EFFECT OF BRAIN-DERIVED NEUROTROPHIC FACTOR ON BEHAVIOR AND KEY MEMBERS OF THE BRAIN SEROTONIN SYSTEM IN GENETICALLY PREDISPOSED TO BEHAVIORAL DISORDERS MOUSE STRAINS

摘要

The effect of brain-derived neurotrophic factor (BDNF) on depressive-like behavior and serotonin (5-HT) system in the brain of antidepressant sensitive cataleptics (ASC)/lcg mouse strain, characterized by depressive-like behavior, in comparison with the parental nondepressive CBA/Lac mouse strain was examined.Significant decrease of catalepsy and tail suspension test (TST) immobility was shown 17 days after acute central BDNF administration (300 ng i.c.v.) in ASC mice.In CBA mouse strain, BDNF moderately decreased catalepsy without any effect on TST immobility time.Significant difference between ASC and CBA mice in the effect of BDNF on 5-HT system was revealed.It was shown that central administration of BDNF led to increase of 5-HT_(1A) receptor gene expression but not 5-HT_(1A) functional activity in ASC mice.Increased tryptophan hydroxylase-2 (Tph-2) and 5-HT_(2A) receptor genes expression accompanied by 5-HT_(2A) receptor sensitization was shown in BDNF-treated ASC but not in CBA mouse strain, suggesting BDNF-induced increase of the brain 5-HT system functional activity and activation of neurogenesis in "depressive" ASC mice.There were no changes found in the 5-HT transporter mRNA level in BDNF-treated ASC and CBA mice.In conclusion, central administration of BDNF produced prolonged ameliorative effect on depressive-like behavior accompanied by increase of the Tph-2, 5-HT_(1A) and 5-HT_(2A) genes expression and 5-HT_(2A) receptor functional activity in animal model of hereditary behavior disorders.