Many of the effects of acute alcohol exposure and long-term abuse are correlated with changes in hippocampal function, or can be mimicked by experimental manipulations of the hippocampus. Hippocampal cholinoceptive neurons and their cholinergic afferents may be particularly responsive to ethanol, although the specific involvement of these neurons in ethanol-induced changes in behavior and in neuronal morphology have yet to be determined. The research proposed here will determine the effects of acute, intrahippocampal ethanol application upon the activity of hippocampal pyramidal cells and will examine the development and dissipation of tolerance to these effects following chronic ethanol treatment and withdrawal in laboratory rats. In order to further investigate the effects of ethanol on the function of these neurons, the proposed studies will examine the effects of acute and chronic ethanol on the responsiveness of hippocampal neurons to locally-applied neurotransmitters and to stimulation of their cholinergic, septal afferents. The proposed experiments will characterize the effects of medial septal stimulation on single-cell activity within the hippocampal CA3 field. To verify the cholinergic nature of this stimulation effect, animals will be treated with M, or M2 muscarinic, cholinergic receptor antagonists to block cholinergic activity. The effects of these treatments on stimulated hippocampal activity will be determined. Other studies will examine the effects of acute ethanol (0, 0.5, 1.0, or 1.5 g/kg, i.p.) on this activity, and the effects of varying length of chronic ethanol exposure and time of testing post-withdrawal. These studies will provide information about the basic mechanisms of ethanol action on a defined cell population in the central nervous system, and will permit an examination of the development and dissipation of changes in the functioning of this population with chronic ethanol exposure and withdrawal. The information obtained may be of importance in understanding and developing treatments for the effects of acute and chronic ethanol on behavior, cognitive functioning, and neuronal morphology.
