The behavioural effects of corticotropin-releasing factor-related peptides in rats.
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 microg i.c.v.) 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 microg i.c.v.) had anxiogenic-like effects upon behaviour. In contrast, h/rCRF (1.0 microg i.c.v.), but not rUCN (1.0-10 microg i.c.v.) 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.
Neuroscience Research, SmithKline Beecham Pharmaceuticals plc, Harlow, Essex, UK. declan-jones-1@sbphrd.com
D N
DN
Jones
R
R
Kortekaas
P D
PD
Slade
D N
DN
Middlemiss
J J
JJ
Hagan
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects*; D018782:Maze Learning / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects; D013217:Starvation; D054832:Urocortins; D000159:Vestibulocochlear Nerve / Q000187:drug effects
C101531:CRF receptor type 2; D010455:Peptides; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone