Prior stress promotes the generalization of contextual fear memories: Involvement of the gabaergic signaling within the basolateral amygdala complex

OTAMENDI, A.; BENDER, C.L.; MOLINA, V.A.; BENDER, C.L.; MOLINA, V.A.; CALFA, G.D.; CALFA, G.D.; OTAMENDI, A.

PROGRESS OF NEUROPSYCHOPHARMACOLOGY AND BIOLOGICAL PSYCHIATRY

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2018 vol. 83 p. 18 - 26

0278-5846

Fear generalization occurs when a response, previously acquired with a threatening stimulus, is transferred to asimilar one. However, it could be maladaptive when stimuli that do not represent a real threat are appraised asdangerous, which is a hallmark of several anxiety disorders. Stress exposure is a major risk factor for the occurrenceof anxiety disorders and it is well established that it influences different phases of fear memory;nevertheless, its impact on the generalization of contextual fear memories has been less studied. In the presentwork, we have characterized the impact of acute restraint stress prior to contextual fear conditioning on thegeneralization of this fear memory, and the role of the GABAergic signaling within the basolateral amygdalacomplex (BLA) on the stress modulatory effects. We have found that a single stress exposure promoted thegeneralization of this memory trace to a different context that was well discriminated in unstressed conditionedanimals. Moreover, this effect was dependent on the formation of a contextual associative memory and on thetesting order (i.e., conditioning context first vs generalization context first). Furthermore, we observed thatincreasing GABA-A signaling by intra-BLA midazolam administration prior to the stressful session exposureprevented the generalization of fear memory, whereas intra-BLA administration of the GABA-A antagonist(Bicuculline), prior to fear conditioning, induced the generalization of fear memory in unstressed rats. Weconcluded that stress exposure, prior to contextual fear conditioning, promotes the generalization of fearmemory and that the GABAergic transmission within the BLA has a critical role in this phenomenon.