Time-related antiepileptic effects of the synthetic glucocorticoid dexamethasone in rat hippocampal slices.
The in vitro antiepileptic activity of the synthetic glucocorticoid dexamethasone (DEX) was tested in rat hippocampal slices on the CA1 epileptiform activity induced by sodium penicillin (PEN). Slice perfusion with 1 mM PEN produced within 60 min the development of a CA1 epileptiform bursting made up of an increase of the primary CA1 population spike followed by the appearance of secondary epileptiform population spikes. Slice perfusion with 100 microM DEX together with PEN (1 mM) partially prevented but did not block the expression of the CA1 epileptiform bursting as evidenced by a significant (P < 0.05) reduction of the duration of the bursting due to the epileptogenic agent. Slice perfusion with 50 microM DEX together with PEN (1 mM) failed to prevent or block the expression of the CA1 penicillin-induced epileptiform bursting. A 60 min slice pretreatment with 50-100 microM DEX followed by a slice perfusion with 50-100 microM DEX together with PEN (1 mM) prevented the expression of the CA1 epileptiform bursting. Cycloheximide (1 microM), a protein synthesis inhibitor, perfused together with DEX reverted the inhibitory effects of dexamethasone on the expression of the penicillin-induced CA1 epileptiform bursting. The results indicate that the synthetic glucocorticoid DEX presents concentration- and time-related in vitro antiepileptic effects. In addition, the data suggest that this inhibitory effect occurs via a protein synthesis-dependent mechanism.
Sagratella
S
S
Laboratorio di Farmacologia, Istituto Superiore di Sanità, Roma, Italy.
Di Giannuario
A
A
Pieretti
S
S
Loizzo
A
A
Domenici
M R
MR
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000493:pharmacokinetics / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010406:Penicillins / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D010406:Penicillins; D003907:Dexamethasone; D003513:Cycloheximide