EFFECTS OF CHRONIC ETHANOL ON CHOLINERGIC ACTIONS IN RAT HIPPOCAMPUS - ELECTROPHYSIOLOGICAL STUDIES ACID QUANTIFICATION OF M(1)-M(5) MUSCARINIC RECEPTOR SUBTYPES

The effects of chronic ethanol treatment (CET) on cholinergic modulati on of CA1 evoked field potentials and recurrent inhibition were invest igated in rat hippocampal slices. Densities of muscarinic receptor sub types were quantified in remaining hippocampal tissue by immunoprecipi tation. Iontophoretic application of ACh in stratum pyramidale results in facilitation of single evoked population spikes; application in st ratum radiatum results in depression of field EPSPs. CET decreased cho linergic facilitation of population spikes, while cholinergic inhibiti on of field EPSPs remained unaffected. Integrity of feedback (recurren t) inhibitory circuitry was evaluated by paired-pulse stimulation. As previously demonstrated, recurrent inhibition was significantly reduce d after CET; cholinergic disinhibition was also significantly reduced. Thus, CET appears to disrupt a subset of cholinergic effector systems within hippocampal neurons. The reductions in cholinergic function pr oduced by CET does not appear to be due to receptor loss, since muscar inic receptor subtype densities were not found to be significantly alt ered in this tissue. These results support the hypothesis that muscari nic receptor function is impaired in CA1 pyramidal cells through a dis ruption of intracellular signal transduction mechanisms. While it is u nclear whether cholinergic function is reduced in interneurons directl y, these results suggest that modulation of neuronal firing in the hip pocampus is markedly altered following CET due to impairment of both c holinergic and GABAergic systems.