title: Antidepressant-like effect of 1,2,3,4-tetrahydroisoquinoline and its methyl derivative in animal models of depression.
abstract: BACKGROUND
  Most of the currently used antidepressant drugs are monoamine-based compounds, acting by the inhibition of re-uptake or metabolism of noradrenaline (NA) and/or serotonin (5-HT), because these neurotransmitters play a key role in the pathophysiology of depression. The aim of this study was to investigate the potential antidepressant-like activity of an endogenous amine, 1,2,3,4-tetrahydroisoquinoline (TIQ) and its close derivative, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ).
  
  
  METHODS
  The experiments were carried out on male C57BL6J mice. The antidepressant-like activity of TIQs was evaluated in the behavioral tests: the forced swim test (FST) and tail suspension test (TST) and neurochemical analysis. TIQ and 1MeTIQ were administrated in three differences doses of 10, 25 or 50mg/kg. Imipramine (IMI; 15 or 30mg/kg) was used as a reference drug. In the neurochemical ex vivo study, the levels of NA, 5-HT and their metabolites, the rate of monoamine metabolism and their neuronal activity in different mouse brain structures were determined by HPLC with electrochemical detection.
  
  
  RESULTS
  The results of this study have demonstrated that TIQ and 1MeTIQ produced antidepressant-like effect in the FST and TST because they significantly decreased the immobility time comparably to IMI. Biochemical data have demonstrated that administration of TIQs led to the activation of NA and 5-HT systems.
  
  
  CONCLUSIONS
  The results reported in this paper indicate that TIQ and 1MeTIQ possess a distinct antidepressant activity. In the light of these findings, we suggest that both tested compounds may be effective for the depression therapy in a clinical setting with better tolerance of side effects.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Neurochemistry, Kraków, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Możdżeń
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Neurochemistry, Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wąsik
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Neurochemistry, Kraków, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Romańska
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Neurochemistry, Kraków, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Michaluk
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Neurochemistry, Kraków, Poland. Electronic address: antkiew@if-pan.krakow.pl.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Antkiewicz-Michaluk
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003863:Depression / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019417:Hindlimb Suspension; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013550:Swimming; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D044005:Tetrahydroisoquinolines; C050386:1-methyl-1,2,3,4-tetrahydroisoquinoline; C014843:1,2,3,4-tetrahydroisoquinoline; D007099:Imipramine
keywords: Depression; Forced swim test; Metabolism of monoamines; TIQs; Tail suspension test