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.
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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.)
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Chemical References |
- Dopamine Uptake Inhibitors
- Receptor, Serotonin, 5-HT2C
- Receptors, Serotonin
- Receptors, Serotonin, 5-HT1
- Serotonin Antagonists
- Serotonin Receptor Agonists
- Cocaine
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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)
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