Glycine enhances the central depressant properties of ethanol in mice

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The interaction between ethanol and glycine in the central nervous system was investigated in male Swiss-Webster mice. The loss of the righting reflex (LORR) was used as a measure of central nervous system depression. Mice were injected with ethanol (4.0 g/kg, IP), causing an ethanol-induced LORR. Immediately after the animals regained the righting reflex from ethanol administration, they received an intracerebroventricular (ICV) injection of saline or glycine (1, 15, 25, or 50 μmol/kg) in a volume of 5 μl. Upon ICV injection of glycine, the mice lost the righting reflex once again. This effect of glycine in the presence of ethanol occurred rapidly and in a dose-dependent manner. Glycine induced a return to the LORR of 12.6 ± 0.7, 24.5 ± 1.3, 32.8 ± 2.0, and 46.8 ± 4.5 min when doses of 1, 15, 25, and 50 μmol/kg, respectively, were injected. d-Serine (15, 25, or 50 μmol/kg), an amino acid precursor of glycine, was injected (ICV) after the animals regained the righting reflex following ethanol injection (IP). Serine caused a return to the LORR of 0.5 ± 0.5, 6.0 ± 1.0, and 6.5 ± 0.9 min when doses of 15, 25, and 50 μmol/kg, respectively, were injected. Strychnine was used to attenuate the ability of glycine and serine to cause a return to the LORR in the presence of ethanol. Strychnine, a competitive antagonist of glycine, significantly reduced the ability of glycine and serine to enhance the depressant action of ethanol. When glycine (50 μmol/kg), serine (50 μmol/kg), and stychnine (300 nmol/kg) were administered in the absence of ethanol, no significant return to the LORR was observed. Bicuculline, a GABA antagonist, was administered at a dose of 10 nmol/kg in combination with 25 μnol/kg of glycine. No significant reduction in glycine-induced return to the LORR was observed. This suggests that glycine is augmenting the effect of ethanol without stimulation of the GABAergic system. The results of this study indicate that glycine, an inhibitory neurotransmitter, can augment the central depressant properties of ethanol by acting on the strychnine-sensitive glycine receptor site.