The CRF-like peptide urocortin greatly attenuates loss of extracellular striatal dopamine in rat models of Parkinson's disease by activating CRF1 receptors

Abuirmeileh, A., Harkavyi, A., Kingsbury, A.E., Lever, R. and Whitton, P.S. (2009) The CRF-like peptide urocortin greatly attenuates loss of extracellular striatal dopamine in rat models of Parkinson's disease by activating CRF1 receptors. European Journal of Pharmacology, 604 (1-3). pp. 45-50. 10.1016/j.ejphar.2008.11.009.

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DOI: 10.1016/j.ejphar.2008.11.009

Abstract

We have recently observed that the corticotrophin releasing factor (CRF) related peptide urocortin reverses key features of nigrostriatal damage in two paradigms of Parkinson's disease. Here we have studied whether these effects are supported by a retention of striatal basal and evoked extracellular dopamine and the receptor(s) that may mediate this effect. Fourteen days following stereotaxic injections of 6-hydroxydopamine (6-OHDA) or lipopolysaccharide (LPS) and urocortin, extracellular dopamine levels in striata ipsilateral to injection sites of 6-OHDA/LPS and urocortin treated rats were comparable with sham injected rats, whilst rats given 6-OHDA/LPS and vehicle had considerably lower dopamine levels. Striatal dopamine levels in animals where urocortin injection was delayed by seven days were only modestly decreased compared to animals receiving 6-OHDA/LPS and urocortin concomitantly. Additionally, the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were also preserved in dialysates from urocortin treated rats. The effects of urocortin were entirely blocked by the non-selective CRF receptor antagonist α-helical CRF as well as the selective CRF1 antagonist NBI 27914 and were not replicated by the selective CRF2 ligand urocortin III. In the substantia nigra tissue dopamine changes mirrored those seen in striatal extracellular dopamine. Our data strongly suggest that urocortin is capable of maintaining adequate nigrostriatal function in vivo via CRF1 receptors following. neurotoxic challenge.

Item Type:Article
Uncontrolled Keywords:Urocortin; 6-hydroxydopamine; Lipopolysaccaride; Dopamine; In vivo microdialysis
Departments, units and centres:Department of Pharmacology > Department of Pharmacology
ID Code:3093
Journal or Publication Title:European Journal of Pharmacology
Deposited By:Library Staff
Deposited On:20 Apr 2012 16:46
Last Modified:20 Apr 2012 16:46

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