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.

Repeated Transcranial Direct Current Stimulation Induces Behavioral, Metabolic and Neurochemical Effects in Rats on High-Calorie Diet

“…Following each measurement, (in our conditions the time of the distribution of all investigated parameters was about 25 min) additional 10 min period was left wherein the base-line recuperates. DA and 5-HT and their metabolites were quantified by peak area comparisons with standards run on the day of analysis (ChemStation, Hewlett-Packard software computer program) (Antkiewicz-Michaluk et al, 2017 ).…”

“…L and Ob groups (intact) were compared with Student T-test. The density (B max ) and affinity (K D ) of dopamine D1 and D2 receptors were calculated by nonlinear regression (Scatchard analysis, Statistics Computer Program) (Antkiewicz-Michaluk et al, 2017 ).…”

“…Analogously, the rate of serotonin metabolism was expressed as the ratio: [5-HIAA]/[5-HT] × 100 . The indices were calculated using concentrations from individual tissue samples (Antkiewicz-Michaluk et al, 2017 ).…”

1metiq, an Endogenous Compound Present in the Mammalian Brain Displays Neuroprotective, Antiaddictive and Antidepressant-Like Activity in Animal Models of theCentral Nervous System Disorders

“…In all of the above introduced animal models of depression, both investigated compounds (TIQ and 1MeTIQ) completely antagonized behavioral and neurochemical syndromes of depressive-like behavior in rodents displaying therapeutic potential similar to a classical antidepressant, imipramine [59,88,89].…”

Study of Sex Differences in Duloxetine Efficacy for Depression in Transgenic Mouse Models

“…During the past decades, dopamine (DA), norepinephrine (NE) and serotonin (5-HT) have been the major targets of antidepressants (Zocchi et al, 2003 ; Elhwuegi, 2004 ; Andrews et al, 2015 ). For example, reduction of monoaminergic function has been improved by anti-depressant treatment, suggesting a connection between modified monoamine metabolism and depression (Papakostas et al, 2007 ; Antkiewicz-Michaluk et al, 2017 ). The two major classes of antidepressants used to treat MDD are the selective serotonin reuptake inhibitors (SSRIs), and serotonin–norepinephrine reuptake inhibitors (SNRIs; Linde et al, 2015 ).…”