Norepinephrine, gamma-aminobutyric acid, and choline reuptake kinetics and the effects of ethanol in long-sleep and short-sleep mice.

Abstract

The reuptake characteristics of norepinephrine, gamma-aminobutyric acid (GABA), and choline were investigated in the long-sleep (LS) and short-sleep (SS) mouse lines. Kinetic analysis revealed no significant differences between lines in affinity (Km) or maximal velocity (Vmax) for norepinephrine and GABA measured in cortex and cerebellum or for choline measured in striatum and cortex. In vitro ethanol dose-response curves (0-1.7 M) for these neurotransmitters showed highly significant inhibition of reuptake except for reuptake of choline in cortex. All responses to ethanol were identical in both lines of mice. The magnitude of GABA reuptake inhibition was greater in cortex than in cerebellum. On the other hand, choline reuptake was very sensitive to ethanol in striatum, but was unaffected in cortex. These data suggest some regional specificity in ethanol's solubility. Inhibition of reuptake by ethanol concentrations greater than 0.86 M was determined to be irreversible and not due to hypertonic lysis. Our data are in complete agreement with previously published studies which suggest that ethanol inhibits neurotransmitter reuptake. However, since the LS and SS mice were selected for differential sensitivity to ethanol, and since we found no differences between lines in kinetic parameters or acute responses to in vitro ethanol, it appears that inhibition of neurotransmitter reuptake is not involved in the depressant effects of ethanol.