Dopamine receptor mechanisms mediate corticotropin-releasing factor-induced long-term potentiation in the rat amygdala following cocaine withdrawal

Balaji Krishnan, Marjorie Centeno, Sebastian Pollandt, Yu Fu, Kathy Genzer, Jie Liu, Joel P. Gallagher, Patricia Shinnick-Gallagher

Research output: Contribution to journalArticle

23 Scopus citations


Corticotropin-releasing factor (CRF) in the amygdala is involved in stress responses. Moreover, dopaminergic neurotransmission in the brain reward system including the amygdala plays a significant role in the pathology of cocaine addiction. The present study analysed CRF-induced synaptic plasticity, its pharmacological sensitivity and interactions with the dopamine (DA) system in the basolateral to lateral capsula central amygdala (lcCeA) pathway after a 2-week withdrawal from repeated cocaine administration. A physiologically relevant CRF concentration (25 nm) induced long-term potentiation (LTP) that was enhanced after cocaine withdrawal. In saline-treated rats, CRF-induced LTP was mediated through N-methyl-d-aspartate (NMDA) receptors, L-type voltage-gated calcium channels (L-VGCCs) and CRF1 receptors. However, in cocaine-withdrawn animals, activation of CRF1 and CRF2 receptors was found to enhance LTP. This enhanced CRF-induced LTP after cocaine withdrawal was mediated through endogenous activation of both D1- and D2-like receptors. Furthermore, expression of the D1 receptor (D1R) but not the D2R, D3R, D4R or D5R was significantly increased after cocaine withdrawal. CRF 1 but not CRF2 protein expression was increased, suggesting that elevated levels of these proteins contributed to the enhancement of CRF-induced LTP during cocaine withdrawal. CRF interactions with the DA system in the amygdala may represent a fundamental neurochemical and cellular mechanism linking stress to cocaine-induced neuronal plasticity.

Original languageEnglish (US)
Pages (from-to)1027-1042
Number of pages16
JournalEuropean Journal of Neuroscience
Issue number6
StatePublished - Mar 1 2010



  • Basolateral amygdala to central amygdala
  • CRF receptors
  • Cocaine withdrawal
  • Field EPSP
  • GABAergic inhibition
  • Synaptic transmission

ASJC Scopus subject areas

  • Neuroscience(all)

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