Early experience and the consumption of alcohol by adult C57BL/6J mice.

Two types of early experience were examined for their effect on voluntary alcohol consumption by adult C57BL/6J mice: the experiences associated with belonging to a particular litter, and the experience of early postweaning choice between water and a 10% alcohol solution. Males from identified litters were individually caged from arrival at three weeks of age and given a choice between 10% alcohol and water when eight weeks old. Another group without notation of litter was given alcohol-water choice upon arrival at three weeks of age. Alcohol intake was examined by three measures: daily licks of 10% alcohol, alcohol selection (percent alcohol drinking), and volume of alcohol drunk daily. Belonging to a particular litter did affect body weight and growth, but had no effect on adult consumption of alcohol. Postweaning exposure to alcohol choice, however, produced a small but significant and prolonged increase in alcohol consumption by adults. Furthermore, a developmental trend was found in mice offered alcohol choice at an early age: alcohol preference developed as postweaning growth slowed.

Implications of methadone maintenance for theories of narcotic addiction.

Clinical success in rehabilitation of heroin addicts with maintenance treatment requires stability of the blood level in a pharmacologically effective range (optimally, 150 to 600 ng/mL)-a phenomenon that emphasizes the central importance of narcotic receptor occupation. It is postulated that the high rate of relapse of addicts after detoxification from heroin use is due to persistent derangement of the endogenous ligand-narcotic receptor system and that methadone in an adequate daily dose compensates for this defect. Some patients with long histories of heroin use and subsequent rehabilitation on a maintenance program do well when the treatment is terminated. The majority, unfortunately, experience a return of symptoms after maintenance is stopped. The treatment, therefore, is corrective but not curative for severely addicted persons. A major challenge for future research is to identify the specific defect in receptor function and to repair it. Meanwhile, methadone maintenance provides a safe and effective way to normalize the function of otherwise intractable narcotic addicts.

Methadone maintenance patients in general medical practice. A preliminary report.

Medical maintenance is the treatment by primary care physicians of rehabilitated methadone maintenance patients who are stable, employed, not abusing drugs, and not in need of supportive services. In this research project, physicians with experience in drug abuse treatment provided both the pharmacologic treatment of addiction as well as therapy for other medical problems, as needed. Decisions regarding treatment were based on the individual needs of the patient and on currently accepted medical practice rather than on explicit regulations. We studied the first 40 former heroin addicts who were transferred to this program from more conventional methadone clinics. At a follow-up visit at 12 to 55 months, 33 (82.5%) of 40 patients had remained in treatment; five (12.5%) had been discharged because of cocaine abuse and two (5%) had been voluntarily discharged. Personal benefits of medical maintenance include the dignity of a standard professional atmosphere and a more flexible reporting schedule. This program has the potential for improving treatment of selected methadone maintenance patients.

Manipulation of alcohol preference in C57BL/6J mice by episodes of food poisoning.

Individual differences in the amount of alcohol consumed in a choice situation are found in highly inbred C57BL/6J mice. The extent to which environmental stress can modify alcohol preference was studied by coupling acute episodes of poisoning with restricted fluid availability, and recovery with free choice of drinking fluids. Addition of actinomycin D, a mycotoxin, to ordinary chow during 2-day periods produced acute episodes of nonlethal food poisoning from which the mice recovered rapidly. Consumption of a 10% alcohol solution and of water was recorded for several weeks before poisoning and for several weeks after the last episode. By varying drinking fluids available to the mice during the episodes of poisoning, long-lasting changes in alcohol preference were produced. When 10% alcohol was the sole drinking fluid available during poisoning, preference for the alcohol solution was abolished. When water was the sole fluid during poisoning, alcohol preference was increased above the already high levels established in the baseline and above a control group that was restricted to water during the treatment periods but was not poisoned. This increased alcohol preference was due to a nearly complete suppression of water intake in the posttreatment period; there was no significant increase in amount of alcohol consumed. The greatest individual differences in subsequent alcohol preference were found in the group of mice which continued to have free choice of alcohol and water during episodes of poisoning. The variety of responses to the same treatment show how environmental influences outside the experimenter's control may account for the variability found in voluntary alcohol consumption among genetically homogeneous mice.

Toward an analogue of alcoholism in mice: analysis of nongenetic variance in consumption of alcohol.

Drinking behavior of the isogenic mouse strain C57BL/6J was analyzed into nongenetic components: stochastic fluctuations, responses to fluctuations in the current environment, and persistent differences between individual animals. The latter accounted for the major part of the variance. The variance was neither increased by differences in diet during the postweaning rapid growth period (prior to assay for drinking choice) nor diminished by uniformity of treatment during this period, suggesting that significant differentiation had occurred prior to weaning. The large variance between animals could be explained by assuming that the genetic role in consumption of alcohol by C57BL mice is permissive--a relative insensitivity to the aversive orosensory and pharmacological effects of 10% alcohol--rather than a specific drug-seeking predisposition.

Why does a sucrose choice reduce the consumption of alcohol in C57BL/6J mice?

To determine why animals reject alcohol when offered palatable solutions of sucrose, male C57BL/6J mice were challenged first with 5% sucrose then with 10% sucrose, while given continuous free-access to alcohol and water. The 5% sucrose dramatically reduced the intake of alcohol and increased the intake of total fluid by an average of 7.3 ml/day. The suppression of alcohol intake could not be attributed to a volumetric ceiling since access to 10% sucrose produced a further large increase in total intake (8.8 ml/day). The results support the interpretation that animals consume alcohol for characteristics it shares with sucrose.

Toward an analogue of alcoholism in mice: criteria for recognition of pharmacologically motivated drinking.

Two criteria of alcoholic drinking behavior--inelasticity of demand and dissociation of intake from normal eating and drinking--are illustrated by study of alcohol-preferring C57BL/6J mice. Although these mice drink enough to become intoxicated for brief periods each night, they do not meet the more rigorous criteria for pharmacologically motivated drinking. Their intake of alcohol was dramatically decreased when they were offered diets augmented with sugar or Crisco, and the temporal pattern of drinking was correlated with the intake of food. Thus, their motivation for drinking alcohol is related to nutrition and is not drug-seeking comparable to that of human alcoholics. Since the tests are simple and decisive, it might be useful to apply them to all putative models of alcoholism.