ETHANOL ENHANCES MUSCARINIC CHOLINERGIC NEUROTRANSMISSION IN RAT HIPPOCAMPUS IN-VITRO

Previous studies from our laboratory showed that ethanol enhances musc arinic excitatory responses in rat hippocampal neurons in vivo and, li ke muscarinic agonists, reduces the M-current (I-M) in these neurons i n vitro. Therefore, we used extracellular and intracellular recording techniques in the hippocampal slice preparation to examine the mechani sms underlying this ethanol-muscarinic interaction. Surprisingly, supe rfusion or local application of low concentrations of acetylcholine (A Ch), carbachol (CCh) or muscarine reduced the amplitudes of CA1 field potentials evoked by stratum radiatum (SR) stimulation. This effect wa s blocked by 1 mu M atropine but was independent of the method of agon ist application, the site of application or the SR stimulus paradigm. In intracellular and extracellular single unit recordings, cholinergic depressions of field potentials were correlated with: (1) depolarizat ion of pyramidal neurons; (2) spike discharge increases; (3) reduction of amplitudes of postsynaptic potentials and (4) reduction of late af terhyperpolarizations (AHPs). Superfusion of low ethanol concentration s (11-22 mM) alone had little effect on SR-evoked field potentials but enhanced (by 10-90%) both the depressions of evoked field potentials and depolarizations elicited by the muscarinic agonists. Ethanol (22-4 4 mM) also enhanced both the amplitude and duration of the muscarinic slow excitatory postsynaptic potentials (sEPSPs) recorded intracellula rly in CA1 and CA3 neurons. This effect was enhanced by eserine and bl ocked by atropine, verifying involvement of muscarinic receptors. Thes e results suggest that: (1) caution be used in interpreting results of field potential studies regarding drug-induced excitability changes; and (2) ethanol in just-intoxicating concentrations enhances endogenou s muscarinic synaptic transmission as well as responses to exogenous m uscarinic agonists.