Effects of MK-801 and ethanol combinations on memory consolidation in CD1 mice: involvement of GABAergic mechanisms.
In the present research the effect of the noncompetitive N-methyl-d-aspartate receptor antagonist MK-801 and ethanol combinations on memory consolidation and the involvement of GABAergic mechanisms in this effect were investigated in CD1 mice injected intraperitoneally with the drugs immediately or 120 min after training in a one-trial inhibitory avoidance apparatus and tested for retention 24 h later. The results showed that (a) the retention performances of mice were impaired in a dose-dependent manner by immediate posttraining MK-801 (0.2 and 0.3, but not 0.1 mg/kg) and ethanol (1 and 2, but not 0.5 g/kg) administrations; (b) an otherwise ineffective dose of MK-801 (0.1 mg/kg) enhanced the deleterious effect exerted by ethanol (1 and 2 g/kg); (c) an otherwise ineffective dose of muscimol (0.5 mg/kg) enhanced, while otherwise ineffective doses of picrotoxin (0.25 mg/kg) or bicuculline (0.1 mg/kg) antagonized, this effect; and (d) no effect was observed when the treatments were carried out 120 min after training, suggesting that the effects observed following immediate posttraining administrations were due to the influence on the consolidation of memory. From these experiments it is evident that (a) MK-801 enhances ethanol's effects on memory consolidation and (b) GABAergic mechanisms are involved in this effect.
Aversano
Marco
M
Istituto di Psicobiologia e Psicofarmacologia del CNR, Viale Marx 15, 00137 Rome, Italy.
Ciamei
Alessandro
A
Cestari
Vincenzo
V
Passino
Enrica
E
Middei
Silvia
S
Castellano
Claudio
C
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D018079:Receptors, GABA / Q000378:metabolism*
D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists; D018079:Receptors, GABA; D000431:Ethanol; D016291:Dizocilpine Maleate