Ethanol potentiates gamma-aminobutyric acid-mediated inhibition in the inferior colliculus: evidence for local ethanol/gamma-aminobutyric acid interactions.
The effect of ethanol on gamma-aminobutyric acid (GABA)-mediated inhibition of neurons of the inferior collicular cortex (IC) was investigated. Systemic administration of 0.5 g/kg ethanol, but not 0.25 g/kg ethanol, potentiated the inhibitory effect of GABA on IC neuronal activity. As with systemic administration of ethanol, local application of two concentrations of ethanol potentiated, in a dose-dependent and concentration-dependent manner, GABA-mediated inhibition of IC activity. When utilizing the lower ethanol concentration (270 mM), increasing ethanol ejection currents produced a correspondingly greater amount of augmentation of GABA inhibition without concomitant changes in spontaneous neural activity. At the highest ejection current tested (90 nA), ethanol doubled the inhibitory effects of GABA on IC neuronal activity. Local application of a higher concentration of ethanol (2.7 M) also potentiated GABA-mediated inhibition, with greater ejection currents producing greater potentiation of GABA-inhibition. Compared to the lower ethanol concentration, the higher ethanol concentration required lower ejection currents to produce comparable amounts of potentiation of GABA inhibition. These findings demonstrate that ethanol potentiates GABA inhibition of IC activity via a local action. In contrast to the effects of ethanol on GABA inhibition, locally applied ethanol failed to potentiate the inhibition by glycine of IC activity, indicating that ethanol does not indiscriminately potentiate all types of inhibition of IC neural activity. Additionally, locally applied ethanol failed to potentiate inhibition by GABA in the lateral septum, indicating that ethanol/GABA interactions are site specific. These findings indicate that ethanol specifically potentiates GABA-mediated inhibition of neural activity, and that this action occurs via a local action at specific sites in brain.
Simson
P E
PE
Department of Psychiatry, University of North Carolina, School of Medicine, Chapel Hill.
Criswell
H E
HE
Breese
G R
GR
D000818:Animals; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D005998:Glycine / Q000494:pharmacology; D007245:Inferior Colliculi / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007478:Iontophoresis; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D005998:Glycine