The Role of Serotonin sub(2) Receptors in Mediating Cocaine-Induced Convulsions

Previous research in our laboratory suggests that serotonin (5-HT) neurotransmission mediates the expression of cocaine-induced convulsions. The role of 5-HT in mediating this toxic effect of cocaine appears to be due to activation of 5-HT sub(2) receptors, because cocaine-induced convulsions are bl...

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Published in:Pharmacology, biochemistry and behavior biochemistry and behavior, 2000-04, Vol.65 (4), p.677-681
Main Authors: O'Dell, LE, Kreifeldt, MJ, George, FR, Ritz, M C
Format: Article
Language:English
Subjects:
cinanserin
ketanserin
pirenperone
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Summary:Previous research in our laboratory suggests that serotonin (5-HT) neurotransmission mediates the expression of cocaine-induced convulsions. The role of 5-HT in mediating this toxic effect of cocaine appears to be due to activation of 5-HT sub(2) receptors, because cocaine-induced convulsions are blocked by the 5-HT sub(2) antagonists cinanserin, ketanserin, and pirenperone. The present study utilized a number of compounds that display a high affinity for 5-HT sub(2) receptors to further examine the role of these sites in mediating this toxic effect of cocaine. Cocaine-induced convulsions were observed following pretreatment with various doses of the following 5-HT sub(2) antagonists: mianserin, metergoline, MDL 11939, and methiothepin. In addition, 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN 190) was tested to examine the influence of 5-HT sub(1) sites and the agonist compound 1-(3-triflurormethylphenyl)piperazine (TFMPP) was examined to further explore the role of 5-HT sub(1) and 5-HT sub(2) sites. Each 5-HT sub(2) antagonist attenuated cocaine-induced convulsions. Conversely, NAN 190 did not alter this toxic effect of cocaine. In addition, TFMPP significantly potentiated cocaine-induced convulsions. The results from this study support the hypothesis that 5-HT neurotransmission, acting primarily at 5-HT sub(2) receptors, plays an important role in mediating cocaine-induced convulsions.
ISSN:0091-3057