Efforts at public education regarding the unique risks of alcohol drinking by minors are hampered by a striking lack of information about the effects of this drug on the postnatal developing brain. Our recent findings indicate that NMDA receptor-mediated synaptic activity and synaptic plasticity in the immature hippocampus is markedly more sensitive to ethanol than it is in the mature hippocampus (Swartzwelder et al., 1995a, b). Our recent preliminary data confirm this difference in potency using whole cell recordings from hippocampal neurons (see Section 9,C below). Most importantly, we now have preliminary data from behavioral experiments which show that mild to moderate doses of ethanol attenuate the acquisition of spatial memory more potently in immature rats than in adults (See Section 9,C below.). If these initial findings are confirmed by the studies we propose, they will have immense public educational value relative to the risks of children and adolescents who drink. We propose three Specific Aims to address these questions in detail. The experiments under Specific Aim 1 will utilize whole cell recording techniques to assess the effects of ethanol on NMDA receptor-mediated EPSCs in pyramidal cells in area CA1 of hippocampal slices taken from juvenile, adolescent, and adult rats. We will characterize the effects of a range of ethanol concentrations on the amplitude and kinetics of EPSCs. In addition, we will conduct experiments in the presence of a number of extra- and intracellular media to begin to determine the mechanisms underlying the developmental differences in ethanol sensitivity.
Specific Aim 2 will determine the effects of a range of ethanol concentrations on the induction of long-term potentiation (LTP) in hippocampal area CA1 from rats of the ages described above. If ethanol is more potent against NMDA mediated neurotransmission and synaptic plasticity in the immature hippocampus, then it may also more potently disrupt the formation of spatial memory. Our preliminary data support this hypothesis, and Specific Aim 3 will test it in detail.
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