Research with rats germane to medication for alcoholism: consequences of noncompliance

Results of prior work indicate that (a) rats take stable, toxic levels of ethanol when they receive a daily regimen of limited opportunities to take both water and sweetened ethanol solution and (b) the combination of isradipine plus naltrexone persistently reduces those intakes. What are the effects of periodically missing doses of isradipine, naltrexone, or both? That is, what are the effects of differing levels of compliance? To get relevant information, rats were placed on a daily regimen, leading them to take, by choice, large amounts of ethanol (>2.0 g of ethanol per kilogram of body weight during 2 h a day). After being on this regimen for more than 60 days and after 28 days of no opportunity to take ethanol, 55 rats were divided into five groups. The opportunity to drink was then reinstated. One group received placebos, and another group received the combination of isradipine plus naltrexone daily. The other three groups received doses periodically, thereby conforming to good, moderate, and poor compliance. After abstinence, the intakes for rats receiving placebos rapidly returned to high levels. Intakes for rats receiving daily isradipine plus naltrexone did not return to high levels. The intakes for the other three groups were intermediate to intakes of the reference groups, corresponding to frequency of medication. When medication was not given, intakes approached placebo control levels, but the combination of isradipine plus naltrexone was effective when given subsequently. Daily dosing clearly is effective in reducing intakes, and suspension of dosing leads to higher intakes. A missed day of dosing, however, has limited consequences, provided that administration of medication is resumed.