Neonatal alcohol exposure impairs contextual fear conditioning in juvenile rats by disrupting cholinergic function.

The context preexposure facilitation effect (CPFE) is a variant of context fear conditioning in which context preexposure facilitates conditioning to immediate foot shock. Learning about context (preexposure), associating the context with shock (training), and expression of context fear (testing) occur in successive phases of the protocol. The CPFE develops postnatally, depends on hippocampal NMDA receptor function, and is highly sensitive to neonatal alcohol exposure during the weanling/juvenile period of development [15,16]. The present study examined some behavioral and pharmacological mechanisms through which neonatal alcohol impairs the CPFE in juvenile rats. We found that a 5-min context preexposure plus five 1-min preexposures greatly increases the levels of conditioned freezing compared to a single 5-min exposure or to five 1-min preexposures (Experiment 1). Increasing conditioned freezing with the multiple- exposure CPFE protocol does not alter the neonatal alcohol-induced deficit in the CPFE (Experiment 2). Finally, systemic administration of 0.01 mg/kg physostigmine prior to all three phases of the CPFE reverses this ethanol-induced deficit. These findings show that impairment of the CPFE by neonatal alcohol is not confined to behavioral protocols that produce low levels of conditioned freezing. They also support recent evidence that this impairment reflects a disruption of cholinergic function [18].