Promoting serotonergic neurotransmission to enhance sociability | 48784

Journal of Neuroscience and Neuropharmacology

Promoting serotonergic neurotransmission to enhance sociability

4th Global Experts Meeting on Neuropharmacology

September 14-16, 2016 San Antonio, USA

Georgianna G Gould

The University of Texas Health Science Center at San Antonio, USA

Scientific Tracks Abstracts: Neurochem Neuropharm

Abstract :

Impaired social interaction is the most prominent and drug treatment-resistant of core autism symptoms. Clinical findings and rodent studies demonstrate serotonin transmission is often disrupted in the socially-deficient brain. For example, dietary or pharmacological depletion of the 5-HT precursor tryptophan (TRP) worsens behavioral symptoms of autism in patients and impairs social interactions in mice, while TRP supplementation improved sociability in some mouse models of autistic symptoms. Also drugs such as buspirone, pargyline and vortioxetine that mimic some postsynaptic effects of serotonin are able to enhance murine social behavior within a limited dose range or time frame. The selective serotonin reuptake inhibitor (SSRIs) Prozac (fluoxetine) enhances sociability in mice. Unfortunately, however, it only does so for limited subpopulations of patients with autism. This could be because SSRI efficacy is diminished if 5-HT transporter (SERT) function is compromised by common and rare gene polymorphisms. Aside from SERT, auxilliary transporters of 5-HT in the brain include organic cation transporters (OCTs) and the plasma membrane monoamine transporter (PMAT) collectively known as â??uptake 2â?. Uptake 2 transporters remove serotonin from extracellular fluid with greater capacity but lower affinity than SERT. Our hypothesis is that if uptake 2 is blocked, impaired social behavior may improve in a broader population of individuals with autism than presently benefit from SSRI treatments. This hypothesis was tested in two socially impaired mouse models, the BTBR T+tf/J strain and SERT knockout mice. We found that blockade of uptake 2 transporters by systemically-administered pseudoisocyanine decynium-22 promoted social behavior in these mice.

Biography :

Georgianna G Gould earned her PhD in Biology in 2001 from Syracuse University, and completed Post-doctoral studies in Pharmacology at The University of Texas Health Science Center at San Antonio (UTHSCSA) under the mentorship of Dr. Alan Frazer in 2007. She was an Assistant Professor of Physiology at William Paterson University from 2007-2008. Then she joined the research faculty at UTHSCSA in 2008 to collaborate with Dr. Lyn Daws on novel drug treatments for social behavior impairments in autism. She has published more than 40 peer reviewed articles and book chapters. She involves high school and undergraduate students in her research.