d-Cycloserine Blocks the Effects of Ethanol and HA-966 in Rats Tested in the Elevated Plus-Maze

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 1997-12, Vol.21 (9), p.1638-1642
• Main Authors: Moraes Ferreira, Vânia Maria, Morato, Gina Struffaldi
• Format: Article
• Language: English
• Subjects: (±)-HA-966; Alcoholism and acute alcohol poisoning; Animals; Anxiety; Anxiety - prevention & control; Behavior, Animal - drug effects; Biological and medical sciences; Cycloserine - pharmacology; d-cycloserine; Dose-Response Relationship, Drug; Ethanol; Ethanol - antagonists & inhibitors; Ethanol - pharmacology; Excitatory Amino Acid Agonists - pharmacology; Female; Gender; Male; Maze Learning - drug effects; Medical sciences; Pyrrolidinones - pharmacology; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate - drug effects; Toxicology
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/j.1530-0277.1997.tb04501.x

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, ip; 14% w/v) and (±)‐3‐amino‐1‐hydroxy‐2‐pyrrolidone (HA‐966; 2 or 4 mg/kg, ip), 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.