Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats.
BACKGROUND
Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans.


OBJECTIVE
The present experiments utilized a "reinforcer blocking" approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats.


METHODS
In "nondependent" experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For "dependent" experiments, rats were made dependent in vapor/inhalation chambers.


RESULTS
Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate's effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats.


CONCLUSIONS
The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The "nondependent" paradigm may model early stages of "problem drinking" in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.
Czachowski
Cristine L
CL
Center for Alcohol and Addiction Studies, Brown University, Providence, RI 02912, USA. cczachow@iupui.edu
Delory
Michael J
MJ
D000077443:Acamprosate; D000427:Alcohol Deterrents / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000523:psychology; D000437:Alcoholism / Q000188:drug therapy* / Q000523:psychology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D003627:Data Interpretation, Statistical; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D013395:Sucrose / Q000494:pharmacology*; D013649:Taste / Q000187:drug effects*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000427:Alcohol Deterrents; D013654:Taurine; D013395:Sucrose; D009271:Naltrexone; D000077443:Acamprosate