The corticotropin-releasing factor receptor 1 antagonist CP-154,526 reverses stress-induced learning deficits in mice

The corticotropin-releasing factor receptor 1 antagonist CP-154,526 reverses stress-induced... The neuropeptide corticotropin-releasing factor (CRF) coordinates the endocrine responses to stress as a major physiological regulator of the hypothalamic–pituitary–adrenal axis. We assessed the effect of the non-peptidergic CRF receptor 1 antagonist CP-154,526 on stress-induced changes in context-dependent fear conditioning and hippocampal synaptic plasticity. The learning impairment of mice trained immediately after 1 h immobilization could be overcome by preinjection of CP-154,526 before exposure to immobilization. Exposure to acute stress reduced the amount of autophosphorylated Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) in the hippocampal CA1 area. When animals were pretreated with CP-154,526 before immobilization, the amount of hippocampal autophosphorylated CaMKII was elevated. Electrophysiological studies in the hippocampal CA1 region of stressed animals revealed no significant effects of the CP-154,526 pretreatment on long-term potentiation but a significant elevation of paired-pulse facilitation (PPF) was observed. The CP-154,526-induced enhancements in fear conditioning and PPF could be prevented by the selective CaMKII inhibitor KN-62. Our results demonstrated that learning impairment after acute stress was antagonized by CP-154,526 pretreatment. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Behavioural Brain Research Elsevier

The corticotropin-releasing factor receptor 1 antagonist CP-154,526 reverses stress-induced learning deficits in mice

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Publisher
Elsevier
Copyright
Copyright © 2002 Elsevier Science B.V.
ISSN
0166-4328
DOI
10.1016/S0166-4328(02)00244-9
Publisher site
See Article on Publisher Site

Abstract

The neuropeptide corticotropin-releasing factor (CRF) coordinates the endocrine responses to stress as a major physiological regulator of the hypothalamic–pituitary–adrenal axis. We assessed the effect of the non-peptidergic CRF receptor 1 antagonist CP-154,526 on stress-induced changes in context-dependent fear conditioning and hippocampal synaptic plasticity. The learning impairment of mice trained immediately after 1 h immobilization could be overcome by preinjection of CP-154,526 before exposure to immobilization. Exposure to acute stress reduced the amount of autophosphorylated Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) in the hippocampal CA1 area. When animals were pretreated with CP-154,526 before immobilization, the amount of hippocampal autophosphorylated CaMKII was elevated. Electrophysiological studies in the hippocampal CA1 region of stressed animals revealed no significant effects of the CP-154,526 pretreatment on long-term potentiation but a significant elevation of paired-pulse facilitation (PPF) was observed. The CP-154,526-induced enhancements in fear conditioning and PPF could be prevented by the selective CaMKII inhibitor KN-62. Our results demonstrated that learning impairment after acute stress was antagonized by CP-154,526 pretreatment.

Journal

Behavioural Brain ResearchElsevier

Published: Jan 22, 2003

References

  • Learning-specific, time-dependent increases in hippocampal Ca 2+ /calmodulin-dependent protein kinase II activity and AMPA GluR1 subunit immunoreactivity
    Cammarota, M.; Bernabeu, R.; Levi De Stein, M.; Izquierdo, I.; Medina, J.H.
  • Hippocampus and context in classical conditioning
    Holland, P.C.; Bouton, M.E.
  • Evaluation of RU28318 and RU40555 as selective mineralocorticoid receptor and glucocorticoid receptor antagonists, respectively: receptor measures and functional studies
    Kim, P.J.; Cole, M.A.; Kalman, B.A.; Spencer, R.L.
  • Intra-amygdala injections of corticotropin releasing factor facilitate inhibitory avoidance learning and reduce exploratory behavior in rats
    Liang, K.C.; Lee, E.H.
  • Impairment of conditioned contextual fear of C57BL/6J mice by intracerebral injections of the NMDA receptor antagonist APV
    Stiedl, O.; Birkenfeld, K.; Palve, M.; Spiess, J.

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