Benzodiazepine-induced epileptiform activity in vitro.
Drug naive rat hippocampal slices were incubated in artificial cerebrospinal fluid (ACSF) containing 20 nM clonazepam, a concentration approximating those measured in the cerebrospinal fluid (CSF) of rats treated with high doses of clonazepam which resulted in behavioral hyperexcitability and convulsions upon withdrawal. In the slice, epileptiform activity began within 2 h of incubation in clonazepam. This activity was enhanced upon drug withdrawal. Measured intracellularly, the long-lasting post-spike train afterhyperpolarization was reduced in duration in drug-treated cells whereas just subthreshold antidromic or orthodromic IPSPs were not changed. As some of the hyperexcitability phenomena noted here were similar to those observed in slices taken from rats chronically administered with clonazepam, the technique of long-term in vitro exposure to substances which cause tolerance and dependence may be a useful model of drug withdrawal epilepsy.
Department of Neurology, Stanford University School of Medicine, CA 94305.
M F
MF
Davies
S E
SE
Sasaki
P L
PL
Carlen
D000818:Animals; D002998:Clonazepam / Q000633:toxicity*; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D002998:Clonazepam