The effect of combined administration of ethanol and gabapentin on rabbit electroencephalographic activity.
The central effect of ethanol is mainly connected with the effect on GABAergic, glutamatergic, serotonergic and opioid transmission. The mechanism of gabapentin effect suggests that it may alleviate the rewarding effect of ethanol, which may be used in the treatment of addiction. We decided to examine the interaction of ethanol with gabapentin by a pharmaco-electroencephalographic (EEG) method. The influence of gabapentin on the effect of ethanol on EEG of rabbits (midbrain reticular formation, hippocampus, frontal cortex) was tested. Gabapentin was administered at a single dose (25 and 100 mg/kg orally) or repeatedly twice a day at a total dose of 25 mg/kg for 14 days. Ethanol was injected at a dose of 0.8 g/kg 60 min. after gabapentin treatment. Ethanol caused an increase in the slow frequencies (0.5-4 Hz) in the recording, as well as a marked decrease of the fastest frequencies (13-30 and 30-45 Hz). Gabapentin lead to changes in rabbit EEG recording suggesting an depressant effect on the CNS (increase of slow and decrease of fast frequencies). The effects were less pronounced after repeated doses, which may indicate adaptative changes in the receptors. Gabapentin administered both in a single dose and for 7 days markedly enhanced the effect of ethanol on EEG recordings in rabbits. Repeated doses of gabapentin decrease the sensitivity of the hippocampus to the effect of ethanol.
Pietrzak
Bogusława
B
Department of Pharmacodynamics, Medical University of Łódź, Muszyńskiego 1, 90-151 Łódź, Poland. bpietrzak@pharm.am.lodz.pl
Czarnecka
Elzbieta
E
D000588:Amines / Q000633:toxicity*; D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002492:Central Nervous System Depressants / Q000633:toxicity*; D003509:Cyclohexanecarboxylic Acids / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004569:Electroencephalography / Q000187:drug effects*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D000077206:Gabapentin; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D011817:Rabbits; D005680:gamma-Aminobutyric Acid / Q000633:toxicity*
D000588:Amines; D000927:Anticonvulsants; D002492:Central Nervous System Depressants; D003509:Cyclohexanecarboxylic Acids; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin