Abnormalities in the central cholinergic transmitter system of the genetically epilepsy-prone rat.

Seizure-experienced Genetically Epilepsy-prone Rats (GEPRs) have increased acetylcholine content and choline acetyltransferase activity in the thalamus and striatum. These cholinergic differences are accompanied by a slight but statistically significant reduction in acetylcholinesterase activity in the midbrain. In addition, no abnormalities were found in the numbers of specific 3H-QNB binding sites in the striatum, hippocampus, inferior colliculi or cortex. Other work has shown no difference in muscarinic receptor function as measured by carbachol-stimulated inositol-1-phosphate formation. These data suggest a possible presynaptic defect in the striatal and thalamic cholinergic system which may play some role in the seizure-prone state of the GEPR. However, caution must be used in interpreting these cholinergic derangements since more recent findings show no differences in thalamic acetylcholine content in seizure-naive GEPRs. Thus, the original cholinergic abnormalities detected in the seizure-experienced GEPR may be an enduring response to seizure activity.