The neurotensin antagonist SR 48692 fails to modify the behavioural responses to a dopamine D1 receptor agonist in the rat.
The effects of the neurotensin antagonist SR 48692 on the behavioural responses to the dopamine D1 receptor agonist SKF 38393 were investigated in the rat. SKF 38393 (5 mg/kg s.c.) elicited vacuous chewing movements (VCMs) and grooming, which were unaffected by SR 48692 (50 micrograms/kg i.p.). The dopamine D2 receptor antagonist raclopride (0.5 mg/kg s.c.) elicited a small increase in VCMs in animals treated with SR 48692 and attenuated grooming induced by SKF 38393. These effects were not otherwise modified by SR 48692. We conclude that VCMs induced by acute administration of a dopamine D1 receptor agonist are unlikely to be dependent upon enhanced release of neurotensin in the striatum or its projections. This is contrast to the vacuous chewing response which emerges following chronic administration of neuroleptics, which is attenuated by neurotensin receptor antagonist. Thus, inasmuch as chronic neuroleptic-induced VCMs in the rat may be analogous to tardive dyskinesia in humans, the responses induced by acute administration of a D1 agonist to the rat cannot be used as a model of this disorder. Furthermore, the behavioural effects of chronic neuroleptic administration reflect more than a simple shift in the balance of D1 versus D2 receptor stimulation.
Stoessl
A J
AJ
Department of Clinical Neurological Sciences, University of Western Ontario, London, Canada. jon@thetis.pet.med.ubc.ca
James
K A
KA
Napier
B J
BJ
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D018492:Dopamine Antagonists / Q000494:pharmacology*; D008297:Male; D008409:Mastication / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors*; D012457:Salicylamides / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects*
D018492:Dopamine Antagonists; D011720:Pyrazoles; D011804:Quinolines; D017447:Receptors, Dopamine D1; D018028:Receptors, Neurotensin; D012457:Salicylamides; C079087:SR 48692; D020891:Raclopride; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine