Interaction between N-methyl-D-aspartate (NMDA) and serotonin (5-HT) on ethanol tolerance.
Earlier work from this laboratory had shown that 5-HT is involved in the development of tolerance to ethanol, and that enhancement of 5-HT levels by L-tryptophan accelerated tolerance development. To explore the possibility that NMDA receptors are involved in the 5-HT effect on tolerance, we examined the effect of a noncompetitive N-methyl-D-aspartate (NMDA) antagonist [(+)MK-801] on the ability of L-tryptophan to enhance tolerance to the effect of ethanol on tilt-plane test performance by the rat. L-Tryptophan treatment resulted in the development of rapid tolerance to a dose of ethanol that failed to produce such tolerance by itself. However, prior administration of (+)MK-801 blocked the L-tryptophan effect on rapid tolerance development, in a dose-dependent manner. These results suggest that NMDA receptors are involved in the 5-HT enhancement of ethanol tolerance.
Department of Pharmacology, University of Toronto, Canada.
J M
JM
Khanna
H
H
Kalant
A
A
Chau
G
G
Shah
G S
GS
Morato
D000704:Analysis of Variance; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004361:Drug Tolerance; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013997:Time Factors; D014364:Tryptophan / Q000494:pharmacology
D012702:Serotonin Antagonists; D012701:Serotonin; D000431:Ethanol; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D014364:Tryptophan