LOCALIZATION IN THE AMYGDALA OF THE AMNESTIC ACTION OF DIAZEPAM ON EMOTIONAL MEMORY

It is well known that systemically administered benzodiazepines (BZDs) induce anterograde amnesia in a variety of learning tasks. BZs effects are mediated through the GABA(A) complex by enhancing GABA-induced synaptic inhibition. As the GABAergic system in the amygdaloid complex (AC) is a site of action for the anxiolytic effects of BZs, such findings suggest that BZs may also influence memory through the amygdala. The present report summarizes a recent serie of experiments designed to examine this implication. In a first experiment rats received either sham or bilateral AC lesion using N-methyl-D-aspartic acid (NMDA). One week later, animals were trained on an inhibitory avoidance task and tested 48 h later. Diazepam (DZP; 1.0 and 2.0 mg/kg, i.p.) or vehicle was injected 30 min prior to acquisition. The results demonstrate that DZP-induced retention deficits was blocked in rats with AC lesions. In a second experiment, in an attempt to localize the site of BZDs amnestic action in the AC, we tested the effects of DZP in rats with bilateral ibotenic acid-induced lesions of central (CE), lateral (LAT) or basolateral (BL) amygdala nuclei. The results shown that retention was impaired in animals with CE and LAT lesions but not in animals with BL lesions. In a third experiment we tested the effects of DZP microinjections in different nuclei of the AC on retention performance of rats trained in an avoidance task. The results demonstrate that DZP microinjection prior training in the BL/LAT, but not CE nuclei produce anterograde amnesia. Taken together, these findings strongly suggest that the amnestic effects of DZP are mediate, at least in part, through influences involving the AC, in particular the BL amygdala nucleus. In addition, in a further study, some of us developed a new experimental model for measuring simultaneously drug effects on anxiety and memory: the elevated T maze. In rats placed in this T maze, consisting of an enclosed arm at a right angle with open arms elevated 50 cm above the ground, DZP (2 and 4 mg/kg, i.p.) abolished the delay of withdrawal from the enclosed arm towards the open arms in tests immediately after the training as well as 72 h later, suggesting both an anxiolytic and an amnestic effect in this inhibitory avoidance paradigm. In contrast, in the same subject, DZP did not affect the latency of withdrawal from one of the open arms towards the closed arm. Moreover, on the 72 h later test, the latency of this escape response decreased in all groups, indicating that memory of this task was resistant to DZP. These results further support the view that the anxiolytic and the amnestic effects of BZs are closely related.