Thus, dependence or manifestation of a withdrawal syndrome after removal of chronic drug administration is defined in terms of motivational aspects of dependence such as emergence of a negative emotional state (e.g., dysphoria, anxiety, irritability) when access to the drug is prevented (Koob and Le Moal, 2001), rather than on the physical signs of dependence. Indeed, some have argued that the development of such a negative affective state can define dependence as it relates to addiction:
