Lankapulle Jayanthi, Ph.D.
Assistant Professor, MUSC

Contact Information:
jayanthi@musc.edu

843.792.8543
843.792.9884

Education:

BSc (BS), Chemistry, Physics and Zoology, 1980-1983, University of Madras, Madras, India
MSc (MS), Biochemistry, 1983-1985, Sri Venkateswara University, Tirupati, India
PhD, Biochemistry, 1986-1992, Christian Medical College Hospital, Vellore, India

Project Discription:

In Vivo Regulation of the Norepinephrine Transporter by Cocaine.

Cocaine use during pregnancy is associated with long-lasting neurobehavioral abnormalities in the progeny such as deficits in attention and short-term memory. Altered attention and stress responses in the progeny are linked to psychostimulant action on neuronal norepinephrine transporter (NET). Our goal is to understand the mechanisms involved in the functional regulation of NET contributing to amine transporter dysfunction in drug addiction. With support from the pilot project from Neurobiology of Addiction Center (NARC), the implications of in utero cocaine exposure on the functional expression of NET was investigated to relate transporter changes to behavioral alterations in the offspring. Subcutaneous administration of cocaine (30 mg/kg body wt) to pregnant rats from gestation period E8 to E20 resulted in an elevated NE transport in the placental membrane vesicles compared to saline administered controls which is reflected in increased NET protein levels. There was no significant change in the weight gain of the pregnant rats (dams) between cocaine and saline groups suggesting no drastic side effects due to cocaine injections. There was also no significant change in the number or the weight of pups between cocaine and saline injected rats at the time of birth. In the maternal brain, cocaine administration produced region specific alterations in synaptosomal NE uptake of the monoamines. While NET function was elevated in the striatum and cerebellum, function was reduced in the cortex. There was a significant increase in NE uptake by synaptosomes prepared from all three specific brain regions (striatum, cortex and cerebellum) in in utero cocaine exposed pups when allowed to reach adulthood (16 weeks) without further cocaine exposure suggesting a long-lasting alterations in the NET expression in the progeny. When tested for spontaneous activity, cocaine exposed offspring were more active (total and horizontal) compared to controls (offspring from saline exposed dams). These results suggest that altered monoamine transport function in in utero cocaine exposed offspring is long-lasting and may be the underlying cause for observed behavioral changes. The support from NARC pilot project enabled us obtain the above preliminary data. Further investigations are underway to obtain more data in support of writing a manuscript. A grant application will be submitted to NIH based on these data seeking long-term extramural funding.