The role of serotonin(2) receptors in mediating cocaine-induced convulsions.

Abstract

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(2) receptors, because cocaine-induced convulsions are blocked by the 5-HT(2) antagonists cinanserin, ketanserin, and pirenperone. The present study utilized a number of compounds that display a high affinity for 5-HT(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(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(1) sites and the agonist compound 1-(3-triflurormethylphenyl)piperazine (TFMPP) was examined to further explore the role of 5-HT(1) and 5-HT(2) sites. Each 5-HT(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(2) receptors, plays an important role in mediating cocaine-induced convulsions.

• Authors: L E O'Dell, M J Kreifeldt, F R George, M C Ritz
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 65 Issue 4 Pg. 677-81 (Apr 2000) ISSN: 0091-3057 [Print] United States
• PMID: 10764922 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Dopamine Uptake Inhibitors
• Receptor, Serotonin, 5-HT2C
• Receptors, Serotonin
• Receptors, Serotonin, 5-HT1
• Serotonin Antagonists
• Serotonin Receptor Agonists
• Cocaine

Topics

• Animals
• Behavior, Animal (drug effects)
• Cocaine (antagonists & inhibitors, toxicity)
• Dopamine Uptake Inhibitors (antagonists & inhibitors, toxicity)
• Dose-Response Relationship, Drug
• Male
• Mice
• Mice, Inbred C57BL
• Receptor, Serotonin, 5-HT2C
• Receptors, Serotonin (drug effects, physiology)
• Receptors, Serotonin, 5-HT1
• Seizures (chemically induced, physiopathology)
• Serotonin Antagonists (pharmacology)
• Serotonin Receptor Agonists (pharmacology)