EXAGERATED EMOTIONAL RESPONSES FOLLOWING WITHDRAWAL FROM HYPNOTIC-SEDATIVE DRUGS OR STRESS ARE ASSOCIATED WITH THE LACK OF FEED-BACK INHIBITION ON RAT BASOLATERAL AMYGDALA. Isoardi, N.A.; Rodriguez Manzanares, P.A.; Bertotto, M.E.1, Martijena, I.D.1; Carrer, H.F.2 and Molina, V.A1.1. Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba. 2 Instituto de Investigación Médica M. y M. Ferreira. INIMEC-CONICET. Córdoba, ARGENTINA. In this report we demonstrated that discontinuation from chronic ethanol (ETOH) and from diazepam (DZM) administration or previous exposure to an uncontrollable stressor facilitated the formation of a new fear memory. The infusion of bicuculline into the basolateral amygdala complex (BLA) induced the same behavioral effect. Using extracelullar recording methods, we demonstrated that withdrawn or stressed animals show increased neuronal excitability and facilitated LTP in the BLA. Pretreatment with midazolam prevented both the facilitating influence of stress on fear memory and synaptic excitability in the BLA. Inhibitory postsynaptic potentials (IPSPs), we studied in pyramidal neurons from BLA, using whole cell patch-clamp. In control animals, a small picrotoxin-sensitive IPSP was evoked by sub threshold stimulation of EC. When an action potential (AP) was evoked by supra threshold stimuli, the IPSPs were considerably larger. On the other hand, in DZM or ETOH withdrawn and in stressed rats IPSPs were significantly reduced. Firing of an AP by a depolarizing pulse applied through the patch pipitte consistently evoked a glutamatergic antagonists-sensitive inhibitory postsynaptic current (IPSCs) of control animals. In contrast, in slices from BZD or ETOHO withdrawn or stressed animals, IPSCs were greatly decreased. It is concluded that a history of severe stress or withdrawal to hypotic-sedative drugs results in the suppression of feed-back inhibition in BLA projection neurons, which represents an essential mechanism underlying the emergence of a negative emotional state, including exaggerated fear and anxiety.
