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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effects of acetylcholine agonists and antagonists on yawning and analgesia in the rat.

The ability of acetylcholine muscarinic agonists, injected subcutaneously (s.c.) to elicit yawning and analgesia (tail-flick response) in rats was examined. Yawning was elicited by physostigmine, RS86 and pilocarpine with an inverted 'U'-shaped dose-response relationship; maximal effects occurred at 0.1, 0.5 and 2.0 mg/kg respectively. Neostigmine (0.05-0.2 mg/kg); arecoline (0.5-2.0 mg/kg); bethanecol (0.1-10 mg/kg) and McN-A-343 (5-20 mg/kg) had marginal or no activity. In contrast, dose-related analgesia was obtained following oxotremorine (0.01-0.3 mg/kg) and arecoline (0.5-4.0 mg/kg) and physostigmine (0.1-0.4 mg/kg), RS86 (0.25-2.5 mg/kg) and pilocarpine (0.5-8.0 mg/kg). The effects of acetylcholine antagonists on physostigmine-induced yawning and physostigmine-induced analgesia were also investigated. Following their s.c. injection, trihexyphenidyl, atropine, dicyclomine, secoverine and methylatropine but not pirenzepine, inhibited both yawning and analgesia; there were clear differences in their potencies on the two responses. Pirenzepine, intracerebroventricularly (i.c.v.), inhibited yawning (ED50 value 5.7 micrograms/rat) but not analgesia (3-100 micrograms/rat). The results are discussed in terms of a possible functional differentiation of central muscarinic receptors.[1]


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