Density and function of central serotonin (5-HT) transporters, 5-HT1A and 5-HT2A receptors, and effects of their targeting on BTBR T plus tf/J mouse social behavior

作者：Gould Georgianna G^*; Hensler Julie G; Burke Teresa F; Benno Robert H; Onaivi Emmanuel S; Daws Lynette C

来源：Journal of Neurochemistry, 2011, 116(2): 291-303.

DOI：10.1111/j.1471-4159.2010.07104.x

• 5-HT1A receptor
• buspirone
• CA(1) of hippocampus
• fluoxetine
• SERT
• sociability

P>BTBR mice are potentially useful tools for autism research because their behavior parallels core social interaction impairments and restricted-repetitive behaviors. Altered regulation of central serotonin (5-HT) neurotransmission may underlie such behavioral deficits. To test this, we compared 5-HT transporter (SERT), 5-HT1A and 5-HT2A receptor densities among BTBR and C57 strains. Autoradiographic [3H] cyanoimipramine (1nM) binding to SERT was 20-30% lower throughout the adult BTBR brain as compared to C57BL/10J mice. In hippocampal membrane homogenates, [3H] citalopram maximal binding (B-max) to SERT was 95 +/- 13 fmol/mg protein in BTBR and 171 +/- 20 fmol/mg protein in C57BL/6J mice, and the BTBR dissociation constant (K-D) was 2.0 +/- 0.3 nM versus 1.1 +/- 0.2 in C57BL/6J mice. Hippocampal 5-HT1A and 5-HT2A receptor binding was similar among strains. However, 8-OH-DPAT-stimulated [35S] GTP gamma S binding in the BTBR hippocampal CA(1) region was 28% higher, indicating elevated 5-HT1A capacity to activate G-proteins. In BTBR mice, the SERT blocker, fluoxetine (10 mg/kg) and the 5-HT1A receptor partial-agonist, buspirone (2 mg/kg) enhanced social interactions. The D-2/5-HT2 receptor antagonist, risperidone (0.1 mg/kg) reduced marble burying, but failed to improve sociability. Overall, altered SERT and/or 5-HT1A functionality in hippocampus could contribute to the relatively low sociability of BTBR mice.

• 出版日期2011-1