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

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 en...

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Bibliographic Details
Published in:The Journal of neuroscience 2004-04, Vol.24 (14), p.3471-3479
Main Authors: Rainnie, Donald G, Bergeron, Richard, Sajdyk, Tammy J, Patil, Madhvi, Gehlert, Donald R, Shekhar, Anantha
Format: Article
Language:English
Subjects:
Affective Symptoms - physiopathology
Amygdala - drug effects
Amygdala - metabolism
Amygdala - physiology
Animals
Anxiety - chemically induced
Anxiety - physiopathology
Behavioral/Systems/Cognitive
Blood Pressure - drug effects
Calcium - metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases - drug effects
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Corticotropin-Releasing Hormone - pharmacology
Drug Administration Routes
Drug Administration Schedule
Excitatory Postsynaptic Potentials - drug effects
Excitatory Postsynaptic Potentials - physiology
Heart Rate - drug effects
Male
Neuronal Plasticity - drug effects
Neuronal Plasticity - physiology
Neurons - drug effects
Neurons - metabolism
Patch-Clamp Techniques
Rats
Rats, Wistar
Receptors, Corticotropin-Releasing Hormone - agonists
Receptors, Corticotropin-Releasing Hormone - metabolism
Receptors, N-Methyl-D-Aspartate - metabolism
Sodium Lactate - pharmacology
Stress, Physiological - physiopathology
Synaptic Transmission - drug effects
Synaptic Transmission - physiology
Urocortins
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Summary: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.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.5740-03.2004