Central melanocortins modulate mesocorticolimbic activity and food seeking behavior in the rat

Abstract

The hypothalamic melanocortin system is known for its role in regulating energy homeostasis through it actions within hypothalamic brain centers. However, emerging evidence suggests that this system regulates addictive behaviors through signaling within mesolimbic neurons. Here, we hypothesized the melanocortin system modulates feeding behavior through its actions on mesolimbic neurons. In particular, we predicted that central administration of the melanocortin antagonist agouti-related peptide (AgRP) would activate midbrain dopamine neurons, increase mesolimbic dopamine turnover, and alter food seeking behaviors. We found that intraventricular administration of agouti-related peptide increased neuronal activation within midbrain dopamine neurons in addition to increasing dopamine turnover in the medial prefrontal cortex. Additionally, using the conditioned place preference paradigm to assay food seeking behavior, we report that central injection of agouti-related peptide attenuates the acquisition of a conditioned place preference for sucrose, but not high fat diet. These results suggest that the melanocortin system is capable of regulating mesocorticolimbic activity and food seeking behavior.

Figure 1

Dopamine turnover in the A) medial prefrontal cortex (mPFC) or B) nucleus accumben (NAcc) ninety minutes after a I3vt AgRP injection and c-Fos immunoreactivity in TH positive neurons following C) saline or D) 1nmol AgRP injection. arrows indicate co-localization of c-Fos in TH neurons; c-Fos appears in red, TH positive neurons are labeled in green.* = p<0.05.

Figure 2

A) Conditioned place preference score after 6 conditioning sessions with HFD or B) sucrose in rats injected with I3vt AgRP during training. CPP score is expressed as percentage of total time spent in paired chamber on test day only * = p<0.05.