Serotonin(2C) receptors appear to mediate genetic sensitivity to cocaine-induced convulsions.
BACKGROUND
C57BL/6ByJ (6ByJ) and C57BL/6J (6J) mice differ in their sensitivity to cocaine-induced convulsions, with CD(50) values being 100 and 70 mg/kg, respectively. This genetic sensitivity to cocaine-induced convulsions is probably related to 5-HT(2) receptors, since the density of these sites and the concentration of 5-HT(2) antagonists required to block cocaine-induced convulsions is lower in 6J mice relative to 6ByJ mice.


OBJECTIVE
Although 5-HT(2) receptors appear to play a role in mediating genetic sensitivity to cocaine-induced convulsions, the role of 5-HT(2) receptor subtypes in this effect of cocaine has not been examined.


METHODS
The present study compared the effects of the preferential 5-HT(2C) agonists m-chlorophenylpiperazine (mCPP) and 6-chloro-2-(1-piperazinyl)pyrazine (MK212) on cocaine-induced convulsions in 6ByJ and 6J mice. General activity was also measured following pretreatment with mCPP and MK212.


RESULTS
Both mCPP and MK212 potentiated cocaine-induced convulsions and the effect of these agonists was more robust in 6ByJ mice relative to 6J mice.


CONCLUSIONS
The findings from this study support previous research suggesting that 5-HT(2) receptors play a role in mediating cocaine-induced convulsions, and extend previous research by suggesting that the 5-HT(2C) receptor subtype mediates cocaine-induced convulsions and genetic sensitivity to this toxic effect of cocaine.
O'Dell
L E
LE
Amethyst Technologies, Inc., 1435 North Hayden Road, Scottsdale, AZ 85257-3773, USA. lauraodell@aol.com
Kreifeldt
M J
MJ
George
F R
FR
Ritz
M C
MC
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced*; D013045:Species Specificity
D010879:Piperazines; D011719:Pyrazines; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D003042:Cocaine; C015068:1-(3-chlorophenyl)piperazine