Lack of feed-back inhibition on rat basolateral amygdala following stress or withdrawal from sedative-hypnotic drugs

NORA A. ISOARDI, MARIA E. BERTOTTO, IRENE D. MARTIJENA, VICTOR A. MOLINA AND HUGO F. CARRER.

EUROPEAN JOURNAL OF NEUROSCIENCE

Blackwell

Lugar: Londres; Año: 2007 vol. 26 p. 1036 - 1044

0953-816X

Previous research has demonstrated that suppression of inhibition in  projection neurons of the basolateral complex of the amygdala (BLA) represents an essential  mechanism underlying  the emergence of negative emotional responses, including exaggerated fear and anxiety. The present work evaluates inhibitory postsynaptic potentials (IPSPs)  in pyramidal projection neurons of the BLA, in rats subjected to either diazepam or ethanol withdrawal, or uncontrollable stress. These are experimental paradigms conducive to a negative emotional state. In slices containing the BLA, IPSPs were studied using whole cell patch-clamp. In control animals, a small IPSP was evoked by sub-threshold stimulation of the external capsule. When an action potential (AP) was evoked by supra-threshold stimuli, IPSPs were considerably larger; these IPSPs were sensitive to blockade of GABAA receptors by picrotoxin. On the other hand, in diazepam or ethanol withdrawn and in stressed rats IPSPs were clearly reduced. Firing of an AP by a depolarizing pulse applied through the patch pipette consistently evoked an inhibitory postsynaptic current (IPSC) in the pyramidal neurons of control animals from all 3 experimental models; these IPSCs were mediated by GABAA receptor activation and were blocked after suppression of glutamatergic transmission. In contrast, in slices from diazepam or ethanol withdrawn or stressed animals, no IPSCs were observed, although the depolarizing pulse regularly evoked an AP in pyramidal neurons. It is concluded that in withdrawn or stressed rats GABAergic disinhibition occurs due to attenuation or suppression of feedback inhibition.