The effect of chronic CRF1 receptor blockade on the central CCK systems of Fawn-Hooded rats

Daniel J. Lodge, Andrew J. Lawrence

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Corticotropin-releasing factor (CRF) is a neuropeptide associated with the integration of physiological and behavioural responses to stress. More recently, the CRF system has been implicated in the modulation of affective state and in the actions of abused drugs, including ethanol. As such, we have previously demonstrated that the selective, centrally acting CRF1 receptor antagonist antalarmin displays an acute anxiolytic action and reduces established volitional ethanol consumption in isolation-reared Fawn-Hooded rats [Neuroscience 117 (2003) 243]. Similar to CRF, CCK is a neuropeptide found in high abundance throughout the neuraxis and is involved in the control of appetite, anxiety, reward and hormone regulation. Given the similar functions regulated by the neuropeptides CRF and CCK, it is of importance to determine whether interactions exist between these neuropeptides. Therefore, the aim of the present study was to examine the effects of chronic CRF1 receptor blockade on the central CCK systems of Fawn-Hooded (FH) rats. Thus, bi-daily antalarmin treatment (20 mg/kg ip) induced a significant increase in CCK-B receptor-binding density throughout the neuraxis, indicative of either a global increase in receptor number or an increase in receptor affinity. In contrast, chronic antalarmin treatment resulted in bidirectional, region-specific changes in preproCCK messenger ribonucleic acid (mRNA) expression. Interestingly, this effect on CCK mRNA expression was restricted to the thalamocortico-limbic system, which is intimately involved in the integration of emotive behaviour and central reward processing. Therefore, these data provide clear evidence of the ability of chronic CRF1 receptor blockade to significantly influence the central CCK systems of the rat.

Original languageEnglish (US)
Pages (from-to)27-33
Number of pages7
JournalRegulatory Peptides
Volume116
Issue number1-3
DOIs
StatePublished - Nov 15 2003
Externally publishedYes

Keywords

  • Antalarmin
  • CRF
  • Neurochemistry

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Clinical Biochemistry
  • Cellular and Molecular Neuroscience

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