Abstract
Intense or chronic stress can produce pathophysiological alterations in the systems involved in the stress response. The amygdala is a key component of the brain's neuronal network that processes and assigns emotional value to life's experiences, consolidates the memory of emotionally significant events, and organizes the behavioral response to these events. Clinical evidence indicates that certain stress-related affective disorders are associated with changes in the amygdala's excitability, implicating a possible dysfunction of the GABAergic system. An important modulator of the GABAergic synaptic transmission, and one that is also central to the stress response is norepinephrine (NE). In the present study, we examined the hypothesis that stress impairs the noradrenergic modulation of GABAergic transmission in the basolateral amygdala (BLA). In control rats, NE (10 microM) facilitated spontaneous, evoked, and miniature IPSCs in the presence of beta and alpha(2) adrenoceptor antagonists. The effects of NE were not blocked by alpha(1D) and alpha(1B) adrenoceptor antagonists, and were mimicked by the alpha(1A) agonist, A61603 (1 microM). In restrain/tail-shock stressed rats, NE or A61603 had no significant effects on GABAergic transmission. Thus, in the BLA, NE acting via presynaptic alpha(1A) adrenoceptors facilitates GABAergic inhibition, and this effect is severely impaired by stress. This is the first direct evidence of stress-induced impairment in the modulation of GABAergic synaptic transmission. The present findings provide an insight into possible mechanisms underlying the antiepileptogenic effects of NE in temporal lobe epilepsy, the hyperexcitability and hyper-responsiveness of the amygdala in certain stress-related affective disorders, and the stress-induced exacerbation of seizure activity in epileptic patients.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
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Adrenergic alpha-Antagonists / pharmacology
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Adrenergic beta-Antagonists / pharmacology
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Aging
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Amygdala / cytology
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Amygdala / drug effects*
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Amygdala / metabolism
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Amygdala / physiopathology
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Anesthetics, Local / pharmacology
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Animals
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Animals, Newborn
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Bicuculline / pharmacology
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Body Weight
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Dose-Response Relationship, Drug
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Drug Interactions
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Estrenes / pharmacology
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Excitatory Amino Acid Antagonists
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GABA Antagonists / pharmacology*
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Imidazoles / pharmacology
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In Vitro Techniques
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Isoquinolines / metabolism
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Male
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Membrane Potentials / drug effects
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Morpholines / pharmacology
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Neural Inhibition / drug effects
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Neurons / drug effects
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Neurons / physiology
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Norepinephrine / pharmacology
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Patch-Clamp Techniques / methods
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Phosphodiesterase Inhibitors / pharmacology
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Propranolol / pharmacology
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Pyrrolidinones / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Adrenergic, alpha-1 / metabolism*
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Restraint, Physical / methods
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Stress, Physiological / metabolism*
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Tetrahydronaphthalenes / pharmacology
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Tetrodotoxin / pharmacology
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Time Factors
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gamma-Aminobutyric Acid / metabolism*
Substances
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(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid
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A 61603
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Adrenergic alpha-Antagonists
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Adrenergic beta-Antagonists
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Anesthetics, Local
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Estrenes
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Excitatory Amino Acid Antagonists
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GABA Antagonists
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Imidazoles
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Isoquinolines
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Morpholines
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Phosphodiesterase Inhibitors
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Pyrrolidinones
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Receptors, Adrenergic, alpha-1
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Tetrahydronaphthalenes
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1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
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U 73343
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Tetrodotoxin
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gamma-Aminobutyric Acid
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6-Cyano-7-nitroquinoxaline-2,3-dione
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2-Amino-5-phosphonovalerate
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lucifer yellow
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Propranolol
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Norepinephrine
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Bicuculline