CART is primarily mediated by the hypothalamus. The study proved the hypothesis that neurons of the hypothalamic regulatory system of body weight differentially react to CART in dependence of the nutritional state of the animal: overweight, fed or short-term fasting.

Single unit activity was extracellularly recorded in brain slices. The action of CART was studied in brains of 1. overweight adult rats previously subjected to early postnatal overfeeding in small litters (SL), compared to control litters, 2. normal rats that were deprived of food for 24 h, compared to fed rats.

Hypothalamic dorsomedial neurons of controls, but not SL rats were significantly excited by CART, ventromedial neurons of SL rats were significantly inhibited. Also neurons of hungry rats were significantly inhibited.

Controls and overweight SL as well as fed and hungry rats differed significantly in the neuronal effects of CART. The predominant effect of the peptide did neither depend on weight nor on age of animals, but on neonatal development or nutritional state.

The increase in inhibition by CART of ventromedial and dorsomedial neuronal activity could in vivo contribute to increased food intake and reduced energy expenditure of overweight SL as of hungry rats. Since leptin is able to change synaptic wiring and the expression of excitatory and inhibitory synapses already within short time, the increased expression of inhibitory responses to CART may reflect a general mechanism in adaptation of neuronal regulatory systems to the nutritional state, in fed, adult small-litter rats acquired during the postnatal critical differentiation period, thus leading to permanently altered function.