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The behavioural effects of corticotropin-releasing factor-related peptides in rats
Authors:D. N. C. Jones  R. Kortekaas  Paula D. Slade  Derek N. Middlemiss  Jim J. Hagan
Affiliation:(1) Neuroscience Research, SmithKline Beecham Pharmaceuticals plc, New Frontiers Science Park, Third Ave., Harlow, Essex CM19 5AW, UK e-mail: declan-jones-1@sbphrd.com, Fax: +44-1279-622230, GB
Abstract:
The present study determined the behavioural effects of the corticotropin releasing factor (CRF)-related peptides, human/rat CRF (h/rCRF), ovine CRF (oCRF), sauvagine (SAUV), urotensin I (UT) and the recently discovered neuropeptide, rat urocortin (rUCN). All of the peptides dose-dependently increased motor activity in a familiar environment and reduced feeding in hungry rats. There was no apparent relationship between potency/affinity at CRF2 receptors and effects in these two tests. In a comparison of h/rCRF and rUCN upon discrete spontaneous behaviours, both peptides (3.0 μg ICV) increased activity and grooming, induced a fore-paw tremor and reduced the incidence of motionlessness. However, h/rCRF reduced motionlessness to a greater extent and was a more potent inducer of defaecation, weight loss, oral movements and fore-paw tremor than rUCN. In the elevated X maze, both h/rCRF and rUCN (1.0 μg ICV) had anxiogenic-like effects upon behaviour. In contrast, h/rCRF (1.0 μg ICV), but not rUCN (1.0–10 μg ICV) increased the startle response to an acoustic stimulus. In summary, all the CRF-related peptides increased motor activity and reduced feeding in rats in a similar manner and both rUCN and h/rCRF induced anxiogenesis. However, there were some behavioural differences between rUCN and h/rCRF which require further study. Further pharmacological investigation of the role of CRF receptor subtypes requires the use of subtype selective antagonists. Received: 8 January 1997/Final version: 24 January 1998
Keywords:Sauvagine  Urotensin I  Corticotropin-releasing factor  Urocortin  Hypophagia  Anxiogenesis  Hyperactivity
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