D-cycloserine blocks the effects of ethanol and HA-966 in rats tested in the elevated plus-maze.
Previous studies from our laboratory have shown gender-related behavior in rats tested in the elevated plus-maze under the influence of ethanol and other drugs. The present study investigated the effects of pretreatment with the NMDA-receptor partial agonist at the glycine site D-cycloserine (DCS; doses 3 to 9 mg/kg for females; 3 to 12 mg/kg for males, intraperitoneally) on the effects of ethanol (1.2 g/kg, i.p.; 14% w/v) and (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA-966; 2 or 4 mg/kg, i.p.), an antagonist at the glycine site of the NMDA receptor complex in rats submitted to the elevated plus-maze test. The results showed that DCS, at doses that did not affect the behavior of control animals, significantly (p < 0.05) prevented the increase in the percentage of open-arm entries and the time spent in the open arms of elevated plus-maze test induced by ethanol, exhibiting a U-shaped dose-response curve. Similarly, DCS blocked the anxiolytic effects of HA-966 in animals of both gender. Data confirm our previous results, suggesting that the NMDA-receptor system contributes significantly to the anxiolytic effect of ethanol. Furthermore, the similarity between the blockade by DCS of anxiolysis induced either by ethanol or by HA-966 strengthens the suggestion that ethanol acts on the glycine site of the NMDA receptor complex.
Moraes Ferreira
V M
VM
Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Morato
G S
GS
D000818:Animals; D001007:Anxiety / Q000517:prevention & control*; D001522:Behavior, Animal / Q000187:drug effects*; D003523:Cycloserine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D018690:Excitatory Amino Acid Agonists; D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D003523:Cycloserine; C001369:1-hydroxy-3-amino-2-pyrrolidone