Effect of D-cycloserine on rapid tolerance to ethanol

• Published in: Pharmacology, biochemistry and behavior Vol. 45; no. 4; pp. 983 - 986
• Main Authors: Khanna, J.M., Kalant, H., Shah, G., Chau, A.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.1993; Elsevier Science
• Subjects: (+)MK-801; Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Cycloserine - antagonists & inhibitors; Cycloserine - pharmacology; D-Cycloserine; Dizocilpine Maleate - pharmacology; Drug Tolerance; Ethanol; Ethanol - pharmacology; Male; Medical sciences; NMDA antagonist; Postural Balance - drug effects; Rapid tolerance; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - drug effects; Toxicology; NMDA antagonist; Rapid tolerance; D-Cycloserine; Ethanol; (+)MK-801; Intraperitoneal administration; Rat; Psychotropic; Rodentia; Tolerance; Glutamate receptor; Vertebrata; Mammalia; Animal; Glycine receptor; Excitatory aminoacid; Mechanism of action; NMDA receptor
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/0091-3057(93)90152-J

We recently reported that the noncompetitive NMDA antagonists, (+)MK-801 and ketamine, block the development of rapid tolerance to ethanol. In the present article, we show that D-cycloserine (CS), an agonist at the glycine site of the NMDA receptor that enhances learning and memory, also enhances the development of rapid tolerance to ethanol. Rats were pretreated on day 1 with saline or CS, followed 30 min later by ethanol (2.3 g/kg, IP) or saline. At the end of motor impairment testing on the tilt-plane apparatus, a second injection of CS (3 mg/kg, IP, each time) or saline was given, followed 30 min later by ethanol or saline. Ethanol pretreatment alone (at this dose) did not result in rapid tolerance to ethanol on day 2. However, the group pretreated with CS and ethanol on day 1 showed significant tolerance on day 2 compared to other groups. Pretreatment with CS on day 1 did not affect the motor impairment response to the first exposure to ethanol whether this was on day 1 or day 2. In another experiment, administration of (+)MK-801 (0.25 mg/kg, IP) prior to CS abolished the rapid tolerance enhancement by CS. These findings are further evidence that the NMDA system, which requires activation by the glycine receptor, plays a major role in the development of at least some forms of ethanol tolerance.