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 followi ng studies sought to identify potential sources of this long-term chan ge 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 postwithdrawal. The magnitude of this change was related to the number of withdrawals (6 w ithdrawals, -2.0 +/- 0.3 Hz; 10 withdrawals, -3.2 +/- 1.2 Hz). Thus, m ultiple ethanol withdrawals increased seizure sensitivity within the i nferior collicular cortex. On the following day in the same animals, c hanges 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 curre nt within the inferior collicular cortex. Seizure sensitivity to colli cular N-methyl-D-aspartic acid (NMDA) microinjection was decreased aft er 6 ethanol withdrawals, and increased after 10 withdrawals, but cont rol liquid diet animals exhibited similar responses to collicular NMDA microinjection. Therefore, multiple withdrawals from ethanol alters t he seizure sensitivity within the inferior collicular cortex. One poss ible contribution to this change is a local decrease in GABA inhibitor y function.