The locomotor activity of groups of three CD-1 female mice was increased by 1.0 and 2.0 g/kg ethanol, IP, was decreased during the first hour and increased during the second hour by 3.0 and 4.0 g/kg, and was decreased by 5.0 g/kg. The dose (2.0 g/kg) that caused the greatest increase in locomotor activity did not impair motor coordination, measured by the height of aerial righting in mice. Tests after oral administration of ethanol showed that the increase in locomotor activity of mice was not due to peritoneal irritation. The same dose (2.0 g/kg) did not increase the locomotor activity of C57BL/6J mice. Ethanol (0.1 to 3.0 g/kg) had no effect or decreased the locomotor activity of individual male Sprague-Dawley rats. These findings suggest that biological differences in strains and species of laboratory rodents contribute to the apparent variability of locomotor stimulation caused by ethanol. The presence or absence of an ethanol-induced increase in locomotor activity was not dependent on the sex or number of mice or rats tested. Intertrial-interval crossing by rats acquiring or performing an active avoidance task in a shuttle box was increased by ethanol. This action was dependent on the presentation of electric foot shock. Apomorphine (0.25 and 2.5 mg/kg) and fenmetozole (7.5 and 15.0 mg/kg) failed to inhibit the ethanol-induced increase in intertrial-interval crossing by rats, although these drugs have been shown previously to antagonize the ethanol-induced increase in the activity of mice ethanol treatment. The ethanol-induced increases in the spontaneous locomotor activity of CD-1 mice in photocell activity monitors and in intertrial-interval crosses in rats in a shuttle box task thus do not appear to share a common mechanism.

It is well known that the anxiolytic potential of ethanol is maintained during chronic exposure. We have confirmed this using a light-dark box paradigm following chronic ethanol ingestion via a liquid diet. However, cessation from chronic ethanol exposure is known to cause severe withdrawal anxiety. These opposing effects on anxiety likely result from neuro-adaptations of neurotransmitter systems within the brain regions regulating anxiety. Recent work highlights the importance of amygdala ligand-gated chloride channels in the expression of anxiety. We have therefore examined the effects of chronic ethanol exposure on GABA(A) and strychnine-sensitive glycine receptors expressed by acutely isolated adult rat lateral/basolateral amygdala neurons. Chronic ethanol exposure increased the functional expression of GABA(A) receptors in acutely isolated basolateral amygdala neurons without altering strychnine-sensitive glycine receptors. Neither the acute ethanol nor benzodiazepine sensitivity of either receptor system was affected. We explored the likelihood that subunit composition might influence each receptor's response to chronic ethanol. Importantly, when expressed in a mammalian heterologous system, GABA(A) receptors composed of unique alpha subunits were differentially sensitive to acute ethanol. Likewise, the presence of the beta subunit appeared to influence the acute ethanol sensitivity of glycine receptors containing the alpha(2) subunit. Our results suggest that the facilitation of GABA(A) receptors during chronic ethanol exposure may help explain the maintenance of ethanol's anti-anxiety effects during chronic ethanol exposure. Furthermore, the subunit composition of GABA(A) and strychnine-sensitive glycine receptors may ultimately influence the response of each system to chronic ethanol exposure.

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