Excessive Ethanol Drinking Following a History of Dependence Animal Model of Allostasis

Abstract

Self-administration Excessive drinking of ethanol in animals can be produced by a number of factors including altering palatability, genetics, and history of consumption. There is evidence that certain symptoms of withdrawal can persist for a number of weeks or even months following chronic ethanol exposure in humans (Kissin 1979;Begleiter and Porjesz 1979;Alling et al. 1982;Roelofs 1985;Grant et al. 1987) as well as in animals (Begleiter and Porjesz 1979). In human alcoholics, one of the factors leading to excessive drinking is the use of alcohol to relieve or avoid withdrawal symptoms (U.S. Department of Health and Human Services 1990). Fatigue and tension persisted for approximately five weeks following withdrawal in a group of 68 chronic alcoholics (Alling et al. 1982), and periods of hyperventilatory symptomology and anxiety (as determined by the Spielberger State-Trait Anxiety Inventory, a self-report inventory), which correlated with intensity of alcohol craving, were reported for up to nine months following withdrawal in a group of 37 chronic alcoholics (Roelofs 1985).In a larger cohort of 312 abstinent alcoholics, 20-25% of them showed signs of anxiety and depression, as determined from the Symptom Check-List 90 (self-report inventory with coverage of areas of symptomology and psychopathology) six months to two years following withdrawal (De Soto et al. 1985). In a follow-up study, it was shown that distress-related symptoms correlated with relapse in alcoholics who were abstinent for less than two years (De Soto et al. 1989). The more pro- Received March 2, 1999; revised August 25, 1999; accepted December 6, 1999. 582 A.J. Roberts et al. N EUROPSYCHOPHARMACOLOGY 2000 -VOL . 22 , NO . 6 tracted symptoms tended to be subacute, were often affective in nature, and appeared to precede relapses into uncontrolled alcohol drinking. For example, depression and anxiety associated with withdrawal were found to provoke drinking in 83 of 100 male alcoholics who experienced these symptoms (Hershon 1977). These patients reported that they drank alcoholic beverages when they experienced anxiety and depressed mood. In another study, both male and female alcoholics reported negative emotions as the most common trigger of relapse (Annis et al. 1998). The clinical literature suggests that alterations in affective state persist for quite some time following alcohol withdrawal and may actually be partly responsible for some relapse episodes in alcoholics.Potential rodent models of excessive ethanol drinking include the alcohol deprivation effect in nondependent animals, ethanol self-administration in dependent withdrawing animals, and ethanol self-administration in animals with a history of dependence following periods of abstinence. The alcohol deprivation effect is a transient increase in ethanol self-administration in animals following periods of abstinence from ethanol for several days to several weeks (Sinclair and Senter 1967;Spanagel et al. 1996;Heyser et al. 1997;Hölter et al. 1998). This increase in e...

Chronic Ethanol Exposure and Protracted Abstinence Alter NMDA Receptors in Central Amygdala

“…Therefore, we investigated whether or not those changes seen in CeA persisted after prolonged ethanol withdrawal for 1 and 2 weeks. We chose these times because behaviorally they represent a period of protracted abstinence after which voluntary ethanol intake is significantly enhanced (Roberts et al, 2000). The inhibition by acute ethanol of evoked NMDA-EPSCs and NMDA currents were comparable in CeA neurons from naïve and both 1 and 2 week-withdrawn rats, suggesting that the cellular sensitization of NMDARs to ethanol recorded in CET rats had recovered.…”

“…Although dependence is characterized by the appearance of a withdrawal syndrome after cessation of alcohol use, relapse can occur even weeks after withdrawal signs have ceased, suggesting that neuroadaptive changes occurring during dependence can persist beyond the withdrawal period itself. Relapse, that is, a rebound selfadministration, may be maximal at 1-2 weeks during abstinence (Roberts et al, 2000).…”

Conceptual framework for the etiology of alcoholism: a ?kindling?/stress hypothesis

“…However, with ethanol-preferring P-rats, repeated alcohol deprivations increase the magnitude and duration of their response for an alcohol lever . Animals previously physically dependent on alcohol exhibit elevated operant responding for alcohol during withdrawal (Roberts et al 2000) and for an extended period post-withdrawal (Roberts et al 2000;Valdez et al 2002).…”

“…Koob and LeMoal (1997) presented the "hedonic homeostatic dysregulation" hypothesis to explain the adaptation associated with alcoholism. Later, the process of developing alcohol abuse was stated as the "allostasis model of alcoholism" (Koob and LeMoal 2001;Koob 2003a;Roberts et al 2000). This view of "allostasis" arose in part from a previous conceptual framework espoused by Sterling and Eyer (1988) and McEwen (1998McEwen ( , 2000.…”

Drug Addiction, Dysregulation of Reward, and Allostasis

“…Indeed, the dose-effect function appears to shift upward instead of to the right (tolerance) or to the left (sensitization) (Ahmed and Koob 1998). Animals with a history of alcohol dependence show prolonged increases in alcohol self-administration long past acute withdrawal (Roberts et al 2000a). Such changes in drug reward set point may reflect an allostatic change rather than simply sensitization or homeostatic adaptation.…”