Progress With Nonhuman Animal Models of Addiction.

Nonhuman animals have been major contributors to the science of the genetics of addiction. Given the explosion of interest in genetics, it is fair to ask, are we making reasonable progress toward our goals with animal models? I will argue that our goals are changing and that overall progress has been steady and seems likely to continue apace. Genetics tools have developed almost incredibly rapidly, enabling both more reductionist and more synthetic or integrative approaches. I believe that these approaches to making progress have been unbalanced in biomedical science, favoring reductionism, particularly in animal genetics. I argue that substantial, novel progress is also likely to come in the other direction, toward synthesis and abstraction. Another area in which future progress with genetic animal models seems poised to contribute more is the reconciliation of human and animal phenotypes, or consilience. The inherent power of the genetic animal models could be more profitably exploited. In the end, animal research has continued to provide novel insights about how genes influence individual differences in addiction risk and consequences. The rules of the genetics game are changing so fast that it is hard to remember how comparatively little we knew even a generation ago. Rather than worry about whether we have been wasting time and resources asking the questions we have been, we should look to the future and see if we can come up with some new ones. The valuable findings from the past will endure, and the sidetracks will be forgotten.

[1]  K. Deisseroth,et al.  Illuminating next-generation brain therapies , 2016, Nature Neuroscience.

[2]  Sheena A. Josselyn,et al.  Advanced In vivo Use of CRISPR/Cas9 and Anti-sense DNA Inhibition for Gene Manipulation in the Brain , 2016, Front. Genet..

[3]  Neville E. Sanjana,et al.  High-throughput functional genomics using CRISPR–Cas9 , 2015, Nature Reviews Genetics.

[4]  C. Ferreira,et al.  Splice variants in the proteome: a promising and challenging field to targeted drug discovery. , 2015, Drug discovery today.

[5]  S. Skaper,et al.  MicroRNAs: emerging role in the endogenous μ opioid system. , 2015, CNS & neurological disorders drug targets.

[6]  A. Isles Neural and behavioral epigenetics; what it is, and what is hype , 2015, Genes, brain, and behavior.

[7]  Jeremy J. Jay,et al.  Identification of a QTL in Mus musculus for Alcohol Preference, Withdrawal, and Ap3m2 Expression Using Integrative Functional Genomics and Precision Genetics , 2014, Genetics.

[8]  Y. Shaham,et al.  New technologies for examining the role of neuronal ensembles in drug addiction and fear , 2013, Nature Reviews Neuroscience.

[9]  D. Lovinger,et al.  Loss of metabotropic glutamate receptor 2 escalates alcohol consumption , 2013, Proceedings of the National Academy of Sciences.

[10]  J. Crabbe,et al.  Selection for drinking in the dark alters brain gene coexpression networks. , 2013, Alcoholism, clinical and experimental research.

[11]  D. Bottomly,et al.  Genes, behavior and next‐generation RNA sequencing , 2013, Genes, brain, and behavior.

[12]  Michael A. Langston,et al.  GeneWeaver: a web-based system for integrative functional genomics , 2011, Nucleic Acids Res..

[13]  D. Goldman,et al.  The genetics of alcoholism and alcohol abuse , 2001, Current psychiatry reports.

[14]  R. Nelson,et al.  Behavior in Mice with Targeted Disruption of Single Genes , 1998, Neuroscience & Biobehavioral Reviews.

[15]  J. A. Chester,et al.  Mice Lacking Dopamine D4 Receptors Are Supersensitive to Ethanol, Cocaine, and Methamphetamine , 1997, Cell.

[16]  J. Crabbe,et al.  Genetic animal models of alcohol and drug abuse. , 1994, Science.

[17]  J. Mardones,et al.  Thirty-two years of selection of rats by ethanol preference: UChA and UChB strains. , 1983, Neurobehavioral toxicology and teratology.

[18]  G. Mcclearn,et al.  Differences in Alcohol Preference among Inbred Strains of Mice , 1959 .

[19]  O. Iancu,et al.  Coexpression and cosplicing network approaches for the study of mammalian brain transcriptomes. , 2014, International review of neurobiology.

[20]  G. Koob,et al.  Neurobiology of Alcohol Dependence , 2008, Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism.

[21]  Ting-kai Li,et al.  NEW STRAINS OF RATS WITH ALCOHOL PREFERENCE AND NONPREFERENCE , 1977 .