Journal Article•
Experimentally induced intoxication in alcoholics: a comparison between programed and spontaneous drinking
01 May 1970-Journal of Pharmacology and Experimental Therapeutics (American Society for Pharmacology and Experimental Therapeutics)-Vol. 173, Iss: 1, pp 101-116
TL;DR: It is concluded that the two drinking patterns produce significant differences in biologic and behavioral correlates of intoxication and withdrawal, and results obtained with programed alcohol administration may be of more limited generality in clarifying the complex determinants of the clinical expression of alcohol addiction.
Abstract: The effects of the pattern (spontaneous or programed) of alcohol intake on the behavioral and biologic responses of eight chronic alcoholic males were observed. Subjects drank for 20 days in each condition and underwent a period of alcohol abstinence after each drinking episode. All subjects drank more, achieved higher blood alcohol levels and tolerated alcohol better during the spontaneous drinking paradigm. The contribution of metabolic, endocrine and caloric factors to observed differences in blood alcohol levels are discussed. All subjects showed more severe withdrawal signs and symptoms upon cessation of spontaneous than of programed drinking. This finding suggests that the pattern of drinking is more important than duration of drinking in determining the expresion of withdrawal signs and symptoms. Sleep patterns during intoxication tended to be fragmented in comparison to base-line sleep patterns. Withdrawal signs and symptoms were correlated with sleep fragmentation and/or somnolence rather than with insomnia. The possible relationship of alcohol-induced sleep fragmentation and affective changes observed during intoxication are discussed. It is concluded that the two drinking patterns produce significant differences in biologic and behavioral correlates of intoxication and withdrawal. Results obtained with programed alcohol administration may be of more limited generality in clarifying the complex determinants of the clinical expression of alcohol addiction.
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TL;DR: A reformulation of the negative reinforcement model of drug addiction is offered and it is proposed that the escape and avoidance of negative affect is the prepotent motive for addictive drug use.
Abstract: This article offers a reformulation of the negative reinforcement model of drug addiction and proposes that the escape and avoidance of negative affect is the prepotent motive for addictive drug use. The authors posit that negative affect is the motivational core of the withdrawal syndrome and argue that, through repeated cycles of drug use and withdrawal, addicted organisms learn to detect interoceptive cues of negative affect preconsciously. Thus, the motivational basis of much drug use is opaque and tends not to reflect cognitive control. When either stressors or abstinence causes negative affect to grow and enter consciousness, increasing negative affect biases information processing in ways that promote renewed drug administration. After explicating their model, the authors address previous critiques of negative reinforcement models in light of their reformulation and review predictions generated by their model.
1,791 citations
Cites background from "Experimentally induced intoxication..."
...Thus, withdrawal symptoms may occur even when drug levels in the body are quite high—just so long as they have declined from a higher level (e.g., Isbell, Fraser, Wikler, Belleville, & Eisenman, 1955; Mello & Mendelson, 1970)....
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...Rather, numerous studies (Mello & Mendelson, 1970; Parrott, 1999; Wikler, 1977, 1980; Zinser et al., 1992) have shown that addictive agents very quickly and efficiently reduce negative affect along with other elements of the withdrawal syndrome....
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TL;DR: It is suggested that early rearing experiences that predispose monkeys to increased fear-related behaviors produce excessive alcohol consumption under normal living conditions, and a major challenge such as social separation increases alcohol consumption to levels producing intoxication even in monkeys not particularly vulnerable to stress.
Abstract: Twenty-two 50-month-old rhesus monkeys were provided concurrent free access to an aspartame-sweetened 7% ethanol solution and an aspartame-sweetened vehicle before, during, and after social separation. Subjects had been reared for their first 6 months of life either without access to adults but with constant access to age mates (peer reared), a condition producing reduced exploration and increased fear-related behaviors, or as controls with their mothers; thereafter, all subjects received identical treatment. During home-cage periods, for 1 hr each day, 4 days a week, when the ethanol solution and vehicle were freely available, peer-reared subjects consumed significantly more alcohol than mother-reared subjects. When stress was increased via social separation, mother-reared animals increased their alcohol consumption to a level nearly as high as that of peer-reared monkeys. Average individual differences in alcohol consumption were markedly stable over time. In addition, there were strong positive correlations between alcohol consumption and distress behaviors. Biological indices of increased stress, such as plasma cortisol and corticotropin, were higher in peer-reared subjects. Within the peer- and mother-reared groups, these indices were positively correlated with alcohol consumption. The results suggest that early rearing experiences that predispose monkeys to increased fear-related behaviors produce excessive alcohol consumption under normal living conditions. Furthermore, a major challenge such as social separation increases alcohol consumption to levels producing intoxication even in monkeys not particularly vulnerable to stress.
368 citations
TL;DR: It appeared that a sufficient amount of alcohol, administered in the context of explicit drinking cues, could act much like hors d'oeuvres and thereby contribute to the "first drink" relapse phenomenon.
Abstract: This study attempts to explicate some of the major determinants of relapse in alcoholics by manipulating craving and alcohol acquisition behavior through appropriate interoceptive and exteroceptive stimulation. Subjective, behavioral, physiological, and neurophysiological measures were used with 24 chronic alcoholics, randomly assigned to one of two groups—label (L) and nonlabel (NL). In the L situation, exteroceptive cues—such as the clear sight and smell of alcohol—were conducive to appropriate "cognitive labeling." Alcoholic subjects in each group were administered either a placebo (P), high (Hi), or low dose (Lo) of alcohol. Consistent with the conditioning theory proposed, the results generally indicated that craving and alcohol acquisition behavior, as well as conversion from abstinence to alcohol acquisition, were a function of the combination of appropriate interoceptive and exteroceptive cues, with the Lo (L) group condition producing the greatest effects. It appeared that a sufficient amount of alcohol, administered in the context of explicit drinking cues, could act much like hors d'oeuvres and thereby contribute to the "first drink" relapse phenomenon.
365 citations
TL;DR: The data suggest that the reinforcing effects of EtOH and neurotransmitter pathways mediating reward are altered after the development of dependence, and they support the use of this paradigm for further investigations into the neuropharmacological mechanisms mediating reinforcement in dependent versus nondependent animals.
Abstract: Dependence is an important factor motivating continued alcohol use in human alcoholics. Development of a model of ethanol (EtOH) consumption in dependent animals would advance the understanding of reinforcement after chronic EtOH exposure and allow for the investigation of the neuropharmacological mechanisms mediating reinforcement in dependent versus nondependent animals. In the present study, rats were trained to lever press for 10% EtOH, surgically implanted with bilateral guide cannulae in the amygdala, and either made dependent on EtOH by exposure for 2 weeks to EtOH or exposed to air in identical vapor chambers. Upon removal, the rats were placed in operant boxes and allowed to respond on levers for 10% EtOH or water during a 12-hr period. Rats were removed briefly at approximately 6.5 hr for intra-amygdala injections of saline or the GABAA receptor agonist muscimol. After the test period, rats were returned to the vapor chambers for 4 days before retest. EtOH-dependent animals responded more for EtOH across the 12-hr test period than did air control nondependent rats; this difference became more pronounced with repeated test sessions. Intra-amygdala muscimol significantly decreased responding for EtOH in EtOH-dependent rats, but had no effect in nondependent controls. These data suggest that the reinforcing effects of EtOH and neurotransmitter pathways mediating reward are altered after the development of dependence, and they support the use of this paradigm for further investigations into the neuropharmacology of EtOH dependence.
326 citations
TL;DR: It is puzzling to find that Cirrhosis of the liver apparently develops only in a minor proportion of heavy drinkers and alcoholics, which seems to contradict the well-established association’ between alcoholism and cirrhosis.
Abstract: At first sight, it is puzzling to find that cirrhosis of the liver apparently develops only in a minor proportion of heavy drinkers and alcoholics, which seems to contradict the well-established association’ between alcoholism and cirrhosis. A statistic based on IOseries of autopsy records (TABLE 1) shows that the incidence of cirrhosis in alcoholics ranged from as low as 2.4% to a maximum figure of about 28%. This statistic is a partly corrected extension of original data from Jolliffe and Jellinek,54 who calculated an average incidence of only 8% as against an estimated 1.2% in the general nonalcoholic population. Varying diagnostic standards in a number of these older autopsy series may have contributed to an underrepresentation. The modified statistic presented here yields a higher average incidence, of 18%, which is largely due to the inclusion of Wilen’s selected sample. This sample is outstanding in that it takes account of the potential length of drinking history and of minimum levels of daily alcohol intake. In more recent series where liver biopsies were performed during life (TABLE 2), the incidence of cirrhosis among defined alcoholics, though definitely, higher, still reaches only 30%, which is close to Wilen’s percentage. According to crosssectional studies of this kind, it can be safely assumed that cirrhosis will develop only in roughly 4 to # of those who heavily indulge in alcohol abuse during a lengthy period of their lives. In my own series of 320 biopsy cases, wellestablished cirrhosis was seen in 12%. This proportion, however, seems to contrast strikingly with the high incidence of alcoholism in cirrhosis of the liver in all those regions of the world where the sale and consumption of alcoholic beverages is an integral part of social and economic life (TABLE 3). For North and South America the average incidence of alcoholism in cirrhosis is now 66%, for Europe 42%. A small number of series from Asia, where alcohol consumption is low or nonexistent, shows an average incidence of only 1 1 % (TABLE 4). A calculation based on 80 clinical and autopsy series comprising a total of 20,000 cases shows that in the Western World an alcohol etiology in cirrhosis of the liver is found in 50% of the cases (TABLE 5). Even in the United Kingdom, where, owing to high taxes imposed on alcoholic beverages since 1 914,128*133 an alcohol etiology had previously played a laudably minor role, alcohol is now of about equal importance with other causeslZ6 or in some areas even the predominant one.’J2*53 If one endeavors to resolve this apparent discrepancy and to study the association between alcohol abuse and cirrhosis, 3 essential points should be kept in mind : (1) Ethanol is an ambivalent molecule that possesses a metabolic and a pharmacologic side. An intake per time unit up to a certain magnitude can effectively be dealt with by several metabolic degradation systems. However, an intake that exceeds the capacity of these systems will result in an elevation of the blood alcohol level, bringing out the pharmacologic or toxic properties of this central nervous
318 citations