Effect of Central Administration of Brain-Derived Neurotrophic Factor (BDNF) on Behavior and Brain Monoamine Metabolism in New Recombinant Mouse Lines Differing by 5-HT 1A Receptor Functionality

• Published in: International journal of molecular sciences Vol. 22; no. 21
• Main Authors: Bazovkina, Darya, Naumenko, Vladimir, Bazhenova, Ekaterina, Kondaurova, Elena
• Format: Journal Article
• Language: English
• Published: Switzerland 05-11-2021
• Subjects: Aggression - drug effects; Animals; Behavior, Animal - drug effects; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain-Derived Neurotrophic Factor - pharmacology; Disease Models, Animal; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Receptor, Serotonin, 5-HT1A - genetics; Receptor, Serotonin, 5-HT1A - metabolism; Serotonin - metabolism; recombinant mouse lines; BDNF; brain serotonin system; brain dopamine system; 5-HT1A and 5-HT2A receptors functional activity; aggression; HPLC
• ISSN: 1422-0067

Experiments were carried out on recombinant B6.CBA-D13Mit76C (B6-M76C) and B6.CBA-D13Mit76B (B6-M76B) mouse lines created by transferring a 102.73-118.83 Mbp fragment of chromosome 13, containing the 5-HT
receptor gene, from CBA or C57BL/6 strains to a C57BL/6 genetic background, correspondingly. We have recently shown different levels of 5-HT1A receptor functionality in these mouse lines. The administration of BDNF (300 ng/mouse, i.c.v.) increased the levels of exploratory activity and intermale aggression only in B6-M76B mice, without affecting depressive-like behavior in both lines. In B6-M76B mice the behavioral alterations were accompanied by a decrease in the 5-HT
receptor functional activity and the augmentation of levels of serotonin and its main metabolite, 5-HIAA (5-hydroxyindoleacetic acid), in the midbrain. Moreover, the levels of dopamine and its main metabolites, HVA (homovanillic acid) and DOPAC (3,4-dihydroxyphenylacetic acid), were also elevated in the striatum of B6-M76B mice after BDNF treatment. In B6-M76C mice, central BDNF administration led only to a reduction in the functional activity of the 5-HT
receptor and a rise in DOPAC levels in the midbrain. The obtained data suggest the importance of the 102.73-118.83 Mbp fragment of mouse chromosome 13, which contains the 5-HT
receptor gene, for BDNF-induced alterations in behavior and the brain monoamine system.