Corticotrophin Releasing Factor-Induced Synaptic Plasticity in the Amygdala Translates Stress into Emotional Disorders

Donald G. Rainnie, Richard Bergeron, Tammy J. Sajdyk, Madhvi Patil, Donald R. Gehlert, Anantha Shekhar

Research output: Contribution to journalArticle

224 Citations (Scopus)

Abstract

The amygdala is involved in the associative processes for both appetitive and aversive emotions, and its function is modulated by stress hormones. The neuropeptide corticotrophin releasing factor (CRF) is released during stress and has been linked to many stress-related behavioral, autonomic, and endocrine responses. In the present study, nonanxiety-inducing doses of a potent CRF type 1 and 2 receptor agonist, urocortin (Ucn), was infused locally into the basolateral amygdala (BLA) of rats. After 5 daily injections of Ucn, the animals developed anxiety-like responses in behavioral tests. Intravenous administration of the anxiogenic agent sodium lactate elicited robust increases in blood pressure, respiratory rate, and heart rate. Furthermore, in the absence of any additional Ucn treatment, these behavioral and autonomic responses persisted for >30 d. Whole-cell patch-clamp recordings from BLA neurons of these hyper-reactive animals revealed a pronounced reduction in both spontaneous and stimulation-evoked IPSPs, leading to a hyperexcitability of the BLA network. This Ucn-induced plasticity appears to be dependent on NMDA receptor and subsequent calcium-calmodulin-dependent protein kinase II (CaMKII) activation, because it is blocked by pretreatment with NMDA receptor antagonists and by coadministration of CaMKII inhibitors. Our results show for the first time a stress peptide-induced behavioral syndrome that can be correlated with cellular mechanisms of neural plasticity, a novel mechanism that may explain the etiological role of stress in several chronic psychiatric and medical disorders.

Original languageEnglish
Pages (from-to)3471-3479
Number of pages9
JournalJournal of Neuroscience
Volume24
Issue number14
DOIs
StatePublished - Apr 7 2004

Fingerprint

Urocortins
Neuronal Plasticity
Corticotropin-Releasing Hormone
Amygdala
Psychological Stress
Calcium-Calmodulin-Dependent Protein Kinase Type 2
N-Methyl-D-Aspartate Receptors
Sodium Lactate
Inhibitory Postsynaptic Potentials
Calcium-Calmodulin-Dependent Protein Kinases
Protein Kinase Inhibitors
Respiratory Rate
Neuropeptides
Intravenous Administration
Psychiatry
Emotions
Anxiety
Heart Rate
Hormones
Blood Pressure

Keywords

  • Anxiety
  • Basolateral amygdala
  • in vitro
  • in vivo
  • Inhibition
  • Urocortin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Corticotrophin Releasing Factor-Induced Synaptic Plasticity in the Amygdala Translates Stress into Emotional Disorders. / Rainnie, Donald G.; Bergeron, Richard; Sajdyk, Tammy J.; Patil, Madhvi; Gehlert, Donald R.; Shekhar, Anantha.

In: Journal of Neuroscience, Vol. 24, No. 14, 07.04.2004, p. 3471-3479.

Research output: Contribution to journalArticle

Rainnie, Donald G. ; Bergeron, Richard ; Sajdyk, Tammy J. ; Patil, Madhvi ; Gehlert, Donald R. ; Shekhar, Anantha. / Corticotrophin Releasing Factor-Induced Synaptic Plasticity in the Amygdala Translates Stress into Emotional Disorders. In: Journal of Neuroscience. 2004 ; Vol. 24, No. 14. pp. 3471-3479.
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