Density and function of central serotonin (5-HT) transporters, 5-HT 1A and 5-HT2A receptors, and effects of their targeting on BTBR T+tf/J mouse social behavior

Georgianna G. Gould, Julie G. Hensler, Teresa F. Burke, Robert H. Benno, Emmanuel S. Onaivi, Lynette C. Daws

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

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 (Bmax) 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 (KD) was 2.0 ± 0.3 nM versus 1.1 ± 0.2 in C57BL/6J mice. Hippocampal 5-HT1A and 5-HT 2A receptor binding was similar among strains. However, 8-OH-DPAT-stimulated [35S] GTPγS binding in the BTBR hippocampal CA1 region was 28% higher, indicating elevated 5-HT 1A 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 D2/5-HT 2 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.

Original languageEnglish (US)
Pages (from-to)291-303
Number of pages13
JournalJournal of Neurochemistry
Volume116
Issue number2
DOIs
StatePublished - Jan 1 2011

Keywords

  • 5-HT receptor
  • CA of hippocampus
  • SERT
  • buspirone
  • fluoxetine
  • sociability

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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