It is well known that monoamine neurotransmitters: noradrenaline (NA) and serotonin (5-HT) play a key role in central nervous system (CNS) in pathophysiology of depression. The alterations in their metabolism in the brain seem to be related to the therapeutic action of antidepressants. Abnormalities with monoaminergic storage and neurotransmission are associated with a number of neurological disorders as: e.g. depression. Reserpine, used as an antihypertensive, antipsychotic drug in a low doses is a potent inhibitor of the vesicular monoamine transporter 2 (VMAT2) and acts by depleting cells of their monoamines stores. It is known that patients who took reserpine chronically began to display symptoms similar to that seen in depression. The reserpine model of depression in rat based on universally accepted monoamine hypothesis of depression and offers good predictive validity in terms of monoamine-based antidepressant activity. The aim: the present study aimed to investigate the potential antidepressant properties of an endogenous amine 1,2,3,4-tetrahydroisoquinoline (TIQ) and its possible mechanisms of action. In behavioral study, the forced swim test (FST) was used to evaluate the effects of TIQ in reserpine model of depression in rat. Additionally, the motor function of rat was checked in locomotor activity test after investigated drugs administration. Further, the content of NA, 5-HT and their metabolites, as well as the rate of metabolism in different rat brain structures were determined by HPLC methodology with ED. The reserpine model of depression was induced by chronic (14 consecutive days) administration of reserpine in a low dose (0.2 mg/kg i.p.). Results: The results from both behavioral and neurochemical studies have shown depressive-like effect of reserpine after its chronic administration. In the behavioral tests, reserpine decreased the locomotor activity (about 30% vs. control group, P<0.05) measured in actometers (Opto-Varimex activity monitors, Columbus Instruments, USA) linked on-line to a compatible IBM-PC. 14-days administration of reserpine induced also behavioral changes in FST: increase of immobility time with a simultaneous decrease of swimming activity (about 30% vs. control group). Depressive-like action of reserpine was also observed in neurochemical study by decline NA and 5-HT levels in the brain structures, mainly in the frontal cortex and striatum. TIQ (25 mg/kg i.p.) revealed antidepressant-like effect in FST and has the ability to reverse the pro-depressive effect of reserpine. In biochemical studies, TIQ completely antagonized reserpine-induced monoaminergic depression in rat brain structures. Conclusion: The obtained data indicate first, that chronically administered reserpine at a low dose leads to a good animal model of depression. Secondly, the antidepressant-like effect of TIQ based mainly on activation of monoaminergic system and antagonizing the effect of reserpine by inhibition of MAO-dependent oxidation of monoamines and increased their concentrations in the brain. Thus, in that light TIQ may be useful as a new safer and more effective compound in clinical practice for therapy of depression.
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