Abused drugs produce long-lasting changes in behaviors via biochemical mechanisms that are largely unknown. Drug-altered changes in expression of specific genes in the brain can provide a major window on possible biochemical substrates for addiction. To further explore this area, we have established and developed subtracted differential display and array hybridization techniques that have allowed identification of dozens of distinct cDNAs that correspond to candidate drug-regulated genes expressed in brain. During this FY, we have enhanced characterization of candidate genes whose expression is regulated by amphetamine, cocaine and morphine. Sequence analyses of one of these cDNAs revealed novel splice variant isoforms of a cell adhesion gene family member, NrCAM. Studies of this gene's expression reveal that it is a good candidate to contribute to altered synaptic connectivities that could play roles in the complex neuroadaptive processes characteristic of addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Intramural Research (Z01)
Project #
1Z01DA000157-04
Application #
6103868
Study Section
Special Emphasis Panel (MNRB)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Ishiguro, Hiroki; Liu, Qing-Rong; Gong, Jian-Ping et al. (2006) NrCAM in addiction vulnerability: positional cloning, drug-regulation, haplotype-specific expression, and altered drug reward in knockout mice. Neuropsychopharmacology 31:572-84
Gong, J-P; Liu, Q-R; Zhang, P-W et al. (2005) Mouse brain localization of the protein kinase C-enhanced phosphatase 1 inhibitor KEPI (kinase C-enhanced PP1 inhibitor). Neuroscience 132:713-27
Liu, Qing-Rong; Gong, Jian-Ping; Uhl, George R (2005) Families of protein phosphatase 1 modulators activated by protein kinases a and C: focus on brain. Prog Nucleic Acid Res Mol Biol 79:371-404
Liu, Qing-Rong; Zhang, Ping-Wu; Lin, Zhicheng et al. (2004) GBPI, a novel gastrointestinal- and brain-specific PP1-inhibitory protein, is activated by PKC and inactivated by PKA. Biochem J 377:171-81
Sokolov, Boris P; Polesskaya, Oxana O; Uhl, George R (2003) Mouse brain gene expression changes after acute and chronic amphetamine. J Neurochem 84:244-52
Kitanaka, Nobue; Kitanaka, Junichi; Walther, Donna et al. (2003) Comparative inter-strain sequence analysis of the putative regulatory region of murine psychostimulant-regulated gene GNB1 (G protein beta 1 subunit gene). DNA Seq 14:257-63
Kitanaka, Junichi; Kitanaka, Nobue; Takemura, Motohiko et al. (2002) Isolation and sequencing of a putative promoter region of the murine G protein beta 1 subunit (GNB1) gene. DNA Seq 13:39-45
Liu, Qing-Rong; Zhang, Ping-Wu; Zhen, Qiaoxi et al. (2002) KEPI, a PKC-dependent protein phosphatase 1 inhibitor regulated by morphine. J Biol Chem 277:13312-20