Effect of Agouti-related protein on development of conditioned taste aversion and oxytocin neuronal activation

Agouti-related protein (Agrp) is an orexigenic peptide that acts as an antagonist of the melanocortin-3 and -4 receptors. Initial studies suggest similarities between the effects of Agrp and opioid peptides on ingestive behavior. Given these observations, we examined whether Agrp, similarly to opioids, alleviates conditioned taste aversion (CTA) generated by peripheral injection of LiCl. Agrp (1 nmol) delivered to the lateral cerebral ventricle, a dose known to cause orexigenic effects, was shown to partially block acquisition of LiCl-induced CTA. Agrp also decreased the percentage of c-Fos-positive oxytocin neurons induced by LiCl in the hypothalamic paraventricular and supraoptic nuclei. Inhibitory effects of Agrp on acquisition of CTA and aversion-associated activation of oxytocin neurons parallel what has previously been shown with opioid receptor agonists.