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- W1481012017 abstract "Background and Purpose The negative affective states of withdrawal involve the recruitment of brain and peripheral stress circuitry [noradrenergic activity, induction of the hypothalamic–pituitary–adrenocortical ( HPA ) axis and activation of heat shock proteins ( H sps)]. Corticotropin‐releasing factor ( CRF ) pathways are important mediators in the negative symptoms of opioid withdrawal. We performed a series of experiments to characterize the role of the CRF 1 receptor in the response of stress systems to morphine withdrawal and its effect in the heart using genetically engineered mice lacking functional CRF 1 receptors. Experimental Approach Wild‐type and CRF 1 receptor‐knockout mice were treated with increasing doses of morphine. Precipitated withdrawal was induced by naloxone. Plasma adrenocorticotropic hormone ( ACTH ) and corticosterone levels, the expression of myocardial H sp27, H sp27 phosphorylated at S er 82 , membrane ( MB )‐ COMT , soluble ( S )‐ COMT protein and NA turnover were evaluated by RIA , immunoblotting and HPLC . Key Results During morphine withdrawal we observed an enhancement of NA turnover in parallel with an increase in mean arterial blood pressure (MAP) and heart rate (HR) in wild‐type mice. In addition, naloxone‐precipitated morphine withdrawal induced an activation of HPA axis and Hsp27. The principal finding of the present study was that plasma ACTH and corticosterone levels, MB‐COMT, S‐COMT, NA turnover, and Hsp27 expression and activation observed during morphine withdrawal were significantly inhibited in the CRF 1 receptor‐knockout mice. Conclusion and Implications Our results demonstrate that CRF / CRF 1 receptor activation may contribute to stress‐induced cardiovascular dysfunction after naloxone‐precipitated morphine withdrawal and suggest that CRF / CRF 1 receptor pathways could contribute to cardiovascular disease associated with opioid addiction." @default.
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- W1481012017 date "2014-01-13" @default.
- W1481012017 modified "2023-10-18" @default.
- W1481012017 title "Corticotropin‐releasing factor (<scp>CRF</scp>) receptor‐1 is involved in cardiac noradrenergic activity observed during naloxone‐precipitated morphine withdrawal" @default.
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- W1481012017 doi "https://doi.org/10.1111/bph.12511" @default.
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