The benzodiazepine recognition site inverse agonists Ro 15-4513 and FG 7142 both antagonize the EEG effects of ethanol in the rat.
The aim of the present study was to compare the ability of Ro 15-4513 and FG 7142, two inverse agonists for benzodiazepine recognition sites, to antagonize the EEG effects of ethanol in freely moving rats. Ethanol (2.5 g/kg, p.o.) induced sedation and ataxia associated with a progressive suppression of the fast cortical activities and an enhancement of low frequencies in both cortical and hippocampal tracings. In contrast, Ro 15-4513 (2 mg/kg, i.p.) and FG 7142 (10 mg/kg, i.p.) both caused a state of alertness associated with desynchronized cortical activity and theta hippocampal rhythm as well as spiking activity which was predominantly observed in the cortical tracings. When rats were treated with FG 7142 or RO 15-4513 either before or after ethanol, a reciprocal antagonism of the behavioral and EEG effects of ethanol and of the partial inverse agonists was observed. These data support the view that the anti-ethanol effects of Ro 15-4513 may be related to its partial inverse agonist properties.
Marrosu
F
F
Department of Experimental Biology, University of Cagliari, Italy.
Mereu
G
G
Giorgi
O
O
Corda
M G
MG
D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology; D001386:Azides / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002243:Carbolines / Q000494:pharmacology*; D004569:Electroencephalography; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D012016:Reference Values
D001067:Appetite Depressants; D001386:Azides; D002243:Carbolines; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D000431:Ethanol; C035874:FG 7142; C042957:Ro 15-4513