Effects of aging on the opioid modulation of feeding in humans

OBJECTIVES: To determine whether aging is associated with a reduction in the opioid modulation of feeding, which may be important in the pathogenesis of the "anorexia of aging." DESIGN: Three studies on separate days, in randomized order and double-blind fashion. SETTING: Clinical Human Research Laboratory, Department of Medicine, RAH, Adelaide, Australia. PARTICIPANTS: Twelve older (5 male/7 female) (age 65-84) and 12 young (5 male/7 female) (age 20-26) healthy subjects. INTERVENTION: Subjects received in double-blinded random order, intravenous bolus (10 minutes) and then continuous (140 minutes) infusions of saline (control), naloxone low dose (LD) (bolus 27 mug/kg continuous 50 mug/kg/hr), or naloxone high dose (HD) (bolus 54.5 mug/kg; continuous 100 mug/kg/hr). MEASUREMENTS: After 120 minutes, subjects were offered a buffet meal, and their energy intake was quantified. Hunger, fullness, nausea, and drowsiness were assessed using visual analogue scales. RESULTS: The naloxone LD and HD infusions had no significant effect on ratings of hunger, fullness, or nausea, but increased drowsiness (P < .01) compared with the control infusion in both age groups. Older subjects ate less (P < .001) at the buffet meal than young subjects during all three infusions. Naloxone infusions reduced energy intake compared with control (P < .001), LD by 13.2 +/- 5.0% and HD by 10.7 +/- 5.0%, with no difference between the doses (P = .71). Overall, naloxone suppressed energy intake in both young and older subjects (P < .01). This suppression was slightly, but not significantly, greater in young than in older subjects (mean of LD and HD 16.4 +/- 4.9% vs 7.5 +/- 4.9%, P = .42), because of a trend to reduced suppression in older women. CONCLUSIONS: We conclude that healthy older adults retain their sensitivity to the suppressive effects of naloxone on food intake. Possible gender differences in this sensitivity warrant further investigation. A decline in opioid activity is unlikely to contribute substantially to the physiological anorexia of aging observed in older people.