title: 1,2,3,4-Tetrahydroisoquinoline produces an antidepressant-like effect in the forced swim test and chronic mild stress model of depression in the rat: Neurochemical correlates.
abstract: 1,2,3,4-Tetrahydroisoquinoline (TIQ) is an exo- and endogenous amine naturally present in mammalian brain which displays antidepressant-like effect in various animal models: the forced swim test (FST) and chronic mild stress (CMS) paradigm in rats. To elucidate this action we compared the effects of TIQ with imipramine, a classic antidepressant drug and one of the most clinically effective. Applied behavioral tests showed that TIQ produced an antidepressant-like effect with a potency comparable to that of imipramine. TIQ (25-50mg/kg i.p.), similarly to imipramine (10-30mg/kg i.p.), reduced the immobility time in FST and completely reversed the decrease in sucrose intake caused by CMS in the rat. In addition, in order to avoid the possible psychostimulating effect of TIQ we examined the influence of its administration on locomotor activity in rats. TIQ, like imipramine, produced a reduction in horizontal locomotor activity. This suggested that TIQ did not have psychostimulant properties and that prolonged swimming in the FST was a result of an increased motivation to escape from the stressful situation. The biochemical analyses have shown that TIQ activates monoaminergic systems as a reversible monoamine oxidase (MAO) inhibitor and free radical scavenger. Beyond the activation of noradrenaline and serotonin systems, TIQ also moderately affects the dopamine system. On the basis of the presented behavioral and biochemical studies we suggest that TIQ is a potential new antidepressant which may be effective for the depression therapy in a clinical setting.
authors.affiliation: Department of Neurochemistry, Institute of Pharmacology, Polish Academy of Sciences, Poland. Electronic address: mozdzen@if-pan.krakow.pl.
authors.forename: Edyta
authors.initials: E
authors.lastname: Możdżeń
authors.affiliation: Department of Pharmacology, Laboratory of Behavioral Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Smętna 12 Street, 31-343 Krakow, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Papp
authors.affiliation: Department of Pharmacology, Laboratory of Behavioral Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Smętna 12 Street, 31-343 Krakow, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Gruca
authors.affiliation: Department of Neurochemistry, Institute of Pharmacology, Polish Academy of Sciences, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wąsik
authors.affiliation: Department of Neurochemistry, Institute of Pharmacology, Polish Academy of Sciences, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Romańska
authors.affiliation: Department of Neurochemistry, Institute of Pharmacology, Polish Academy of Sciences, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Michaluk
authors.affiliation: Department of Neurochemistry, Institute of Pharmacology, Polish Academy of Sciences, Poland.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Antkiewicz-Michaluk
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D004195:Disease Models, Animal; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D013550:Swimming / Q000523:psychology; D044005:Tetrahydroisoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D044005:Tetrahydroisoquinolines
keywords: 1,2,3,4-Tetrahydroisoquinoline; Chronic mild stress; Forced swimming test; Imipramine; Metabolism of monoamines; Models of depression; Rat brain