The dysregulation of brain reward function associated with withdrawal from chronic administration of drugs of abuse is a common element of all drugs of abuse. Withdrawal from chronic cocaine (Markou and Koob, 1991), amphetamine (Paterson et al., 2000), opioids (Schulteis et al., 1994), cannabinoids (Gardner and Vorel, 1998), nicotine (Epping-Jordan et al., 1998), and ethanol (Schulteis et al., 1995) leads to increases in reward threshold during acute abstinence, and some of these elevations in threshold can last for up to one week (Figure 3). These observations lend credence to the hypothesis that opponent processes can set the stage for one aspect of compulsivity where negative reinforcement mechanisms are engaged.
