title: Inherited, selective hypoanalgesic response to cytisine in the tail-flick test in CF-1 mice.
abstract: This study extends the pharmacological characterization of the genotype- dependent difference in analgesic responsiveness to neuronal nicotinic agonists between CD-1 and CF-1 strains of mice. Acute analgesic potency of cytisine measured by the tail-flick assay differed by > 3200-fold between CD-1 and CF-1 outbred strains of mice. Analgesic non-responsiveness of the CF-1 strain was pharmacologically selective. Morphine produced a dose-dependent analgesic response of similar magnitude in both strains. Other pharmacological actions of cytisine, including inhibition of locomotor activity, induction of seizures and lethality, did not differ between these strains. Hyporesponsiveness to the analgesic action of both nicotine and cytisine was observed in two different CF-1 sublines. Biodistribution of [3H]cytisine in blood did not differ between the CF-1 and CD-1 strains. These pharmacological characteristics indicate that the CD-1-CF-1 strain pair provides a useful pharmacogenetic tool for investigating the mechanistic bases of analgesia induced by nicotinic cholinergic agonists.
authors.affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: Seale
authors.forename: R
authors.initials: R
authors.lastname: Nael
authors.forename: S
authors.initials: S
authors.lastname: Singh
authors.forename: G
authors.initials: G
authors.lastname: Basmadjian
mesh_terms: D000470:Alkaloids / Q000493:pharmacokinetics / Q000494:pharmacology*; D000698:Analgesia; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001392:Azocines; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010146:Pain / Q000235:genetics* / Q000523:psychology; D010147:Pain Measurement / Q000187:drug effects*; D011807:Quinolizines; D011930:Reaction Time / Q000187:drug effects; D014018:Tissue Distribution; D000093843:Quinolizidine Alkaloids
chemical_list: D000470:Alkaloids; D000701:Analgesics, Opioid; D001392:Azocines; D018679:Cholinergic Agonists; D009020:Morphine; D018722:Nicotinic Agonists; D011807:Quinolizines; C004712:cytisine; D000093843:Quinolizidine Alkaloids