Download Molecular Biology of Drug Addiction by Rafael Maldonado PDF

By Rafael Maldonado

A complete multidisciplinary assessment of the main correct molecular, genetic, and behavioral methods used to enquire the neurobiological foundation of drug dependancy. The authors discover the newest findings on opioid, psychostimulant, cannabinoid, alcohol, and nicotine habit, supply clean insights into the genetic foundation of drug dependancy and the hot healing views those have opened. They describe the expertise to be had to generate conditional knockout mice and express how those mice can show the molecular foundation of opioid, psychostimulant, and cannabinoid dependancy. in addition they evaluate the various behavioral versions to be had to judge the profitable results of gear and study the genes excited about alcohol dependence.

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A) Once mice homozygous for the CREB loxP allele are crossed with mice expressing Cre recombinase specifically in brain, the result is CREB loss restricted to the nervous system. Use of various Cre transgenic lines would result in distinct anatomical and temporal patterns of CREB gene ablation. (B) Cre-recombinase expression under the control of the nestin promoter and enhancer results in almost complete CREB loss in brain. CREBloxP brains show normal widespread nuclear protein expression revealed by using anti-CREB antibodies, while CREBNesCre mutant mice exhibit almost complete loss of CREB protein.

Lichtman, A. , Sheikh, S. , Loh, H. , and Martin, B. R. (2001) Opioid and cannabinoid modulation of precipitated withdrawal in delta(9)-tetrahydrocannabinol and morphine-dependent mice. J. Pharmacol. Exp. Ther. 298, 1007–1014. 38. , Samad, T. , Roques, B. , and Borrelli, E. (1997) Absence of opiate rewarding effects in mice lacking dopamine D2 receptors. Nature 388, 586–589. 39. Dockstader, C. , Grandy, D. , Low, M. , and van der Kooy, D. (2001) The D2 receptor is critical in mediating opiate motivation only in opiate-dependent and withdrawn mice.

2. Role for CREB in the Locus Coeruleus Many long-lasting, activity-dependent changes in neuronal function are mediated by changes in gene transcription. This occurs via activity-dependent regulation of transcription factors, proteins that recognize and bind to specific DNA sites within the genes they control. These transcription factors then influence gene expression and contribute to the long-lasting phenotypic changes in neurons. One of the best-characterized transcription factors in the nervous system is CREB (cAMP response element-binding protein).

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