Effects of naltrexone on energy- and palatability-driven consumption and neuronal activation in feeding-related forebrain areas: relationship with age

Abstract

Intake of energy as well as interest in palatable foods diminish during the ageing process. One of the likely reasons underlying this phenomenon is an age-related decrease in the opioid tone in the brain. To further substantiate this hypothesis, the current project was aimed to elucidate the effects of an opioid receptor antagonist, naltrexone, on energy- and palatability-driven consumption in 6-, 16- and 22-month old mice and on the activation of feeding-related forebrain circuitry (hypothalamic and accumbal) in adult vs old male mice. The findings indicate that old (22-month old) mice exhibit diminished responsiveness to anorexigenic properties of naltrexone in deprivation-induced intake of “bland” chow and eating for reward (consumption of low-/non-calorie solutions containing sucrose and saccharin). Interestingly, in the pilot studies performed in rats, sensitivity to anorexigenic action of naltrexone was similar at two different phases of adult lifespan prior to reaching the old age (2 months and 18months). The c-Fos immunoreactivity analysis in mice indicated that unlike in adult animals at a younger age, in old animals, naltrexone fails to activate the nucleus accumbens shell, the ventromedial and hypothalamic nuclei, and it activates the lateral hypothalamus. These c-Fos data provide an insight into neural responsiveness changes that might underscore differential feeding regulatory outcomes seen after naltrexone administration in old animals compared to their adult yet younger counterparts.