The purpose of the present study was to determine whether the motor impairment (myorelaxation/
ataxia) induced by
excitatory amino acid receptor antagonists was exaggerated by pretreatment with
ethanol. The results were compared with those of
gamma-aminobutyric acid(A) (
GABA(A)) receptor positive modulators alone and in combination with
ethanol. The
excitatory amino acid receptor antagonists,
dizocilpine [(+)-
MK-801; (5R,1OS)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten+ ++-5,10-
imine], (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-
phosphonic acid (
CPP),
LY 326325 [(-)-(3S,4aR,6R,8R)-6-[2-(1(2)H-tetrazol-5-yl)-ethyl]-dec ahydroisoquinaline-3-carboxylic
acid],
LY 300164 [7,8-methylenedioxy-1-(4-aminophenyl)-4-methyl-3-acetyl-4,5-dihydro-2,3-
benzodiazepine], and
ACEA 1011 (5-chloro-7-trifluoromethyl-1,4-dihydro-2,3-quinoxalinedione) produced dose-dependent myorelaxation/
ataxia in mice as determined using the horizontal wire assay. Their behaviorally toxic doses (TD(50)s) were 0.41, 5.8, 33.0, 5.9, and 31.0 mg/kg, respectively, when administered alone i.p. In the presence of a sub-ataxic dose of
ethanol (1.5 g/kg, i.p.), the TD(50)s of the
excitatory amino acid antagonists were 0.13, 1.8, 10.4, 1.3, and 14.0 mg/kg, respectively. Similarly, the
GABA(A) receptor positive modulators,
pregnanolone,
chlordiazepoxide, and
pentobarbital exhibited TD(50)s of 20.8, 4.6, and 29.7 mg/kg, respectively, when administered alone and 2.7, 0.3, and 11.4 mg/kg, respectively, when administered in the presence of
ethanol. Thus, similar to the
GABA(A) receptor positive modulators,
excitatory amino acid receptor antagonists exhibit the propensity to interact with
ethanol and to have their motor side-effects exaggerated.