The role of serotonin(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(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.
O'Dell
L E
LE
Amethyst Technologies, Inc., 1435 North Hayden Road, Scottsdale, AZ, USA.
Kreifeldt
M J
MJ
George
F R
FR
Ritz
M C
MC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D018765:Dopamine Uptake Inhibitors; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D003042:Cocaine