Lack of feedback inhibition on rat basolateral amygdala following stress or withdrawal from sedative-hypnotic drugs.
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 GABA(A) receptors by picrotoxin. However, IPSPs were clearly reduced in diazepam- or ethanol-withdrawn and in stressed rats. 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 three experimental models; these IPSCs were mediated by GABA(A) receptor activation and were blocked after suppression of glutamatergic transmission. In contrast, no IPSCs were observed in slices from diazepam- or ethanol-withdrawn or stressed animals, although the depolarizing pulse regularly evoked an AP in pyramidal neurons. It is concluded that, in withdrawn or stressed rats, GABAergic disinhibition occurs due to attenuation or suppression of feedback inhibition.
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Nora A
NA
Isoardi
Maria E
ME
Bertotto
Irene D
ID
Martijena
Victor A
VA
Molina
Hugo F
HF
Carrer
D000679:Amygdala / Q000503:physiopathology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000009:adverse effects; D003975:Diazepam / Q000009:adverse effects; D004558:Electric Stimulation; D004594:Electrophysiology; D000431:Ethanol / Q000009:adverse effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005246:Feedback / Q000502:physiology; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D008297:Male; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000503:physiopathology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D002492:Central Nervous System Depressants; D006993:Hypnotics and Sedatives; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D003975:Diazepam