Non-specific inhibition of dopamine receptor agonist-induced behaviour by the tachykinin NK1 receptor antagonist CP-99,994 in guinea-pigs.
Evidence that tachykinin NK1 receptors selectively modulate activity in the mesolimbic dopamine pathway suggests an antipsychotic potential for tachykinin NK1 receptor antagonists. We investigated the ability of the antagonist CP-99,994 (and the less active enantiomer CP-100,263) to block dopamine receptor agonist-induced behaviour in guinea-pigs. The active dose range for inhibition of [Sar9,Met(O2)11]substance P-induced behaviour by CP-99,994 was 1-3 mg/kg s.c. The same doses of CP-100,263 were without effect. In contrast, both CP-99,994 (20 or 30 mg/kg) and CP-100,263 (10-30 mg/kg) antagonised behavioural stimulation induced by the dopamine receptor agonists amphetamine (1 mg/kg i.p.) or (+)-PHNO ((+)-4-propyl-9-hydroxy-naphthoxazine hydrochloride; 0.1 mg/kg s.c.). Lower doses of CP-99,994 or CP-100,263 were not active. These findings do not support the proposal that tachykinin NK1 receptors in the terminal projection area of the mesolimbic system can modify dopamine-mediated behaviour.
Rupniak
N M
NM
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Jackson
A
A
D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D006120:Grooming / Q000187:drug effects; D006168:Guinea Pigs; D006220:Haloperidol / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D015288:Neurokinin A / Q000037:antagonists & inhibitors*; D064729:Neurokinin-1 Receptor Antagonists; D010078:Oxazines / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D018040:Receptors, Neurokinin-1 / Q000819:agonists; D013237:Stereoisomerism; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology
D018491:Dopamine Agonists; D064729:Neurokinin-1 Receptor Antagonists; D010078:Oxazines; D010880:Piperidines; D018040:Receptors, Neurokinin-1; C062618:substance P, Sar(9)-Met(O2)(11)-; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; C042631:naxagolide; D013373:Substance P; D015288:Neurokinin A; D000661:Amphetamine; D006220:Haloperidol