CHRONIC IMIPRAMINE TREATMENT-INDUCED CHANGES IN ACETYLCHOLINESTERASE (EC-3.1.1.7) ACTIVITY IN DISCRETE RAT-BRAIN REGIONS

Cholinergic as well as monoaminergic neurotransmission seems to be inv olved in the etiology of affective disorders. Chronic treatment with i mipramine, a classical antidepressant drug, induces adaptive changes i n monoaminergic neurotransmission. In order to identify possible chang es in cholinergic neurotransmission we measured total, membrane-bound and soluble acetylcholinesterase (Achase) activity in several rat brai n regions after chronic imipramine treatment. Changes in Achase activi ty would indicate alterations in acetylcholine (Ach) availability to b ind to its receptors in the synaptic cleft. Male rats were treated wit h imipramine (20 mg/kg, ip) for 21 days, once a day. Twenty-four hours after the last dose the rats were sacrificed and homogenates from sev eral brain regions were prepared. Membrane-bound Achase activity (nmol thiocholine formed min(-1) mg protein(-1)) after chronic imipramine t reatment was significantly decreased in the hippocampus (control = 188 .8 +/- 19.4, imipramine = 154.4 +/- 7.5, P<0.005) and striatum (contro l = 850.9 +/- 59.6, imipramine = 742.5 +/- 34.7, P<0.005). A small inc rease in total Achase activity was observed in the medulla oblongata a nd pens. No changes in enzyme activity were detected in the thalamus o r total cerebral cortex. Since the levels of Achase seem to be enhance d through the interaction between Ach and its receptors, a decrease in Achase activity may indicate decreased Ach release by the nerve endin gs. Therefore, our data indicate that cholinergic neurotransmission is decreased after chronic imipramine treatment which is consistent with the idea of an interaction between monoaminergic and cholinergic neur otransmission in the antidepressant effect of imipramine.