Leptin fails to reduce ethanol intake in Marchigian Sardinian alcohol-preferring rats

Abstract

Leptin, a hormone secreted by the adipocytes and involved in feeding and energy balance control, has been proposed to modulate alcohol craving in mice and humans. This study evaluated whether leptin modulates alcohol intake in Marchigian Sardinian alcohol-preferring (msP) rats. Rats were offered 10% ethanol either 2 h per day at the beginning of dark period of the 12:12 h light/dark cycle, or 24 h per day. Leptin was injected into the lateral ventricle (LV), the third ventricle (3V), or intraperitoneally (IP) once a day, 1 h before the onset of the dark period. Neither acute nor chronic (9 days) leptin injections (1 or 8 μg per rat) into the LV or 3V modified ethanol intake in male msP rats, offered ethanol 2 h per day. Chronic LV injection of leptin (8 or 32 μg per rat in male rats and 8 or 16 μg per rat in female rats for 7 days), or chronic IP injections of leptin (1 mg/kg in male rats for 5 days) failed to modify the intake of ethanol, offered 24 h per day. Finally, chronic LV leptin injections (8 or 32 μg per rat for 12 days) did not modify ethanol intake in male msP rats, adapted to ad libitum access to ethanol and then tested after a 6-day period of ethanol deprivation. In contrast, in most of these conditions leptin significantly reduced food intake. These data do not support a role for leptin in alcohol intake, preference, or craving in msP rats.