PMID- 11298806
OWN - NLM
STAT- MEDLINE
DCOM- 20010621
LR  - 20191210
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 13
IP  - 7
DP  - 2001 Apr
TI  - SB-334867, a selective orexin-1 receptor antagonist, enhances behavioural satiety 
      and blocks the hyperphagic effect of orexin-A in rats.
PG  - 1444-52
AB  - Intracerebroventricular (i.c.v.) administration of the novel hypothalamic 
      neuropeptide orexin-A stimulates food intake in rats, and delays the onset of 
      behavioural satiety (i.e. the natural transition from feeding to resting). 
      Furthermore, preliminary findings with the selective orexin-1 receptor 
      antagonist, SB-334867, suggest that orexin-A regulation of food intake is 
      mediated via the orexin-1 receptor. At present, however, little is known about 
      either the intrinsic effects of SB-334867 on the normal structure of feeding 
      behaviour, or its effects upon orexin-A-induced behavioural change. In the 
      present study, we have employed a continuous monitoring technique to characterize 
      the effects of SB-334867 (3-30 mg/kg, i.p.) on the microstructure of rat 
      behaviour during a 1-h test with palatable wet mash. Administered alone, 
      SB-334867 (30 mg/kg, but not lower doses) significantly reduced food intake and 
      most active behaviours (eating, grooming, sniffing, locomotion and rearing), 
      while increasing resting. Although suggestive of a behaviourally nonselective 
      (i.e. sedative) action, the structure of feeding behaviour was well-preserved at 
      this dose level, with the reduction in behavioural output clearly attributable to 
      an earlier onset of behavioural satiety. As previously reported, orexin-A (10 
      microg per rat i.c.v.) stimulated food intake, increased grooming and delayed the 
      onset of behavioural satiety. Pretreatment with SB-334867 dose-dependently 
      blocked these effects of orexin-A, with significant antagonism evident at dose 
      levels (3-10 mg/kg) below those required to produce intrinsic behavioural effects 
      under present test conditions. Together, these findings strongly support the view 
      that orexin-A is involved in the regulation of feeding patterns and that this 
      influence is mediated through the orexin-1 receptor.
FAU - Rodgers, R J
AU  - Rodgers RJ
AD  - School of Psychology, University of Leeds, UK. johnr@psychology.leeds.ac.uk
FAU - Halford, J C
AU  - Halford JC
FAU - Nunes de Souza, R L
AU  - Nunes de Souza RL
FAU - Canto de Souza, A L
AU  - Canto de Souza AL
FAU - Piper, D C
AU  - Piper DC
FAU - Arch, J R
AU  - Arch JR
FAU - Upton, N
AU  - Upton N
FAU - Porter, R A
AU  - Porter RA
FAU - Johns, A
AU  - Johns A
FAU - Blundell, J E
AU  - Blundell JE
LA  - eng
PT  - Journal Article
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea)
RN  - 0 (Benzoxazoles)
RN  - 0 (Carrier Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Naphthyridines)
RN  - 0 (Neuropeptides)
RN  - 0 (Orexin Receptors)
RN  - 0 (Orexins)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Receptors, Neuropeptide)
RN  - 8W8T17847W (Urea)
SB  - IM
MH  - Animals
MH  - Appetitive Behavior/drug effects
MH  - Benzoxazoles/*pharmacology
MH  - Body Weight
MH  - Carrier Proteins/*pharmacology
MH  - Eating/drug effects
MH  - Hyperphagia/chemically induced/*metabolism
MH  - Injections, Intraventricular
MH  - *Intracellular Signaling Peptides and Proteins
MH  - Male
MH  - Naphthyridines
MH  - Neuropeptides/*pharmacology
MH  - Orexin Receptors
MH  - Orexins
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Receptors, G-Protein-Coupled
MH  - Receptors, Neuropeptide/*antagonists & inhibitors/metabolism
MH  - Satiety Response/*drug effects
MH  - Urea/analogs & derivatives/*pharmacology
EDAT- 2001/04/12 10:00
MHDA- 2001/06/22 10:01
CRDT- 2001/04/12 10:00
PHST- 2001/04/12 10:00 [pubmed]
PHST- 2001/06/22 10:01 [medline]
PHST- 2001/04/12 10:00 [entrez]
AID - ejn1518 [pii]
AID - 10.1046/j.0953-816x.2001.01518.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2001 Apr;13(7):1444-52. doi: 10.1046/j.0953-816x.2001.01518.x.