An investigation of tolerance to the actions of leptogenic and anorexigenic drugs in mice.

This study compared the effects of chronic administration of anorexigenic drugs on weight loss in mice. Tolerance to the effects of peripheral anorexigenic peptides, viz. cholecystokinin-octapeptide and bombesin, developed rapidly. Morphine, cocaine and dehydroepiandrosterone-sulfate caused weight loss and appeared similar to d-amphetamine in mechanisms of action. A high dose of fluoxetine (25 mg/kg) proved to be a potent leptogenic agent but was also associated with death in some animals. A lower dose of fluoxetine (5 mg/kg) was associated with the development of tolerance. Calcitonin, a potent anorexigenic agent, did not produce weight loss and tolerance to its anorectic effect had developed by 10 days. Animals varied widely in their individual responsiveness to a given drug. Peripheral administration of peptide YY caused weight loss. We conclude that acute or chronic effects of agents on food intake do not necessarily predict effects on body weight. However, neurotransmitters that enhance feeding centrally appear to cause weight loss when administered peripherally.