On Associations between Fear-Induced Aggression, Transcripts, and Serotonin Receptors in the Brains of Norway Rats: An Influence of Antiaggressive Drug TC-2153.

The (brain-derived neurotrophic factor) gene contains eight regulatory exons (I-VIII) alternatively spliced to the protein-coding exon IX. Only exons I, II, IV, and VI are relatively well studied. The BDNF system and brain serotonergic system are tightly interconnected and associated with aggression. The benzopentathiepine TC-2153 affects both systems and exerts antiaggressive action. Our aim was to evaluate the effects of TC-2153 on the exons I-IX's expressions and serotonin receptors' mRNA levels in the brain of rats featuring high aggression toward humans (aggressive) or its absence (tame). Aggressive and tame adult male rats were treated once with vehicle or 10 or 20 mg/kg of TC-2153. mRNA was quantified in the cortex, hippocampus, hypothalamus, and midbrain with real-time PCR. Selective breeding for high aggression or its absence affected the serotonin receptors' and exons' transcripts differentially, depending on the genotype (strain) and brain region. TC-2153 had comprehensive effects on the exons' expressions. The main trend was downregulation in the hypothalamus and midbrain. TC-2153 increased 5-HT receptor hypothalamusc mRNA expression. For the first time, an influence of TC-2153 on the expressions of regulatory exons and the 5-HT receptor was shown, as was an association between regulatory exons and fear-induced aggression involving genetic predisposition.