Site-specific enhancement of gamma-aminobutyric acid-mediated inhibition of neural activity by ethanol in the rat medial septal area.
Because of uncertainty concerning the interaction of ethanol with gamma-aminobutyric acid (GABA) receptor-mediated events, the present work was designed to investigate the effect of ethanol on GABA transmission in the rat septal area using behavioral and electrophysiological techniques. Microinjection of the GABAA agonist muscimol into the medial septal area (MSA) enhanced, and bicuculline administration antagonized, ethanol-induced impairment of the aerial righting reflex. Microinjection of these drugs into the lateral septum (LSi) did not influence this measure of ethanol-induced sedation. Furthermore, intraseptal injections of muscimol or bicuculline in saline-treated rats had no effect on the aerial righting reflex. These data suggest that the MSA plays a critical modulatory role in the sedative actions of ethanol. To assess the effect of ethanol on muscimol responses in the MSA and LSi at the cellular level, GABA was applied by iontophoresis to rhythmically bursting neurons of the MSA and to cells in the LSi. The magnitude of the resultant inhibition by GABA on these cells was assessed before and after systemic administration of ethanol. Ethanol enhanced GABA-mediated inhibition of MSA neural activity, but did not alter GABA-mediated inhibition of cellular activity in the LSi. In contrast, the inhibition of cellular activity in the MSA, caused by a maximally effective concentration of the benzodiazepine flurazepam, was not altered by ethanol. Other work in the MSA demonstrated that electrical stimulation of the fimbria caused an inhibition of ongoing single unit activity that was reduced by concurrent application of bicuculline. The duration of this electrically elicited inhibition in the MSA was enhanced after ethanol injection and then recovered to base-line levels. In addition, ethanol (1.5 mg/kg) caused an enhancement of the inhibition induced by nipecotic acid, a GABA uptake inhibitor. These findings demonstrate that GABA-mediated neural inhibition is enhanced by ethanol in the MSA but not the LSi, indicating that the actions of ethanol on GABA-induced inhibition can be site specific. It is proposed that the cellular action of ethanol may depend upon a specific molecular composition of the GABA receptor complex which may vary at selected sites in the brain.
Givens
B S
BS
Neurobiology Curriculum, University of North Carolina, School of Medicine, Chapel Hill.
Breese
G R
GR
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D004347:Drug Interactions; D004594:Electrophysiology; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D009118:Muscimol; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline