Forebrain agouti-related protein (AgRP) injections increase appetitive but not consummatory feeding behaviors in the rat.

Abstract

Agouti-related protein (AgRP), an endogenous melanocortin receptor inverse agonist, stimulates feeding. Exogenous application promotes ingestion over an extended multi-day period. In the current study, several methods were employed to determine the effects of lateral (LV) or third ventricle (3 V) injections of AgRP on appetitive and consummatory measures of feeding behavior. In Experiment 1, rats were injected with AgRP (1 nM/3 μl) or vehicle into either 3V or LV, 2 h prior to 30 min enclosure in one side of a conditioned place preference test chamber, over 3 consecutive days. On day 4, rats were tested for 30 min place preference. In Experiment 2, rats received LV injection of AgRP/vehicle 2 h prior to 4 h scheduled access to a lick spout containing 0.05 M sucrose. The time of each lick was recorded. In Experiment 1, rats receiving LV but not 3 V AgRP injections exhibited a significant preference for the sided associated with AgRP ( p <0.001). AgRP, LV or 3 V, also significantly increased chow intake over training days ( p <0.05). In Experiment 2, LV AgRP significantly increased 4 h sucrose intake by ∼40% ( p <0.05). This effect was entirely mediated by a comparable increase in meal frequency ( p <0.05). There was no effect of AgRP on any measures of intra-meal microstructure, including average meal size, meal duration, ingestion rate, initial lick rate, or burst size or number. These results are consistent with the finding that AgRP enhances foraging more than feeding in the hamster, while they contrast the effects of hindbrain melanocortin antagonist injections in rat, which were limited to meal size rather than frequency. Together, the results suggest multiple sites of AgRP action on separate aspects of feeding. Supported by NIH DK 59836 and DC 07389.