Document Detail

The effect of doxycycline on alcohol consumption and sensitivity: consideration for inducible transgenic mouse models.
MedLine Citation:
PMID:  23019604     Owner:  NLM     Status:  MEDLINE    
Neuroinflammation is known to elicit numerous changes in brain physiology and is associated with various pathologies, including neurodegenerative diseases, and behaviors, such as sleep and acute illness. In addition, there is accumulating evidence that the behavioral response to alcohol is affected by perturbations to the neuroimmune system. Recent studies have shown that administration of proinflammatory mediators increases alcohol consumption, while anti-inflammatory drugs, such as minocycline, decrease consumption. Doxycycline is an anti-inflammatory mediator and a tetracycline derivative, and is commonly used in the tetracycline regulatory system, a transgenic approach widely accredited for its inducible and reversible nature. Given the established link between anti-inflammatory agents and response to and consumption of alcohol, and because the tetracycline regulatory system is becoming increasingly employed for genetic manipulations and behavioral phenotyping, we investigated the effect of doxycycline administration on alcohol sensitivity and consumption. Two independent transgenic lines containing a tetracycline transactivator transgene or the tetracycline operator promoter insertion, along with wild-type littermate mice (C57Bl/6J), were used to measure changes in alcohol consumption, alcohol-induced motor impairment and sedation, and blood alcohol concentration with doxycycline administration (40 mg/kg in chow). Using repeated sessions of the drinking-in-the-dark paradigm, we found that doxycycline consistently reduced consumption of 20% alcohol during two- and four-hour access. Doxycycline also increased sensitivity to the motor-impairing effects of alcohol (2 g/kg), and the duration of loss of righting reflex after ethanol injection (3.5 g/kg), without causing a significant alteration in blood alcohol levels. Despite the many advantages of using a tetracycline-regulated transgenic approach, it is important to consider the effects of doxycycline administration in behaviors that may be influenced by neuroinflammation, including alcohol behaviors.
Sally R McIver; Megan M Muccigrosso; Philip G Haydon
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-09-27
Journal Detail:
Title:  Experimental biology and medicine (Maywood, N.J.)     Volume:  237     ISSN:  1535-3699     ISO Abbreviation:  Exp. Biol. Med. (Maywood)     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-11-01     Completed Date:  2013-02-05     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  100973463     Medline TA:  Exp Biol Med (Maywood)     Country:  England    
Other Details:
Languages:  eng     Pagination:  1129-33     Citation Subset:  IM    
Department of Neuroscience, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA.
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MeSH Terms
Alcohol Drinking / metabolism*,  psychology
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage,  pharmacology*
Behavior, Animal / drug effects
Doxycycline / administration & dosage,  pharmacology*
Ethanol / pharmacology*
Mice, Inbred C57BL
Mice, Transgenic
Promoter Regions, Genetic
Tetracycline / pharmacology
Trans-Activators / genetics
Grant Support
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Trans-Activators; 564-25-0/Doxycycline; 60-54-8/Tetracycline; 64-17-5/Ethanol

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