On the role of serotonin 5-HT1A receptor in autistic-like behavior: cross talk of 5-HT and BDNF systems

Autism spectrum disorders (ASDs) are some of the most common neurodevelopmental disorders; however, the mechanisms underlying ASDs are still poorly understood. Serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) are known as key players in brain and behavioral plasticity and interact with each other. 5-HT1A receptor is a principal regulator of the brain 5-HT system, which modulates normal and pathological behavior. Here we investigated effects of adeno-associated-virus-based 5-HT1A receptor overexpression in the hippocam-pus of BTBR mice (which are a model of autism) on various types of behavior and on the expression of 5-HT7 receptor, proBDNF, mature BDNF, and BDNF receptors (TrkB and p75NTR). The 5-HT1A receptor overexpression in BTBR mice reduced stereotyped behavior in the marble-burying test and extended the time spent in the center in the open field test. Meanwhile, this overexpression failed to affect social behavior in the three-chambered test, immobility time in the tail suspension test, locomotor activity in the open field test, and associative learning within the "operant wall" paradigm. The 5-HT1A receptor overexpression in the hippocampus raised hippo-campal 5-HT7 receptor mRNA and protein levels. Additionally, the 5-HT1A receptor overexpression lowered both mRNA and protein levels of TrkB receptor but failed to affect proBDNF, mature BDNF, and p75NTR receptor expression in the hippocampus of BTBR mice. Thus, obtained results suggest the involvement of the 5-HT and BDNF systems' interaction mediated by 5-HT1A and TrkB receptors in the mechanisms underlying autistic-like behavior in BTBR mice.