Evidence for a model of activation of central sigma systems.
Evidence for a drug-induced activation of central sigma systems is presented. The model is the locomotor activation initiated by a subcutaneous (SC) challenge of 1.6 mg/kg of (+)-butaclamol, (+)-BUT, given 30 min before 10 mg/kg SC of (-)-N-allylnormetazocine, (-)-NAN, in Sprague-Dawley male rats which have been pretreated with four daily injections of 10 mg/kg SC of (-)-NAN. The locomotor activation is characterized by an initial 20 min period of retropulsion and sideways-circling followed by 90 to 100 min of forward locomotion. The locomotor syndrome is antagonized by 10 mg/kg of (+/-)-BMY 14802, 20 mg/kg of rimcazole, and 0.2 mg/kg of haloperidol, but not by 0.04 mg/kg of R(+)SCH23390, 100 mg/kg of S(-)sulpiride, 10 mg/kg of naltrexone, or 2.5 mg/kg of MR2266. The data suggest that the manifestation of the (+)-BUT/(-)-NAN-induced syndrome depends upon intact transmission at central sigma sites.
Iwamoto
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Department of Pharmacology, University of Kentucky College of Medicine, Lexington 40536.
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001575:Benzomorphans / Q000494:pharmacology; D002069:Butaclamol / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D018492:Dopamine Antagonists; D006220:Haloperidol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017480:Receptors, sigma; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D001575:Benzomorphans; D002227:Carbazoles; D018492:Dopamine Antagonists; D009292:Narcotic Antagonists; D011743:Pyrimidines; D011957:Receptors, Opioid; D017480:Receptors, sigma; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; C027247:MR 2266; D009271:Naltrexone; C012134:SK&F 10047; D013469:Sulpiride; D002069:Butaclamol; C034931:rimcazole; D010620:Phenazocine; D006220:Haloperidol