SEIZURES DURING ETHANOL WITHDRAWAL ARE BLOCKED BY FOCAL MICROINJECTION OF EXCITANT AMINO-ACID ANTAGONISTS INTO THE INFERIOR COLLICULUS AND PONTINE RETICULAR-FORMATION

Physical dependence on ethanol can result in seizure susceptibility du ring ethanol withdrawal. In rats, generalized tonic-clonic seizures ar e precipitated by auditory stimulation during the ethanol withdrawal s yndrome. Excitant amino acids (EAAs) are implicated as neurotransmitte rs in the inferior colliculus and the brain stem reticular formation, which play important roles in the neuronal network for genetic models of audiogenic seizures (AGSs). Ethanol blocks the actions of EAAs in v arious brain regions, including the inferior colliculus. In this study , dependence was produced by intragastric administration of ethanol fo r 4 days. During ethanol withdrawal, AGSs were blocked by systemic adm inistration of competitive or noncompetitive NMDA antagonists (+/-)-2- carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) or dizocilpine ( MK-801). Focal microinjections of NMDA or non-NMDA antagonists into th e inferior colliculus or the pontine reticular formation also inhibite d AGSs. MK-801 was the most potent anticonvulsant systemically. When i njected into the inferior collicutus, CPP had a more potent anticonvul sant effect than either MK-801 or the non-NMDA antagonist 6-cyano-7-ni troquinoxaline-2,3-dione. The inferior colliculus was more sensitive t han the pontine reticular formation to the anticonvulsant effects of b oth competitive NMDA and non-NMDA antagonists. The results of the pres ent support the idea that continued ethanol administration may lead to development of supersensitivity to the action of EAAs in inferior col liculus and pontine reticular formation neurons. This may be a critica l mechanism subserving AGS susceptibility during ethanol withdrawal.