There are large individual differences among humans and animals in behavioral, physiological and toxicological responses to drugs of abuse. Many of these individual differences in behavioral responses to drugs display substantial genetic components. Transgenic animals provide means for approaching several interrelated goals: 1)Ascertainment of biochemical and behavioral consequences of the introduction of or disruption of specific genes;2)Ascertainment of the consequences of over- or under-expressing candidate genes identified in human studies;3) Elucidation of gene elements yielding cell-type specific expression and trans-synaptic gene regulation;4) Studying influences of interactions between variants at different genomic loci;5)Elucidating haplotype-specific levels of expression differences in vivo, expecially when currently-available cultured cell models are not optimal. Influences of human allelic variations and interactions between dopamine and other systems in mechanisms of reward, reinforcement and learning have led to continuing focus on these systems during this year. In continuing studies of combined transporter and transporter/receptor knockouts, we have obtained novel data concerning the relationship between expression of each of these gene products at normal levels and drug-induced behavioral changes. In studies of variations at candidate gene loci determined from studies of drug-regulated gene expression, we have identified possible effects of cocaine reward in mice with altered levels of expression of KEPI. We have characterized mice with deletions of an orphan transporter vt-3 and identified its role in uptake of proline and leucine in brain synaptosomes, as well as the ability of other uptake systems to compensate for any effects of its constutuitive deletion on a variety of behaviors. In other single gene knockout experiments, we have reported effects of transporter and receptor deletions on reward and depression related phenotypes.

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National Institute on Drug Abuse
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Musci, Rashelle J; Masyn, Katherine E; Benke, Kelly et al. (2016) The effects of the interplay of genetics and early environmental risk on the course of internalizing symptoms from late childhood through adolescence. Dev Psychopathol 28:225-37
Drgonova, Jana; Walther, Donna; Wang, Katherine J et al. (2015) Mouse Model for Protein Tyrosine Phosphatase D (PTPRD) Associations with Restless Leg Syndrome or Willis-Ekbom Disease and Addiction: Reduced Expression Alters Locomotion, Sleep Behaviors and Cocaine-Conditioned Place Preference. Mol Med 21:717-725
Takamatsu, Y; Hagino, Y; Sato, A et al. (2015) Improvement of learning and increase in dopamine level in the frontal cortex by methylphenidate in mice lacking dopamine transporter. Curr Mol Med 15:245-52
Kasahara, Y; Arime, Y; Hall, F S et al. (2015) Region-specific dendritic spine loss of pyramidal neurons in dopamine transporter knockout mice. Curr Mol Med 15:237-44
Sasaki, Kazumasu; Sumiyoshi, Akira; Nonaka, Hiroi et al. (2015) Specific regions display altered grey matter volume in ?-opioid receptor knockout mice: MRI voxel-based morphometry. Br J Pharmacol 172:654-67
Musci, Rashelle J; Uhl, George; Maher, Brion et al. (2015) Testing gene × environment moderation of tobacco and marijuana use trajectories in adolescence and young adulthood. J Consult Clin Psychol 83:866-74
Zhong, Xiaoming; Drgonova, Jana; Li, Chuan-Yun et al. (2015) Human cell adhesion molecules: annotated functional subtypes and overrepresentation of addiction-associated genes. Ann N Y Acad Sci 1349:83-95
Drgonova, Jana; Walther, Donna; Singhal, Sulabh et al. (2015) Altered CSMD1 Expression Alters Cocaine-Conditioned Place Preference: Mutual Support for a Complex Locus from Human and Mouse Models. PLoS One 10:e0120908
Kitanaka, Junichi; Kitanaka, Nobue; Hall, F Scott et al. (2015) Memory impairment and reduced exploratory behavior in mice after administration of systemic morphine. J Exp Neurosci 9:27-35
Musci, Rashelle J; Bradshaw, Catherine P; Maher, Brion et al. (2014) Erratum to: Reducing Aggression and Impulsivity Through School-Based Prevention Programs: A Gene by Intervention Interaction. Prev Sci :

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