Electrophysiological responses to ethanol, pentobarbital, and nicotine in mice genetically selected for differential sensitivity to ethanol

Cortical electroencephalographic (EEG) changes induced by ethanol (4.3 and 1.4 g/kg, ip), pentobarbital (50 and 16 mg/kg), and nicotine (1.0 g/kg) were examined in long-sleep (LS) and short-sleep (SS) mice that were genetically selected for differential sleep times induced by a hypnotic dosage of ethanol. Ethanol (4.3 g/kg) caused EEG changes that paralleled the behavioral differences, whereas no differences between selected lines were observed following the activating dose (1.4 g/kg). Data support the notion that the known difference in ethanol sleep times is due not to greater SS sensitivity to ethanol activation but rather to greater LS sensitivity to ethanol hypnosis. No differences between selected lines were observed following 50 mg/kg pentobarbital, which again parallels previous behavioral data. The SS mice were more responsive to pentobarbital activation (16 mg/kg). Nicotine more severely reduced EEG power and heart rate in LS mice; a continuous iv infusion of nicotine elicited a distinct pattern of behavioral stereotypy for each selected line, with more profound motor and reflex depression in LS mice. The lines do not differ in rate of nicotine metabolism, hence they must differ in central nervous system sensitivity to nicotine. Thus, lines of mice selectively bred for differential sensitivity to ethanol also display marked differences in electrophysiological and behavioral responses to nicotine.