Carbamazepine retards the development of cocaine-kindled seizures but not sensitization to cocaine-induced hyperactivity.
The effects of chronic carbamazepine on cocaine-kindled seizures and behavioral sensitization were examined in this study. Rats were fed a diet containing carbamazepine or no drug and then repeatedly administered cocaine (40 and 50 mg/kg intraperitoneally [IP] [117.6 and 147.0 mumol/kg, respectively]). Carbamazepine markedly decreased the development of cocaine-kindled seizures and their associated lethality, but did not affect the development of sensitization of behavioral stereotypies. Carbamazepine consistently decreased the peak stereotypy ratings at the 40 mg/kg but not 50 mg/kg dose. In a 2-day sensitization paradigm chronic carbamazepine did not affect acute cocaine-induced hyperactivity (day 1; 40 mg/kg), nor did it affect sensitization to a low dose challenge of cocaine (day 2; 10 mg/kg [29.4 mumol/kg]). Sensitization of stereotypy and locomotor activity are thought to be related to the psychomotor stimulant properties of cocaine, while seizures may be associated with cocaine's local anesthetic effects. Our data suggest that carbamazepine is inhibiting mechanisms associated with local anesthetic kindling and only minimally affecting the psychomotor stimulant effects of cocaine.
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892.
S R
SR
Weiss
R M
RM
Post
M
M
Costello
D J
DJ
Nutt
S
S
Tandeciarz
D000818:Animals; D002220:Carbamazepine / Q000494:pharmacology* / Q000627:therapeutic use; D003042:Cocaine / Q000494:pharmacology*; D006948:Hyperkinesis / Q000139:chemically induced / Q000503:physiopathology; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011336:Probability; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D013239:Stereotyped Behavior / Q000187:drug effects*
D002220:Carbamazepine; D003042:Cocaine