Glycine enhances the central depressant properties of ethanol in mice.
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 mumol/kg) in a volume of 5 microliters. 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 mumol/kg, respectively, were injected. D-Serine (15, 25, or 50 mumol/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 mumol/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Williams
K L
KL
Hahnemann University, School of Medicine, Department of Pharmacology, Philadelphia, PA 19102, USA.
Ferko
A P
AP
Barbieri
E J
EJ
DiGregorio
G J
GJ
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004357:Drug Synergism; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005998:Glycine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D004856:Postural Balance / Q000187:drug effects; D012694:Serine / Q000494:pharmacology; D013331:Strychnine / Q000494:pharmacology
D002492:Central Nervous System Depressants; D000431:Ethanol; D012694:Serine; D013331:Strychnine; D005998:Glycine; D001640:Bicuculline