Free‐Choice Alcohol Consumption in Mice After Application of the Appetite Regulating Peptide Leptin

Abstract

Leptin has been shown to regulate food intake and energy expenditure. Very recently, associations of elevated leptin plasma levels during alcohol withdrawal with alcohol craving have been observed in humans. Therefore, we tested the hypothesis that the application of exogenous leptin modulates voluntary alcohol consumption in mice. Sixteen mice (129/Sv x C57BL/6J) were habituated to ethanol consumption over a time period of 3 months. After a basal 2-week free-choice drinking phase, mice were separated into two groups (n = 8) according to weight and alcohol consumption. They received recombinant leptin (1 mg/kg) versus saline intraperitoneally daily for 10 days. After 4 days of free-choice consumption of ethanol (16% v/v) versus water, ethanol was withdrawn at day 4 and replaced at day 6 to test the occurrence of an alcohol deprivation effects. Fluid intake was evaluated by controlling the weight of the drinking tubes daily. Free-choice ethanol consumption after withdrawal was significantly elevated in mice after intraperitoneal injection of 1 mg/kg leptin (alcohol deprivation effect), but not during basal drinking. We suggest that leptin may enhance motivation for alcohol consumption in habituated mice after alcohol withdrawal.