Antidepressant drugs are reported to decrease the resting metabolic rate and increase body mass of depressed patients. Increased body mass may be partly related to the decrease in metabolic rate. The change in energy budgeting that follows chronic antidepressant treatment may be related to the behavior-activating effects of the drugs. This project investigates the functional ( e.g. thermoregulatory) and endocrine aspects of altered body mass. Previously we found that chronic inhibition of type A monoamine oxidase (MAO) in Syrian hamsters with the antidepressant drug clorgyline a) prevents normal weight gain, b) decreases body lipid content, c), decreases oxygen and food consumption, and d) decreases the level of peritoneal and brain temperature. We also found that chronic clorgyline treatment alters adrenal, kidney, testis and brown adipose tissue (BAT) masses, suggesting that clorgyline-treatment might have significant endocrine effects. In light of these organ data, as well as reports that melatonin and corticosteroids affect thermoregulation, we examined the daily variation of cortisol corticosterone, ACTH and melatonin in clorgyline-treated hamsters to assess their possible roles as mediators of clorgyline's effects on thermoregulation . Chronic clorgyline treatment was found to elevate pineal melatonin, serum ACTH, cortisol and corticosterone. The observation that chronic clorgyline decreases the mass of BAT and elevates levels of corticosteroids is consistent with reports that chronic corticosterone administration decreases functional activity (GDP binding) of BAT. In contrast, although melatonin is reported to activate BAT thermogenesis, elevation of melatonin levels was not associated with increased BAT mass. Thus, in Syrian hamsters, chronic antidepressant drug treatment with the MAOI clorgyline may alter thermoregulation by corticosteroid-mediated inhibition of non-shivering thermogenesis (NST). In collaboration with Dr. Christopher Gordon, we explored effects of clorgyline on autonomic and behavioral aspects of thermoregulation in Syrian hamsters. At cold ambient temperatures, clorgyline elevated metabolic rate and motor activity, possibly to compensate for the loss of insulative body fat and/or diminished NST. When placed on a thermal gradient for 24 hours, clorgyline-treated hamsters tended to select cooler ambient temperatures, and the circadian rhythm in thermal preference that is normally present was absent. Drug-treated hamsters also spent less time in the thermoneutral portion of the thermocline, suggesting that these animals' capacity to thermoregulate was less finely tuned than control animals.
