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 journalArticlepeer-review

    26 Scopus citations

    Abstract

    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 However, in cocaine-withdrawn animals, activation of CRF1 and CRF2 receptors was found to enhance LTP.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
    Volume31
    Issue number6
    DOIs
    StatePublished - Mar 2010

    Keywords

    • 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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