title: Antidepressant-Like Effect of the Endogenous Neuroprotective Amine, 1MeTIQ in Clonidine-Induced Depression: Behavioral and Neurochemical Studies in Rats.
abstract: Biogenic amines such as norepinephrine, dopamine, and serotonin play a well-described role in the treatment of mood disorders especially depression. Animal models are widely used to study antidepressant-like effect in rodents; however, it should be taken into account that pharmacological models do not always answer to the complexity of the disease processes. This study verified the behavioral (forced swim test (FST), locomotor activity test) and neurochemical effects (monoamines metabolism) of a low dose of clonidine (0.1 mg/kg i.p.) which was used as an experimental model of depression. In such pharmacological model, we investigated the antidepressant-like effect of an endogenous neuroprotective amine, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) administered in a dose of 25 mg/kg (i.p.) before clonidine in the behavioral and neurochemical tests carried out in rats. The behavioral study has shown that clonidine produced depression in the locomotor activity test but did not cause pro-depressive effect in the FST. 1MeTIQ produced antidepressant-like effect in the FST and completely antagonized clonidine-induced sedation in the locomotor activity test. Neurochemical data demonstrated that clonidine produced a significant inhibition of monoamine metabolism in the central nervous system. The release of dopamine, noradrenaline, and serotonin as well as the rate of their metabolism were diminished in the investigated brain structures (frontal cortex, hypothalamus, and striatum). 1MeTIQ completely antagonized the clonidine-induced depression of monoaminergic systems and restored their levels to the control values. 1MeTIQ as an endogenous neuroprotective compound with a distinct antidepressant-like activity in rodents produces hope on the efficiency of antidepressant medicines for future practical clinical use.
authors.affiliation: Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland. antkiew@if-pan.krakow.pl.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Antkiewicz-Michaluk
authors.affiliation: Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Romańska
authors.affiliation: Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wąsik
authors.affiliation: Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Michaluk
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry; D003000:Clonidine / Q000633:toxicity*; D003863:Depression / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D006719:Homovanillic Acid / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming / Q000523:psychology; D013565:Sympatholytics / Q000633:toxicity*; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*
chemical_list: D015306:Biogenic Monoamines; D018696:Neuroprotective Agents; D013565:Sympatholytics; D044005:Tetrahydroisoquinolines; D015102:3,4-Dihydroxyphenylacetic Acid; C050386:1-methyl-1,2,3,4-tetrahydroisoquinoline; D003000:Clonidine; D006719:Homovanillic Acid
keywords: Brain structures; Clonidine model of depression; Forced swim test; HPLC; Metabolism of monoamines; Rat