A potential contribution to ethanol withdrawal kindling: reduced GABA function in the inferior collicular cortex.
Because multiple withdrawals from chronic ethanol treatment facilitate the rate of kindling from the inferior collicular cortex, the following studies sought to identify potential sources of this long-term change in seizure sensitivity. When rats received 6 or 10 withdrawals from a 5-day ethanol liquid diet, a significant decrease was found in the threshold frequency for seizure genesis, 6-7 days post-withdrawal. The magnitude of this change was related to the number of withdrawals (6 withdrawals, -2.0 +/- 0.3 Hz; 10 withdrawals, -3.2 +/- 1.2 Hz). Thus, multiple ethanol withdrawals increased seizure sensitivity within the inferior collicular cortex. On the following day in the same animals, changes in inhibitory or excitatory function were evaluated within the inferior collicular cortex. We found a withdrawal-related increase in the effectiveness of bicuculline to reduce the seizure threshold current within the inferior collicular cortex. Seizure sensitivity to collicular N-methyl-D-aspartic acid (NMDA) microinjection was decreased after 6 ethanol withdrawals, and increased after 10 withdrawals, but control liquid diet animals exhibited similar responses to collicular NMDA microinjection. Therefore, multiple withdrawals from ethanol alters the seizure sensitivity within the inferior collicular cortex. One possible contribution to this change is a local decrease in GABA inhibitory function.
McCown
T J
TJ
Department of Psychiatry, University of North Carolina at Chapel Hill 27599-7250.
Breese
G R
GR
D000430:Alcohol Withdrawal Delirium / Q000503:physiopathology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D007245:Inferior Colliculi / Q000187:drug effects* / Q000503:physiopathology; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D001640:Bicuculline