Pharmacologic Control of Feeding

Abstract

Several forces have combined to focus research on phenethylamines. Modern re­ search in neuroscience has concentrated on the neuroanatomy and neurochemistry of brain monoamines and their roles in psychosis, schizophrenia, anorexia nervosa, and hyperphagia. Phenethylamines such as amphetamine, fenfl uramine, and phenyl­ propanolamine have the same basic structures as the monoamine neurotransmitters; therefore they have become useful tools in research and therapy. Phenethylamines are well known-some are infamous-for the treatment of obesity which has become prevalent in food-rich nations. Because amphetamine is now illegal in many countries, other anti-obesity drugs such as fenfl uramine have been sought. Amphetamine is primarily catecholaminergic and fenfl uramine is primarily sero­ tonergic; therefore it was our working hypothesis that somewhere in the brain, catecholamine and serotonin neurons participate in the inhibition of feeding. Deplet­ ing the appropriate neurotransmitters should release feeding from inhibition and thereby lead to obesity. Our work has led to several findings including the following: (0) experimental obesity can follow adrenergic depletion with 6-hydroxydopamine; (b) obesity can also follow serotonergic depletion with parachlorophenylalanine; (c) adrenergic depletion causes a decrease in amphetamine anorexia, and this may be coupled with an increase in fenfluramine anorexia; (d) phenylpropanolamine may influence feed­ ing in part by altering glucose utilization, and (e) electrical self-stimulation and stimulation-escape at certain brain sites can be used to assess the arousal and anorectic properties of anti-obesity drugs. These findings provide new models for the study and treatment of obesity. There has developed a distinction between two kinds of hyperphagia �ased on monoamine