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The acoustic startle reflex is a co-ordinated contraction of the skeletal musculature in response to a sudden, intense sound. One form of startle plasticity, “prepulse inhibition”, is the normal suppression of the startle reflex when the intense startling stimulus is immediately preceded by a weak pre-stimulus. Prepulse inhibition is utilized as an operational measure of sensorimotor gating, and is significantly impaired in several neuropsychiatric disorders that are characterized by symptoms associated with central inhibitory deficits. In rats, prepulse inhibition is disrupted by central dopamine activation or by manipulations of limbic cortical structures including the prefrontal cortex and hippocampus. In the present study, we assessed prepulse inhibition in rats after surgical and pharmacologic manipulations of the basolateral amygdala. Quinolinic acid lesions of the basolateral amygdala significantly reduced prepulse inhibition without significantly changing startle amplitude. These lesions also blocked fear-potentiated startle, which is known to be regulated by the basolateral amygdala. The prepulse inhibition-disruptive effects of basolateral amygdala lesions were not reversed by systemic injection of the dopamine antagonist haloperidol at doses that totally restored prepulse inhibition in apomorphine-treated rats. In other studies, intra-amygdala infusion of the competitive N-methyl-d-aspartate antagonist dl-2-amino-5-phosphonovaleric acid (0, 0.15, 1.5, 4.5μg) dose-dependently reduced prepulse inhibition.

Despite considerable evidence that ethanol can enhance chloride flux through the gamma-aminobutyric acid type A (GABA/A/) receptor-channel complex in several central neuron types, the effect of ethanol on hippocampal GABAergic systems is still controversial. Therefore, we have reevaluated this interaction in hippocampal pyramidal neurons subjected to local monosynaptic activation combined with pharmacological isolation of the various components of excitatory and inhibitory synaptic potentials, using intracellular current- and voltage-clamp recording methods in the hippocampal slice. In accord with our previous findings, we found that ethanol had little effect on compound inhibitory postsynaptic potentials/currents (IPSP/Cs) containing both GABA/A/ and GABA/B/ components. However, after selective pharmacological blockade of the GABA/B/ component of the IPSP (GABA/B/-IPSP/C) by CGP-35348, low concentrations of ethanol (22-66 mM) markedly enhanced the peak amplitude, and especially the area, of the GABA/A/ component (GABA/A/-IPSP/C) in most CA1 pyramidal neurons. Ethanol had no significant effect on the peak amplitude or area of the pharmacologically isolated GABA/B/-inhibitory postsynaptic current (IPSC). These results provide new data showing that activation of GABAB receptors can obscure ethanol enhancement of GABA/A/ receptor function in hippocampus and suggest that similar methods of pharmacological isolation might be applied to other brain regions showing negative or mixed ethanol-GABA interactions.