[Effect of new potential psychotropic drug, 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride, on the expression of serotonin-related genes in mouse brain]

Mol Biol (Mosk). 2011 Mar-Apr;45(2):282-8.
[Article in Russian]

Abstract

Study of molecular mechanisms of psychotropic drug action is the main aim of molecular psychopharmacology. New synthetic analog of variacin 8-(Trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine (TX-2153) was shown to produce anxiolytic and anticonvulsant effects on mice. Here the effect of chronic administration of TX-2153 on expression of some serotonin-related genes in mouse brain was investigated. The drug (10 mg/kg, per os, 16 days) was administered to adult males of ASC (Antidepressant Sensitive Catalepsy) mouse strain characterizing by alterations in behavior and brain serotonin system. The expression of genes encoding 1) the key enzyme of serotonin synthesis, tryptophan hydroxylase 2 (TPH2), 2) main enzyme of serotonin degradation, monoamine oxydase A (MAOA), 3) 5-HT transporter (SERT) and 4) 5-HT(1A) receptor was studied using quantitative RT-PCR. TX-2153 significantly reduced m-RNA level of 5-HT(1A) receptor and MAOA genes in the midbrain without any effect on expression of these genes in the frontal cortex and hippocampus. The drug failed to affect expression of TPH2 and SERT genes in the midbrain. The result indicates involvement of the brain 5-HT system in the molecular mechanism underlying the effect of TX-2153.

Publication types

  • English Abstract

MeSH terms

  • Animals
  • Bacteriocins / pharmacology
  • Benzothiepins / pharmacology*
  • Brain / drug effects
  • Brain / metabolism
  • Disease Models, Animal
  • Gene Expression / drug effects
  • Gene Expression Regulation
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Male
  • Mesencephalon / drug effects*
  • Mesencephalon / metabolism
  • Mice
  • Monoamine Oxidase / drug effects
  • Monoamine Oxidase / genetics
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Psychotropic Drugs / pharmacology*
  • Receptor, Serotonin, 5-HT1A / genetics
  • Serotonin / genetics*
  • Serotonin / metabolism
  • Serotonin 5-HT1 Receptor Antagonists / pharmacology*
  • Serotonin Plasma Membrane Transport Proteins / drug effects
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Tryptophan Hydroxylase / drug effects
  • Tryptophan Hydroxylase / genetics

Substances

  • 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine
  • Bacteriocins
  • Benzothiepins
  • Monoamine Oxidase Inhibitors
  • Psychotropic Drugs
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, mouse
  • variacin
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • Tph2 protein, mouse
  • Tryptophan Hydroxylase
  • Monoamine Oxidase