Behavioural tolerance to arecoline in rats: cross-tolerance to oxotremorine and prevention by pretreatment with atropine.

In two experiments tolerance development to the effects of arecoline on operant responding for a water reward was shown to be dose-dependent, complete tolerance developing to a daily dose of 4 mg/kg, but only partial tolerance developing to a daily dose of 8 mg/kg. However, rats chronically treated with the higher dose of arecoline were least affected by a challenge dose of oxotremorine (0.2 mg/kg); i.e. the high dose group exhibited the greatest cross-tolerance to oxotremorine. Moreover, atropine (4 mg/kg) pretreatment prior to arecoline (4 mg/kg) prevented cross-tolerance to oxotremorine, indicating that dispositional mechanisms are unlikely to be involved in tolerance to arecoline.