Long-term administration of atropine, imipramine, and viloxazine alters responsiveness of rat cortical neurones to acetylcholine.

Rats were treated daily with atropine (2.5 mg/kg), imipramine (5 mg/kg), viloxazine (5 mg/kg), or saline for 14 days. Thirty-six hours following the final injection the rats were anaesthetized with urethane and the sensitivity of neurones in the somatosensory cortex to iontophoretically applied acetylcholine (ACh) was determined. In saline-treated animals the large majority of neurones was excited by ACh with depression being observed infrequently. This was reversed in drug-treated animals, the predominant response to iontophoretic ACh becoming one of depression. The results indicate that long-term administration of antidepressant drugs may induce qualitative changes in the sensitivity of central cholinergic systems.