Alcohol dependence, withdrawal, and relapse

Alcohol Research & Health, Winter, 2008 by Howard C. Becker

The development of alcohol dependence is a complex and dynamic process. Many neurobiological and environmental factors influence motivation to drink (Grant 1995; Samson and Hodge 1996; Vengeliene et al. 2008; Weiss 2005). At any given time, an individual's propensity to imbibe is thought to reflect a balance between alcohol's positive reinforcing (i.e., rewarding) effects, such as euphoria and reduction of anxiety (i.e., anxiolysis), and the drug's aversive effects, which typically are associated with negative consequences of alcohol consumption (e.g., hangover or withdrawal symptoms). Memories associated with these rewarding and aversive qualities of alcohol, as well as learned associations between these internal states and related environmental stimuli or contexts, influence both the initiation and regulation of intake. These experiential factors, together with biological and environmental influences and social forces, are central to the formation of expectations about the consequences of alcohol use. These expectations, in turn, shape an individual's decision about engaging in drinking behavior.

The nature of and extent to which these factors are operable in influencing decisions about drinking not only vary from one individual to another but also depend on the stage of addiction--that is, whether the drinker is at the stage of initial experience with alcohol, early problem drinking, or later excessive consumption associated with dependence. Although many people abuse alcohol without meeting the criteria for alcohol dependence (1), continued excessive alcohol consumption can lead to the development of dependence. Neuroadaptive changes that result from continued alcohol use and abuse (which manifest as tolerance and physiological dependence) are thought to be crucial in the transition from controlled alcohol use to more frequent and excessive, uncontrollable drinking (Koob and Le Moal 2008). Indeed, for some dependent individuals, the fear that withdrawal symptoms might emerge if they attempt to stop or significantly curtail drinking may prominently contribute to the perpetuation of alcohol use and abuse.

This article will provide an overview of the basic features of alcohol dependence and the associated withdrawal syndrome, emphasizing those components of withdrawal that especially are thought to contribute to the problem of relapse. It will present evidence from both clinical and experimental studies that highlights long-lasting physiological and emotional changes which are characteristic of dependence and have been postulated to play a key role in persistent vulnerability to relapse. In particular, it will review animal models of alcohol dependence and withdrawal, as well as models of self-administration, that have helped researchers elucidate brain mechanisms underlying relapse and excessive drinking associated with dependence.

ALCOHOL WITHDRAWAL

When an alcohol-dependent individual abruptly terminates or substantially reduces his or her alcohol consumption, a characteristic withdrawal syndrome ensues. In general, alcohol acts to suppress central nervous system (CNS) activity, and, as with other CNS depressants, withdrawal symptoms associated with cessation of chronic alcohol use are opposite in nature to the effects of intoxication. Typical clinical features of alcohol withdrawal include the following (Becker 2000; Hall and Zador 1997; Saitz 1998):

* Signs of heightened autonomic nervous system2 activation, such as rapid heartbeat (i.e., tachycardia), elevated blood pressure, excessive sweating (i.e., diaphoresis), and shaking (i.e., tremor);

* Excessive activity of the CNS (i.e., CNS hyperexcitability) that may culminate in motor seizures; and

* Hallucinations and delirium tremens in the most severe form of withdrawal.

In addition to physical signs of withdrawal, a constellation of symptoms contributing to a state of distress and psychological discomfort constitute a significant component of the withdrawal syndrome (Anton and Becker 1995; Roelofs 1985; Schuckit et al. 1998). These symptoms include emotional changes such as irritability, agitation, anxiety, and dysphoria, as well as sleep disturbances, a sense of inability to experience pleasure (i.e., anhedonia), and frequent complaints about "achiness," which possibly may reflect a reduced threshold for pain sensitivity. Many of these signs and symptoms, including those that reflect a negative-affect state (e.g., anxiety, distress, and anhedonia) also have been demonstrated in animal studies involving various models of dependence (Becker 2000).

Although many physical signs and symptoms of withdrawal typically abate within a few days, symptoms associated with psychological distress and dysphoria may linger for protracted periods of time (Anton and Becker 1995; De Soto et al. 1985; Martinotti et al. 2008). The persistence of these symptoms (e.g., anxiety, negative affect, altered reward set point manifesting as dysphoria and/or anhedonia) may constitute a significant motivational factor that leads to relapse to heavy drinking.