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

Details

• Personal Author:
  Benno RH ; Burke TF ; Daws LC ; Gould GG ; Hensler JG ; Onaivi ES
• Description:
  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-HT(1A) and 5-HT(2A) receptor densities among BTBR and C57 strains. Autoradiographic [(3) H] cyanoimipramine (1 nM) binding to SERT was 20-30% lower throughout the adult BTBR brain as compared to C57BL/10J mice. In hippocampal membrane homogenates, [(3) H] 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-HT(1A) and 5-HT(2A) receptor binding was similar among strains. However, 8-OH-DPAT-stimulated [(35) S] GTPgammaS binding in the BTBR hippocampal CA(1) 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-HT(1A) receptor partial-agonist, buspirone (2 mg/kg) enhanced social interactions. The D(2) /5-HT(2) receptor antagonist, risperidone (0.1 mg/kg) reduced marble burying, but failed to improve sociability. Overall, altered SERT and/or 5-HT(1A) functionality in hippocampus could contribute to the relatively low sociability of BTBR mice. [Description provided by NIOSH]
• Subjects:
  Animals Behavior Laboratories Nervous System Occupational Health Safety
• Keywords:
  Animal-studies Author Keywords: 5-HT1A Receptor Behavioral-tests Buspirone CA1 Of Hippocampus Fluoxetine Laboratory-animals Laboratory-testing Neurological-reactions Neurological-system SERT Sociability Sociological-factors Statistical-analysis

  More +
• ISSN:
  0022-3042
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 6 ; Texas
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  291-303
• Volume:
  116
• Issue:
  2
• NIOSHTIC Number:
  nn:20038154
• Citation:
  J Neurochem 2011 Jan; 116(2):291-303
• Contact Point Address:
  Georgianna G. Gould, Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900
• Email:
  gouldg@uthscsa.edu
• Federal Fiscal Year:
  2011
• Performing Organization:
  University of Texas Health Science Center, Houston
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Journal of Neurochemistry
• End Date:
  20250630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c23f9a86b51f045081aa3cc0e8631523b892d99666a76648d314411f5ae5c83ab054da91247f626d7987d6ca46073c3237bf1f511fcc9cef0335adafdf1bff07
• Download URL:
  https://stacks.cdc.gov/view/cdc/191951/cdc_191951_DS1.pdf
• File Type:
  [PDF - 478.44 KB ]