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ABSTRACT: 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." Three studies on separate days, in randomized order and double-blind fashion. Clinical Human Research Laboratory, Department of Medicine, RAH, Adelaide, Australia. Twelve older (5 male/7 female) (age 65-84) and 12 young (5 male/7 female) (age 20-26) healthy subjects. 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 microg/kg; continuous 50 microg/kg/hr), or naloxone high dose (HD) (bolus 54.5 microg/kg; continuous 100 microg/kg/hr). 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. 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. 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.