The
drug combination of
phentermine plus
fenfluramine has been used clinically in both the treatment of
obesity and
alcoholism. The aim of the current study was to assess the interaction of the two drugs on consumption of both an alcohol-containing and a nonalcoholic diet. Furthermore, the efficacy of the
drug combination on suppression of withdrawal
seizures was determined. Animals were either maintained on a 6% alcohol-containing diet, free-fed an isocaloric control, or pair-fed the control diet. It was observed that, with regard to
body weight growth curves, alcohol provides about 2.5 kcal/g. Both
phentermine and
fenfluramine caused a decrease in consumption 1 h after administration; however, during the next 23 h, 4 mg/kg
phentermine significantly increased consumption of all diets. At doses of 1 and 2 mg/kg,
fenfluramine selectively reduced consumption of the alcohol-containing diet as compared to the isocaloric diets. Lower doses of
fenfluramine blocked the increases in consumption induced by
phentermine. Furthermore, in animals fed the nonalcoholic diet, the
drug combination of 2 mg/kg
fenfluramine plus 8 mg/kg
phentermine produced a 63-82% reduction in consumption, an effect not seen when either
drug was administered alone. This greater than additive effect was also seen in the earlier time periods in animals pair-fed the control diet. Neurochemical analysis from these animals revealed that the alcohol-dependent animals displayed a significant reduction of
DOPAC and
5-HIAA levels in the striatum, frontal cortex, and hypothalamus after a 9-h withdrawal period, further implicating the serotonergic and dopaminergic systems in mediation of
withdrawal symptoms and alcohol craving. Finally, 8 mg/kg
phentermine plus 8 mg/kg
fenfluramine completely abolished
alcohol withdrawal seizures, compared to a 78% rate in saline treated rats. In conclusion, the coadministration of
phentermine plus
fenfluramine produced a moderate reduction of alcohol consumption and was completely effective at reducing
alcohol withdrawal seizures.