INHERITED, SELECTIVE HYPOANALGESIC RESPONSE TO CYTISINE IN THE TAIL-FLICK TEST IN CF-1 MICE

THIS study extends the pharmacological characterization of the genotyp e-dependent difference in analgesic responsiveness to neuronal nicotin ic agonists between CD-1 and CF-1 strains of mice. Acute analgesic pot ency of cytisine measured by the tail-flick assay differed by > 3200-f old between CD-1 and CF-1 outbred strains of mice. Analgesic non-respo nsiveness 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 inh ibition of locomotor activity, induction of seizures and lethality, di d not differ between these strains. Hyporesponsiveness to the analgesi c action of both nicotine and cytisine was observed in two different C F-1 sublines. Biodistribution of [H-3]cytisine in blood did not differ between the CF-1 and CD-1 strains. These pharmacological characterist ics indicate that the CD-1-CF-1 strain pair provides a useful pharmaco genetic tool for investigating the mechanistic bases of analgesia indu ced by nicotinic cholinergic agonists.