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1,2,3,4-Tetrahydroisoquinoline as the potential antidepressant compound in forced swimming test in rat
Authors:Edyta Mo?d?eń  Agnieszka W?sik  Jerzy Michaluk  Irena Romańska  Lucyna Antkiewicz-Michaluk
Institution:Department of Neurochemistry, Institute of Pharmacology, Polish Academy of Sciences, Sm?tna 12, PL 31-343 Kraków, Poland
Abstract:1,2,3,4-Tetrahydroisoquinoline (TIQ) is an exo- and endogenous amine present naturally in mammalian brain and may be the natural regulator of monoaminergic systems with a visible neuroprotective potency Antkiewicz-Michaluk et al., J Neurochem, 2006]. In our study we tested the potential antidepressant properties of TIQ in comparison with a classic antidepressant drug, imipramine by using forced swimming test in rats (FST). Further, we measured the levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT), and their metabolites, as well as the rate of monoamines metabolism in different rats brain structures by HPLC methodology with ED. The locomotor activity test was used to check motor function of rat after investigated drugs administration. All experiments were performed on male Wistar rats weighing 220 –240 g.ResultsFST has shown that TIQ (10 , 25 , 50 mg/kg, ip) significantly reduced immobility time similarly to imipramine (30 mg/kg, ip). TIQ significantly elevated swimming activity (p < 0.01) while imipramine increased climbing time (p < 0.01). Additionally, TIQ (25 mg/kg, ip) and imipramine (15 mg/kg, ip) injected simultaneously decreased immobility time, increased the swimming and did not affect the climbing activity. The biochemical analysis showed that TIQ increased the levels of monoamines: DA, NA and 5-HT in rat brain structures. Moreover, the factor of DA re-uptake inhibition, calculated as the ratio 3-MT]/DOPAC], was significantly elevated by TIQ administration. The rate of serotonin metabolism was strongly decreased (p < 0.01) while, the rate of noradrenaline metabolism was increased (p < 0.05) after injection of TIQ and imipramine. TIQ did not change the locomotor activity in rats.ConclusionsThe obtained data indicate that TIQ produced antidepressant-like effect in FST with potency comparable to imipramine. Thus, in that light and taking into account its neuroprotective potential of action in the brain TIQ may be useful in clinical practice for therapy of depression.
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