Voluntary induction and maintenance of alcohol dependence in rats using alcohol vapor self-administration
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A major issue in the addiction field is the limited number of animal models of the voluntary induction and maintenance of alcohol dependence in outbred rats.
To address this issue, we developed a novel apparatus that vaporizes alcohol for 2–10 min after an active nosepoke response.
Male Wistar rats were allowed to self-administer alcohol vapor for 8 h/day every other day for 24 sessions (escalated) or eight sessions (non-escalated). Escalated and non-escalated rats were then tested for progressive ratio responding. Anxiety-like behavior, somatic signs of withdrawal, and hyperalgesia were assessed during acute withdrawal.
The results showed that rats exhibited excellent discrimination between the active and inactive operanda (>85%), and the escalated rats quickly increased their blood alcohol levels from ~50 to >200 mg% in ~6 weeks. Compared with non-escalated rats, escalated rats exhibited severe addiction-like behavior, including somatic signs of withdrawal, anxiety-like behavior, hyperalgesia, and higher responding on a progressive ratio schedule of reinforcement.
These results demonstrate that outbred rats will voluntarily self-administer alcohol vapor to the point of dependence without the use of forced alcohol administration, sweeteners, food/water restriction, operant pretraining, or behavioral/genetic selection. This novel animal model may be particularly useful for medication development to help unveil the neuronal circuitry that underlies the voluntary induction of alcohol addiction and identify novel molecular targets that are specifically recruited after the voluntary induction and maintenance of alcohol dependence.
KeywordsAddiction Alcohol Dependence Vapor Withdrawal Anxiety
The authors thank Michael Arends for proofreading the manuscript.
GdG and OG were responsible for the study concept and design. GdG, MC, and OG developed the new apparatus. GdG, MK, and MC contributed to the acquisition of animal data. GdG and OG drafted the manuscript. All authors critically reviewed the content and approved the final version for publication.
Compliance with ethical standards
All of the procedures were conducted in strict adherence to the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee of The Scripps Research Institute.
Funding and disclosure
This study was supported by the National Institutes of Health grants AA006420, AA020608, and AA022977 (OG). MDC is the owner of La Jolla Alcohol Research inc. (LJARi). OG is a consultant for the National Institute of Health, LJARi, and Simply-Lab LLC. OG, MDC, and GdG have co-invented and co-developed the apparatus described in this manuscript. The other authors declare no conflict of interest.
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