Effects of SR 48692, a selective non-peptide neurotensin receptor antagonist, on two dopamine-dependent behavioural responses in mice and rats.
One major mechanism underlying the central action of neurotensin is an interaction with the function of dopamine (DA)-containing neurons. In addition, direct or indirect DA agonists have been reported to promote neurotensin release. We have found that SR 48692, a non-peptide neurotensin receptor antagonist (0.04-0.64 mg/kg orally), antagonizes (50-65%) yawning induced by apomorphine (0.07 mg/kg SC) or bromocriptine (2 mg/kg IP) in rats, and turning behaviour induced by intrastriatal injection of apomorphine (0.25 micrograms), (+) SKF 38393 (0.1 micrograms), bromocriptine (0.01 ng) or (+) amphetamine (10 micrograms) in mice. Other apomorphine-induced effects in mice and rats such as climbing, hypothermia, hypo- and hyper-locomotion, penile erections and stereotypies were not significantly modified by SR 48692. Taken together, these data suggest that neurotensin may play a permissive role in the expression of some but not all behavioural responses to DA receptor stimulation.
Poncelet
M
M
Sanofi Recherche, Neuropsychiatry Department, Montpellier, France.
Souilhac
J
J
Gueudet
C
C
Terranova
J P
JP
Gully
D
D
Le Fur
G
G
Soubrié
P
P
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001971:Bromocriptine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010410:Penile Erection / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors*; D013239:Stereotyped Behavior / Q000187:drug effects; D015000:Yawning / Q000187:drug effects
D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; C079087:SR 48692; D001971:Bromocriptine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D001058:Apomorphine; D004298:Dopamine