Role of enkephalinergic signaling in the limbic forebrain in modulating food reward

Opioid signaling promotes palatable food intake but endogenous signaling mediating this effect is poorly defined. We used behavioral, cytochemical, and electrophysiological approaches in wild‐type (WT) and preproenkephalin knockout (PPENK) mice to study the role of enkephalin in palatable food intake. Administration of the nonspecific opioid antagonist naltrexone (NTX) decreased intake of an array of palatable foods in WT mice; in PPENK mice, however, NTX administration elicited a slight trend toward increased consumption. This effect was not dependent upon caloric content, as it was observed for saccharin intake. Using cfos immunohistochemistry, we found that systemic NTX, while increasing cfos expression in the central nucleus of the amygdala (CeA) in WT mice, had no effect on cfos expression in the CeA of PPENK mice. To elucidate opioid effects on neural firing in the amygdala, we recorded from this brain region during intraoral infusion of appetitive or aversive tastants in WT and KO mice. Systemic NTX administration modulated baseline and taste‐evoked amygdalar firing in a population of neurons, including a subset that responded differentially to sucrose versus quinine. Our results demonstrate that tonic enkephalinergic signaling modulates taste‐sensitive neural responses in the amygdala.