Differential Effects of Monoaminergic Agonists on Alcohol Intake in Rats Fed a Tryptophan-Enhanced Diet

Abstract

The goal of the present study was to determine if enhancement of tryptophan levels in a nutritionally balanced liquid diet would affect alcohol intake in a two-bottle choice procedure. Furthermore, the monoaminergic agonists amphetamine, phentermine (dopaminergic- and noradrenergic-releasing drugs), and fenfluramine (a serotonin releaser) were administered to determine if these drugs reduced alcohol intake in animals fed the tryptophan-enhanced diet compared to those fed an alcohol-containing diet without added tryptophan. Amphetamine 0.5 and 2 mg/kg and phentermine 4 mg/kg selectively reduced alcohol intake in animals fed the tryptophan-enhanced diet; higher doses also reduced alcohol intake in animals fed the control alcohol diet. Three hours after drug administration, phentermine 2 and 4 mg/kg produced increases in consumption of the nonalcoholic diet in animals fed the control diet without affecting consumption in animals fed the tryptophan-enhanced diet. Finally, animals in the tryptophan-enhanced group gained less weight than those animals fed an identical diet without the added tryptophan. Neurochemical analysis revealed that the tryptophan-fed groups showed increased 5-HIAA concentrations and serotonin turnover in the striatum, hypothalamus, and frontal cortex compared to animals fed the control diet. The tryptophan-alcohol group also showed almost double the tryptophan levels in the hypothalamus compared to the tryptophan-isocaloric group. These results indicate that, whereas increasing tryptophan levels by itself was not sufficient to alter consumption of an alcohol-containing diet, the administration of monoaminergic agonists significantly interacted with tryptophan in a dose-dependent manner to reduce intake of an alcohol-containing diet without reducing intake of an isocaloric diet.