<Emphasis Type="Italic">Kalrn</Emphasis> promoter usage and isoform expression respond to chronic cocaine exposure |
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Authors: | Richard E Mains Drew D Kiraly Jodi E Eipper-Mains Xin-Ming Ma Betty A Eipper |
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Institution: | (1) Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030-3401, USA;(2) Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030-3401, USA |
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Abstract: | Background The long-term effects of cocaine on behavior are accompanied by structural changes in excitatory glutamatergic synapses onto
the medium spiny neurons of the striatum. The Kalrn gene encodes several functionally distinct isoforms; these multidomain guanine nucleotide exchange factors (GEFs) contain
additional domains known to interact with phosphatidylinositides as well as with a number of different proteins. Through their
activation of Rho proteins and their interactions with other proteins, the different Kalirin isoforms affect cytoskeletal
organization. Chronic exposure of adult male rodents to cocaine increases levels of Kalirin 7 in the striatum. When exposed
chronically to cocaine, mice lacking Kalirin 7, the major adult isoform, fail to show an increase in dendritic spine density
in the nucleus accumbens, show diminished place preference for cocaine, and exhibit increased locomotor activity in response
to cocaine. |
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Keywords: | |
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