Novel Therapeutic Targets to Treat Social Behavior Deficits in Autism and Related Disorders
Annual rept. 30 Sep 2012-11 Sep 2013
TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO
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The project goal is to test the potential of organic cation transporter OCT blockade to improve social behavior in inbred mice exhibiting low sociability, specifically BTBRTtfJ, and 129S1SvImJ strains. OCT blockade is also being examined in sociable C57BL6 and DBA1J mice. The OCT blocker decynium-22 D-22 is compared in efficacy to the serotonin reuptake inhibitor fluoxetine, and the antipsychotic risperidone. The latter two are commonly used to treat autism symptoms, but do little to improve social behavior. Experiments assessing D-22 pharmacokinetics in mouse brain and serum were performed for specific aim 1 analysis of samples is still underway. However, D-22 injected systemically can enter the brain, and has a clearance half-life of approximately 30-40 min. Blockade of 3H serotonin uptake in synaptosomes revealed that D-22 is effective at nanomolar concentrations, and works independently of fluoxetine for aim 2. Chronoamperometry to compare serotonin uptake rates was performed in vivo at micromolar concentrations, and clearance was most rapid in BTBR mice. Finally, behavioral studies of the effects of D-22, risperidone and fluoxetine on sociability, social dominance, and marble burying tests are underway for aim 3. Preliminary findings indicate that D-22 can enhance social behavior, and that sociability testing increases serum corticosterone levels.
- Biological and Medical Sciences
- Medicine and Medical Research