Cholinergic drug effects on antidepressant-induced behaviour in the forced swimming test

The contribution of anticholinergic effects to the action of desipramine and nomifensine was investigated in the forced swimming test in rats. The immobility time was reduced by high doses of atropine (10-25 mg/kg i.p.) and scopolamine (1.5 mg/kg i.p., 1 and 0.5 h before the test, respectively) and was unaffected by physostigmine (0.25-0.5 mg/kg i.p., 1 h before the test). Unlike atropine (25 mg/kg), scopolamine (1.5 mg/kg) increased motor activity (open-field). The anti-immobility effect of i.p. desipramine (20 or 30 mg/kg) and nomifensine (2.5 or 5 mg/kg), administered 24, 5 and 1 h before the test, was potentiated by scopolamine (0.5-1.0 mg/kg) and antagonized by physostigmine (0.25-0.5 mg/kg). The brain levels of desipramine and nomifensine were unaffected by scopolamine or physostigmine. Motor performance was impaired in rats treated with physostigmine and desipramine whereas hypermotility was observed in rats treated with scopolamine and nomifensine. The anti-immobility effect of atropine (25 mg/kg) and scopolamine (1.5 mg/kg) was not antagonized by physostigmine (0.5 mg/kg). These results indicate that anticholinergic mechanisms alone are not sufficient to influence immobility time and suggest that the cholinergic system may control, the neural circuitry upon which desipramine and nomifensine act to reduce immobility time.