Pharmacogenetics; alcohol and dependence; alcohol binge drinking; drug discovery
Summary of Current Research
I have developed mouse pharmacogenetic models for dependence on ethanol by selectively breeding lines of mice resistant, or susceptible, to the severity of withdrawal from ethanol dependence. We have developed a more comprehensive set of behavioral assays characterizing withdrawal severity. With my collaborators we are analyzing the genomic changes underlying the large differences between the Withdrawal Seizure-Prone and -Resistant lines.
Other approaches include studies of multiple inbred strains of mice examining the basis for genetic correlations between susceptibilities to different effects of ethanol and different drugs of abuse. These studies have explored the specificity of genetic influences across different environments, including multiple laboratories. They are also intended to elucidate gene-environment interactions. Strain patterns of sensitivity sometimes indicate the important influence of single genes on drug responses.
We have also developed new lines of mice selectively bred for binge Drinking in the Dark as a part of the Integrative Neuroscience Initiative on Alcoholism (INIA-Neuroimmune) consortium. These mice drink to the point of intoxication, reaching average blood levels higher than the legal driving limit. We are exploring the pharmacological characteristics of the neural circuitry underlying this drinking as well as the behavioral characteristics of these mice. We are using these mice as a model for testing novel drugs that could ameliorate drinking and we are exploring their use in informatics-driven genomics studies.
Research Fellow, Organon International BV, Oss, the Netherlands
Lecturer, University of California
Areas of interest
- Mouse behavior
- Alcohol and drug abuse
- Genetic animal models
- Binge drinking
- Drug dependence
- Drug tolerance
- M.A., University of Colorado 1972
- Ph.D., University of Colorado 1973
- B.A., Stanford University 1968
- "High Drinking in the Dark (HDID) mice are sensitive to the effects of some clinically relevant drugs to reduce binge-like drinking." Pharmacology Biochemistry and Behavior In: , Vol. 160, 01.09.2017, p. 55-62.
- "Ethanol withdrawal-induced dysregulation of neurosteroid levels in plasma, cortex, and hippocampus in genetic animal models of high and low withdrawal." Psychopharmacology In: , 29.06.2017, p. 1-19.
- "Prefrontal cortex expression of chromatin modifier genes in male WSP and WSR mice changes across ethanol dependence, withdrawal, and abstinence." Alcohol In: , Vol. 60, 01.05.2017, p. 83-94.
- "Alignment of the transcriptome with individual variation in animals selectively bred for High Drinking-In-the-Dark (HDID)." Alcohol In: , Vol. 60, 01.05.2017.
- "Reproducibility of Experiments with Laboratory Animals : What Should We Do Now?" Alcoholism: Clinical and Experimental Research In: , Vol. 40, No. 11, 01.11.2016, p. 2305-2308.
- "Effects of acute alcohol withdrawal on nest building in mice selectively bred for alcohol withdrawal severity." Physiology and Behavior In: , Vol. 165, 15.10.2016, p. 257-266.
- "Progress with nonhuman animal models of addiction." Journal of Studies on Alcohol and Drugs In: , Vol. 77, No. 5, 01.09.2016, p. 696-699.
- "Fear conditioning in mouse lines genetically selected for binge-like ethanol drinking." Alcohol In: , Vol. 52, 01.05.2016, p. 25-32.
- "Nest building is a novel method for indexing severity of alcohol withdrawal in mice." Behavioural Brain Research In: , Vol. 302, 01.04.2016, p. 182-190.
- "Neuropeptide Y response to alcohol is altered in nucleus accumbens of mice selectively bred for drinking to intoxication." Behavioural Brain Research In: , Vol. 302, 01.04.2016, p. 160-170.
- "Protein kinase C epsilon activity in the nucleus accumbens and central nucleus of the amygdala mediates binge alcohol consumption." Biological Psychiatry In: , Vol. 79, No. 6, 15.03.2016, p. 443-451.
- "Corrigendum to Distinct ethanol drinking microstructures in two replicate lines of mice selected for drinking to intoxication [Genes, Brain and Behavior 14, 5, (2015), 398-410] DOI : 10.1111/gbb.12225." Genes, Brain and Behavior In: , Vol. 15, No. 3, 01.03.2016, p. 356.
- "Gene Targeting Studies of Hyperexcitability and Affective States of Alcohol Withdrawal in Rodents." International Review of Neurobiology In: , 2016.
- "Commonalities and Distinctions Among Mechanisms of Addiction to Alcohol and Other Drugs." Alcoholism: Clinical and Experimental Research In: , Vol. 39, No. 10, 01.10.2015, p. 1863-1877.
- "Distinct ethanol drinking microstructures in two replicate lines of mice selected for drinking to intoxication." Genes, Brain and Behavior In: , Vol. 14, No. 5, 01.06.2015, p. 398-410.
- "Genotypic and sex differences in anxiety-like behavior and alcohol-induced anxiolysis in High Drinking in the Dark selected mice." Alcohol In: , Vol. 49, No. 1, 01.02.2015, p. 29-36.
- "Rewarding and aversive effects of ethanol in High Drinking in the Dark selectively bred mice." Addiction Biology In: , Vol. 20, No. 1, 01.01.2015, p. 80-90.
- "Dual-Trait Selection for Ethanol Consumption and Withdrawal : Genetic and Transcriptional Network Effects." Alcoholism: Clinical and Experimental Research In: , Vol. 38, No. 12, 01.12.2014, p. 2915-2924.
- "Addiction." Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease: Fifth Edition. Elsevier Inc., 2014. p. 1321-1329.
- "Experimenter effects on behavioral test scores of eight inbred mouse strains under the influence of ethanol." Behavioural Brain Research In: , Vol. 272, 01.10.2014, p. 46-54.
- "Quantification of ten neuroactive steroids in plasma in Withdrawal Seizure-Prone and -Resistant mice during chronic ethanol withdrawal." Psychopharmacology In: , Vol. 231, No. 17, 01.09.2014, p. 3401-3414.
- "Neurobiology of Alcohol Dependence." Elsevier Inc., 2014. 560 p.
- "Progress in a replicated selection for elevated blood ethanol concentrations in HDID mice." Genes, Brain and Behavior In: , Vol. 13, No. 2, 02.2014, p. 236-246.
- "The Genetic Complexity of Alcohol Drinking in Rodents." Neurobiology of Alcohol Dependence. Elsevier Inc., 2014. p. 359-375.
- "Alcohol-use disorders." Behavioral Genetics of the Mouse Volume II: Genetic Mouse Models of Neurobehavioral Disorders. Cambridge University Press, 2014. p. 293-302.
- "The genetics of gene expression in complex mouse crosses as a tool to study the molecular underpinnings of behavior traits." Mammalian Genome In: , Vol. 25, No. 1-2, 2014, p. 12-22.
- "Identification of a QTL in Mus musculus for alcohol preference, withdrawal, and Ap3m2 expression using integrative functional genomics and precision genetics." Genetics In: , Vol. 197, No. 4, 2014, p. 1377-1393.
- "Rodent models of genetic contributions to motivation to abuse alcohol." Nebraska Symposium on Motivation In: , Vol. 61, 2014, p. 5-29.
- ""Drinking in the dark" (DID) : A simple mouse model of binge-like alcohol intake." Current Protocols in Neuroscience In: , No. SUPP.68, 9.49, 2014.
- "Genetic relationship between predisposition for binge alcohol consumption and blunted sensitivity to adverse effects of alcohol in mice." Alcoholism: Clinical and Experimental Research In: , Vol. 38, No. 5, 2014, p. 1284-1292.