Post-training down-regulation of memory consolidation by a GABA-A mechanism in the amygdala modulated by endogenous benzodiazepines.

In rats, amygdala benzodiazepine-like immunoreactivity decreases by 29% immediately after the animals step down from the platform of an inhibitory avoidance apparatus and decreases by a further 45% immediately after they receive a training footshock. The decrease is attributable to a release of diazepam or diazepam-like molecules. The immediate post-training intraamygdala injection of the central benzodiazepine antagonist flumazenil (10 nmole/amygdala) causes memory facilitation, and that of the GABA-A agonist muscimol (0.005 to 0.5 nmole) causes retrograde amnesia. Pretraining ip flumazenil administration (2.0 and 5.0 mg/kg) attenuates the effect of post-training muscimol by a factor of at least 100. The higher dose of pretraining flumazenil also causes memory facilitation. The data suggest that post-training consolidation is down-regulated by a GABA-A mechanism in the amygdala modulated by endogenous benzodiazepines released during training and at the time of consolidation.