Chronic imipramine treatment-induced changes in acetylcholinesterase (EC 3.1.1.7) activity in discrete rat brain regions

Abstract

Cholinergic as well as monoaminergic neurotransmission seems to be involved in the etiology of affective disorders. Chronic treatment with imipramine, a classical antidepressant drug, induces adaptive changes in monoaminergic neurotransmission. In order to identify possible changes in cholinergic neurotransmission we measured total, membrane-bound and soluble acetylcholinesterase (Achase) activity in several rat brain regions after chronic imipramine treatment. Changes in Achase activity would indicate alterations in acetylcholine (Ach) availability to bind to its receptors in the synaptic cleft. Male rats were treated with 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 several brain regions were prepared. Membranebound Achase activity (nmol thiocholine formed min -1 mg protein -1 ) after chronic imipramine treatment was significantly decreased in the hippocampus (control = 188.8 ± 19.4, imipramine = 154.4 ± 7.5, P<0.005) and striatum (control = 850.9 ± 59.6, imipramine = 742.5 ± 34.7, P<0.005). A small increase in total Achase activity was observed in the medulla oblongata and pons. No changes in enzyme activity were detected in the thalamus or total cerebral cortex. Since the levels of Achase seem to be enhanced through the interaction between Ach and its receptors, a decrease in Achase activity may indicate decreased Ach release by the nerve endings. 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 neurotransmission in the antidepressant effect of imipramine.

Effects of administration of sertraline, clozapine, amitriptyline and imipramine on brain serotonin, liver enzymes and blood chemistry of rabbit

“…Other behavioural signs observed in the rabbits, include dry nose and mouth, photosensitivity, frequent urination and disorientation. This observation is in agreement with previous reports of Karolewick et al (1996), Camarini and Benedito (1997) and Ebuehi et al (2004aEbuehi et al ( , 2004b. The intraperitoneal administration of amitriptyline and imipramine increased the body weights of rabbits.…”

“…Sertraline and clozapine belong to antidepressant and antipsychotic drugs respectively, while imipramine and amitriptyline are tricyclic antidepressants. Biochemical studies on imipramine demonstrated that this drug increased the activity of monoamine neurotransmitters, norepinephrine and serotonin by inhibiting their reuptake into neurons (Barker et al, 1992;Camarini and Benedito, 1997;Cantrell et al, 1999). Sertraline is an oral antidepressant drug of the selective serotonin reuptake type.…”

Efficacy of Tricyclic Antidepressant Therapy in Adults With Cyclic Vomiting Syndrome

“…20,21 Although the exact etiology of CVS is unknown, it could be possible that this area of the brain is activated by the various factors or ''triggers'' of CVS leading to manifestation of the vomiting symptoms. Animal studies show that chronic TCA therapy decreases cholinergic neurotransmission in the medulla, 22 selectively modulates the a-2 adrenoreceptors in the nucleus tractus solitarius and reduces the splanchnic sympathetic nervous system discharge by increasing a-2 adrenoreceptor discharge in the rostral ventral medulla. 23 Thus, TCA agents could have effects in these areas of the central nervous system in humans and modify the brain-gut axis and also autonomic dysfunction, 1,24 a possible underlying mechanism for cycles of CVS.…”

Effects of Imipramine Treatment on δ-Opioid Receptors of the Rat Brain Cortex and Striatum

“…The controls in each group were intraperitoneally injected with 0.5 ml saline, and the experimental rats were given 0.5 ml imipramine hydrochloride (30 mg/kg body wt./day in subacute treatment; 20 mg/kg body wt./day in chronic treatment). These doses and time of administration are usually employed to carry out studies on the mechanism of the action of imipramine [8,9,10]. The animals received the daily dose in one administration.…”