Effects of oxytocin on feeding suppression and neuronal activity in aged mice

Abstract

Many studies have shown that, compared to younger adults, old individuals show a different sensitivity to various pharmacological treatments. This phenomenon stems from a plethora of physiological and pathophysiological changes associated with aging, from hormonal regulation to brain functioning. Yet, most animal and human studies do not focus on effects of experimental molecules in aged individuals. This includes drugs that affect appetite and body weight, among which, only a handful have been investigated in the context of aging. One appetite suppressant that has garnered recent attention is oxytocin (OT). In younger adult humans and laboratory animals, peripheral administration of OT reduces eating to satisfy hunger as well as the intake strictly for palatability (pleasure). The effects of OT on food intake in aged individuals are unknown. Thus, the current project was aimed at elucidating the effect of intraperitoneally (IP) injected OT on consumption of standard and palatable food in aged male mice. This effect was compared to the outcome of the OT treatment in younger adults. In order to identify differences in central mechanisms triggered by OT treatment in aged versus adult mice, the feeding studies were followed by the analysis of OT-induced activity of brain sites involved in appetite control in these animals. Brain activation was assessed by an immunohistochemical detection of an immediate-early gene product, c-Fos, in relevant brain areas. IP OT decreased food consumption in aged and adult male mice. The lowest effective dose in supressing consumption of solid standard and palatable diets in aged animals was 0.3 mg/kg, whereas a higher dose of 1 mg/kg was required to elicit the same response in younger adults. Furthermore, OT in aged mice supressed palatable sucrose solution intake at 1 mg/kg and milk at 0.1 mg/kg, whereas in young adults, sucrose and milk intakes were supressed by 1 mg/kg OT. The effective dose of 0.3 mg/kg OT in aged animals increased activation of the paraventricular nucleus, central nucleus of the amygdala, nucleus tractus solitarius, and arcuate nucleus and decreased activation of ventromedial nucleus of the hypothalamus and dorsomedial hypothalamus. On the other hand, the 0.3 mg/kg dose in adults resulted in increased c-Fos IR only in paraventricular nucleus, central nucleus of the amygdala, and nucleus tractus solitarius and a decrease only in the ventromedial nucleus of the hypothalamus. The results allow me to conclude that intraperitoneal OT is an effective appetite suppressant in aged individuals, however, a lower dose of the drug is sufficient to generate a decrease in consumption at an old age. This likely stems from a broader circuit of feeding-related brain sites activated by the low dose of OT in aged animals compared to the younger adults.