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Restoration of glutamatergic transmission by dopamine D4 receptors in stressed animals.

Abstract
The prefrontal cortex (PFC), a key brain region for cognitive and emotional processes, is highly regulated by dopaminergic inputs. The dopamine D4 receptor, which is enriched in PFC, has been implicated in mental disorders, such as attention deficit-hyperactivity disorder and schizophrenia. Recently we have found homeostatic regulation of AMPA receptor-mediated synaptic transmission in PFC pyramidal neurons by the D4 receptor, providing a potential mechanism for D4 in stabilizing cortical excitability. Because stress is tightly linked to adaptive and maladaptive changes associated with mental health and disorders, we examined the synaptic actions of D4 in stressed rats. We found that neural excitability was elevated by acute stress and dampened by repeated stress. D4 activation produced a potent reduction of excitatory transmission in acutely stressed animals and a marked increase of excitatory transmission in repeatedly stressed animals. These effects of D4 targeted GluA2-lacking AMPA receptors and relied on the bi-directional regulation of calcium/calmodulin kinase II activity. The restoration of PFC glutamatergic transmission in stress conditions may enable D4 receptors to serve as a synaptic stabilizer in normal and pathological conditions.
AuthorsEunice Y Yuen, Ping Zhong, Xiangning Li, Jing Wei, Zhen Yan
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 288 Issue 36 Pg. 26112-26120 (Sep 06 2013) ISSN: 1083-351X [Electronic] United States
PMID23884421 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Receptors, AMPA
  • Receptors, Dopamine D4
  • Glutamic Acid
  • glutamate receptor ionotropic, AMPA 2
Topics
  • Animals
  • Glutamic Acid (metabolism)
  • Male
  • Prefrontal Cortex (metabolism, pathology, physiopathology)
  • Pyramidal Cells (metabolism, pathology, physiopathology)
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA (metabolism)
  • Receptors, Dopamine D4 (metabolism)
  • Stress, Psychological (metabolism, pathology, physiopathology)
  • Synaptic Transmission

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