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.
Jones
D N
DN
Neuroscience Research, SmithKline Beecham Pharmaceuticals plc, Harlow, Essex, UK. declan-jones-1@sbphrd.com
Kortekaas
R
R
Slade
P D
PD
Middlemiss
D N
DN
Hagan
J J
JJ
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