Presentation of a tonal cue that previously had been associated with a fearful experience (footshock) produces alterations in arousal and sleep that occur after the fearful cue is no longer presented. To begin investigating neurochemical mechanisms that may underlie the effects of fearful cue presentation, we measured release of [(3)H]-norepinephrine ([(3)H]-NE]) and [(14)C]-gamma-amino-butyric acid ([(14)C]-GABA) from brain regions known to regulate arousal states and REM sleep. Depolarization-evoked release of [(3)H]-NE from amygdalar slices of mice, which were trained to recognize a tone as a fearful cue, was suppressed at 2-3 h after exposure of animals to the fearful cue, but recovered after 4-5 h. Interestingly, depolarization-evoked release of [(14)C]-GABA was significantly increased in the amygdala, and also showed a tendency for enhancement in the hippocampus, NPO, and DRN at 2-3 h after cue presentation. The changes in [(14)C]-GABA release were also transient; 4-5 h after cue presentation no significant differences were detected between samples derived from experimental groups which experienced fearful or neutral cues. The similar time course of fearful cue-induced changes in neurotransmitter release and changes in arousal and REM sleep suggests that alterations in amygdalar neurotransmission may be involved in the changes in arousal and sleep that occur after fear.