11. Opiate-ethanol Interaction Studies

Andrew K.S. Ho, Raymond C.A. Chen and J. Michael Morrison* Peoria School of Medicine, University of Illinois, Peoria, Illinois, and National Institute on Drug Abuse, Rockville, Maryland. * This work was supported by a contract from NIDA ADM-45-74220. The authors wish to thank Drs. Monique Braude, Lou Harris, Mary Jean Kreek, Elliot Vessel and Charles Schuster for valuable suggestions, and encouragement . INTRODUCTION Widespread use of alcohol among addicts has been reported by many investigators. Jackson and Richman (1) noted that many narcotic addicts would use alcohol when drugs such as heroin, morphine or cocaine were not available. In New York City during the period from 1950 to 1961 (2) one-tenth of the deaths among narcotic addicts were attributed to the combined use of narcotics and alcohol. Baden (3) reported that more than one-fifth of the heroin addicts who died in New York City had evidence of alcohol abuse. Addicts participating in methadone maintenance programs reported concomitant heavy use of alcohol (4,5). Heroin addicts maintained on prolonged methadone treatment and secondarily addicted to alcohol, develop a ten-fold increase in mortality over those who were on methadone maintenance alone (6). Similar increases in lethality were reported in animals treated with both narcotics and alcohol. In mice pretreated with alcohol, morphine administration markedly increased lethality (7). The depressant effects of alcohol are markedly potentiated by morphine (8). Sinclair et al. (9) observed that the selection of alcohol in Sprague-Dawley rats was suppressed after a single injection of morphine (60 mg/kg). In our laboratory, we have used both rats and mice to study the interaction between narcotics and alcohol. To further clarify opiate-ethanol interactions, and in particular, to test whether previous exposure to either opiate agonists or antagonist (acute, chronic and withdrawal following Chronic administration) affect alcohol selection, the following experiments were performed. Preliminary results of these studies have been reported elsewhere (10,11). MATERIALS AND METHODS ANIMALS The following strains of rats and mice were used: (a) adult male Sprague-Dawley rats weighing 180-200 g; (b) adult male Long-Evans Hooded rats weighing 180-220 g; (c) adult male C57BL/J6 mice weighing 20-25 g; and (d) neonatal Sprague-Dawley rats of both sexes. DRUGS AND CHEMICALS The drugs and chemicals used were: morphine sulfate (Merck Chemical Co.), methadone