Previous stress facilitates fear memory, attenuates GABAergic inhibition, and increases synaptic plasticity in the rat basolateral amygdala.
In experiments designed to investigate the relationship between stress and the acquisition of new fear memories, it was found that previous exposure to a restraint session increased fear conditioning in a contextual fear paradigm. Moreover, the infusion of bicuculline, a competitive antagonist of GABAA receptors, into the basolateral amygdala complex (BLA), but not into the central amygdaloid nucleus, induced the same behavioral effect. Pretreatment with midazolam (MDZ), a positive modulator of GABAA sites, prevented the facilitating influence on fear memory of both stress and GABAA receptor blockade in the BLA. These data suggest that facilitation of fear conditioning could be causally related to increased neuronal excitability attributable to depressed GABAergic inhibition in the BLA. To test this hypothesis, evoked potentials were studied in brain slices from stressed animals. Potentials evoked in the BLA by single stimuli applied to the external capsule showed multispike responses, suggestive of GABAergic disinhibition. These multiple responses were no longer evident after the slices were perfused with diazepam or if the stressed animals were pretreated with MDZ. In slices from stressed rats, paired-pulse inhibition (GABA dependent) was suppressed. Also, in stressed animals, long-term potentiation (LTP) was induced with a single train of high-frequency stimulation, which did not induce LTP in control rats. Moreover, MDZ pretreatment prevented the facilitating influence of stress on LTP induction. All of these findings support the hypothesis that previous stress attenuates inhibitory GABAergic control in the BLA, leading to neuronal hyperexcitability and increased plasticity that facilitates fear learning.
Rodríguez Manzanares
Pablo A
PA
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, 5016 Córdoba, Argentina.
Isoardi
Nora A
NA
Carrer
Hugo F
HF
Molina
Víctor A
VA
D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D005239:Fear / Q000187:drug effects / Q000502:physiology* / Q000523:psychology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008874:Midazolam / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000503:physiopathology* / Q000523:psychology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D005680:gamma-Aminobutyric Acid; D008874:Midazolam