Animal Models of the Preoccupation/Anticipation Stage of the Addiction Cycle
Relapse to drugs of abuse commonly occurs even after the physical and motivational signs of withdrawal have subsided, from days to weeks to months to even years later. This suggests that the neurochemical changes that occur during the development of dependence can persist far beyond the overt signs of acute withdrawal end. Animal work has shown that prior dependence lowers an individual’s “dependence threshold.” For example, previously ethanol-dependent animals made dependent again display even more severe withdrawal symptoms than when they received alcohol for the first time (Branchey et al., 1971; Baker and Cannon, 1979; Becker and Hale, 1989; Becker, 1994). Alcohol experience and the development of dependence in particular can lead to long-lasting motivational alterations in responsiveness to alcohol.
Increases in alcohol self-administration that persist long past acute withdrawal and detoxification can be observed in rats that have been made dependent (Roberts et al., 2000). The persistent alterations in ethanol self-administration and residual sensitivity to stressors have been arbitrarily defined as a state of “protracted abstinence” (or prolonged abstinence). Protracted abstinence in the rat begins after the acute physical signs of withdrawal have disappeared, with elevations in ethanol intake over baseline and increased stress responsivity persisting 2–8 weeks after withdrawal from chronic ethanol.
A robust and reliable feature of animal models of alcohol drinking is an increase in consumption after a period of deprivation. This is called the “alcohol deprivation effect” and has been observed in mice, rats, monkeys, and human drinkers.