Work

Deletion of Go2α abolishes cocaine‐induced behavioral sensitization by disturbing the striatal dopamine system

Year: 2008

Type: article

Abstract: The α‐subunits of the trimeric Go class of GTPases, comprising the splice variants Golα and Go2α, are abundantly expressed in brain and reside on both plasma membrane and synaptic vesicles. Go2α is involved in the vesicular storage of monoamines but its physiological relevance is still obscure. We now show that genetic depletion of Go2α reduces motor activity induced by dopamine‐enhancing drugs like cocaine, as repeated injections of cocaine fail to provoke behavioral sensitization in Go2α −/− mice. In Go2α −/− mice, D1 receptor signaling in the striatum is attenuated due to a reduced expression of Golfα and Gsα. Following cocaine treatment, Go2α −/− mice have lower D1 and higher D2 receptor amounts compared to wild‐type mice. The lack of behavioral sensitization correlates with reduced dopamine levels in the striatum and decreased expression of tyrosine hydroxylase. One reason for the neurochemical changes may be a re‐duced uptake of monoamines by synaptic vesicles from Go2α −/− mice as a consequence of a lowered set point for filling. We conclude that Go2α optimizes vesicular filling which is instrumental for normal dopamine functioning and for the development of drug‐induced behavioral sensitization.—Brunk, I., Blex, C., Sanchis‐ Segura, C., Sternberg, J., Perreau‐Lenz, S., Bilbao, A., Hörtnagl, H., Baron, J., Juranek, J., Laube, G., Birnbaumer, L., Spanagel, R., Ahnert‐Hilger, G. Deletion of Go2α abolishes cocaine‐induced behavioral sensitization by disturbing the striatal dopamine system. FASEB J. 22, 3736–3746 (2008)

Source: The FASEB Journal

DOI: 10.1096/fj.08-111245