Chronic administration of anorexigenic substances to experimental animals by injections or continuous infusion typically produces no effect or a transient reduction in daily food intake and body weight. Our aim was to identify an intermittent dosing strategy for intraperitoneal infusion of salmon calcitonin (sCT), a homolog of amylin that produces a sustained 25–35% reduction in daily food intake and adiposity in diet-induced obese rats. Rats (649 ± 10 g body wt, 27 ± 1% body fat), with intraperitoneal catheters tethered to infusion swivels, had free access to a 45% fat diet. Food intake, body weight, and adiposity during the 7-wk test period were relatively stable in the vehicle-treated rats ( n = 16). None of 10 sCT dosing regimens administered in succession to a second group of rats ( n = 18) produced a sustained 25–35% reduction in daily food intake for >5 days, although body weight and adiposity were reduced by 9% (587 ± 12 vs. 651 ± 14 g) and 22% (20.6 ± 1.2 vs. 26.5 ± 1.1%), respectively, across the 7-wk period. The declining inhibitory effect of sCT on daily food intake with the 6-h interinfusion interval appeared to be due in part to an increase in food intake between infusions. The declining inhibitory effect of sCT on daily food intake with the 2- to 3-h interinfusion interval suggested possible receptor downregulation and tolerance to frequent sCT administration; however, food intake increased dramatically when sCT was discontinued for 1 day after apparent loss of treatment efficacy. Together, these results demonstrate the activation of a potent homeostatic response to increase food intake when sCT reduces food intake and energy reserves in diet-induced obese rats.
Effect of increasing intraperitoneal infusion rates on bupropion hydrochloride-induced seizures in mice
