Behavior Genetics of Drug Sensitization
Abstract
Recent history has seen a surge of interest in the phenomenon of drug sensitization (reverse tolerance), in part because sensitization has been suggested as an important factor in the development of drug abuse. Genetic variation plays a key role in sensitivity to many drug effects, as well as predilection toward alcohol and drug abuse. The goal of this review was to critically evaluate the literature investigating the behavioral genetics of drug sensitization. A moderate amount of animal work utilizing inbred strains, selected lines, and recombinant inbred strains has been done that unsurprisingly supports partial genetic control of sensitization. Genes determining quantitative variation in degree of sensitization to cocaine and ethanol have been provisionally mapped to specific chromosomal regions in the mouse. However, research toward establishing a link between sensitization and risk for drug abuse and toward identifying the genetic mediators of sensitization needs to be expanded. Information derived from congenic strains, transgenic mice, knockout and inducible knockout mice could lead to better medical intervention for drug addiction.
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In animals, there are genetic differences in the propensity of individual brains to undergo sensitization, and in the functioning of the mesolimbic dopamine system.
“To date, it has been shown in animals that there are genetic differences in the propensity of individual brains to undergo sensitization, and in the functioning of the mesolimbic dopamine system (Dietz, Tapocik, Gaval-Cruz, & Kabbaj, 2005; Phillips, 1997).”
From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as Phillips, 1997
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“There are few reports on genetic/strain differences in determining vulnerability to different drugs [9,23,33,34,38,43].”
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“This “locomotor sensitization” provides an experimental model to study the molecular mechanisms underlying the neural and behavioral adaptations occurring with repeated psychostimulant use, with potential relevance to the development of addiction (Everitt and Wolf 2002; Phillips 1997; Robinson and Berridge 2003).”
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“To date, it has been shown in animals that there are genetic differences in the propensity of individual brains to undergo sensitization, and in the functioning of the mesolimbic dopamine system (Dietz, Tapocik, Gaval-Cruz, & Kabbaj, 2005; Phillips, 1997).”
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“A number of studies have taken advantage of the availability of different inbred mouse strains to investigate the genetic basis of susceptibility to the sensitizing effects of cocaine (Tolliver et al., 1994; Elmer et al., 1996; Phillips, 1997; Phillips et al., 1998).”
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“This report describes differences in NAC glutamate receptorassociated protein expression between two inbred mouse strains, C57BL/6J (B6) and DBA2/J (D2) mice, which are highly utilized for studying the neurogenetics of alcoholism (Crabbe 2002; Phillips 1997).”
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- Authors
- Phillips, T. J.
- Affiliations
- Oregon Health & Science University (US)
- Corresponding author
- Phillips, Tamara J.
- ORCID
- Phillips, Tamara J.
- Venue
- Critical Reviews™ in Neurobiology
- Publisher
- Begell House
- Published
- 1997
- Volume
- 11
- Issue
- 1
- Pages
- 21-33
- ISSN
- 0892-0915 (ISSN-L)
- OpenAlex
- W2081544021
- Cited by
- 54
- References
- 0
- Citations by year
- 2024: 1 · 2021: 2 · 2019: 1 · 2018: 2 · 2014: 3 · 2013: 2
- FWCI
- 1.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Critical Reviews in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01aa008621-05)
- National Institute on Alcohol Abuse and Alcoholism (AA-08621, P60AA010760)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- drug sensitization, reverse tolerance, behavioral genetics, cocaine sensitization, ethanol sensitization, inbred mouse strains, recombinant inbred lines, selected lines, gene mapping, congenic strains, knockout mice, transgenic mice, substance abuse risk, addiction
- MeSH terms
- Animals, Behavior, Behavior, Animal, Dose-Response Relationship, Drug, Humans, Individuality, Mice, Inbred Strains, Rats, Inbred Strains, Genetic Variation, Substance-Related Disorders, Mice, Rats
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