Behavioral processes underlying the intake suppressive effects of melanocortin 3/4 receptor activation in the rat

Abstract.

Rationale: Central application of MTII, a melanocortin 3/4 receptor agonist, reduces food intake. The behavioral mechanisms underlying the anorexia, however, have not been evaluated. Objectives: We examined the ingestive behavioral effects of MTII at the microstructural level using two complementary approaches. Methods: Rats were given daily 2-h sessions during which they drank 12.5% glucose solution; the time of occurrence of each lick event was recorded. We compared rats' glucose intake 30 min after the fourth ICV injection of 0.1, 0.33, and 1.0 nmol MTII or vehicle. The licking patterns were examined to discern effects on parameters related to taste processes and others related to post-ingestive inhibitory feedback. A second experiment directly analyzed the effect of MTII on motor performance by examining whether drug treated rats would, like controls, adjust licking output to maintain meal size when lick volume was shifted from 8 to 4 µl. Results: Meal size was reduced by MTII in a dose-dependent manner (20–50%) in both experiments. Rats treated with MTII compensated for decreased lick volume by substantially increasing the number of licks emitted. Licking parameters associated with taste evaluation were not significantly affected by MTII, whereas parameters associated with post-ingestive inhibition varied as a function of treatment. Conclusions: Results suggest that MTII reduces intake by amplifying post-ingestive feedback inhibition. That MTII-treated rats increase the number of licks emitted in response to the lick volume reduction discounts the suggestion that intake inhibition is secondary to disruption of motor performance.