Voluntary induction and maintenance of alcohol dependence in rats using alcohol vapor self-administration.
BACKGROUND
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.


OBJECTIVE
To address this issue, we developed a novel apparatus that vaporizes alcohol for 2-10 min after an active nosepoke response.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Neuroscience, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA, 92037, USA.
Giordano
G
de Guglielmo
Department of Neuroscience, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA, 92037, USA.
Marsida
M
Kallupi
Department of Neuroscience, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA, 92037, USA.
Maury D
MD
Cole
Department of Neuroscience, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA, 92037, USA. ogeorge@scripps.edu.
Olivier
O
George
D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000523:psychology*; D003216:Conditioning, Operant / Q000502:physiology*; D004195:Disease Models, Animal; D000431:Ethanol / Q000097:blood*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013375:Substance Withdrawal Syndrome
D000431:Ethanol
Addiction; Alcohol; Anxiety; Dependence; Vapor; Withdrawal