Animal Models of the Withdrawal/Negative Affect Stage of the Addiction Cycle

Drug Self-Administration with Extended Access and Drug Self-Administration in Dependent Animals

A progressive increase in the frequency and intensity of drug use is one of the major behavioral phenomena that characterize the development of addiction. Such an escalation has face validity with a number of DSM-IV criteria for addiction, including “Need for markedly increased amounts of substance to achieve intoxication or desired effect,” “Important social, occupational, or recreational activities given up or reduced because of substance use,” “A great deal of time spent in activities necessary to obtain substance, to use substance, or recover from its effects,” and “Substance in larger amounts or over a longer period than the person intended.”

Box 3.1


Notice in this section and throughout the book, we often use the word “-like” to describe behaviors in animals, such as “anxiety-like behavior.” The word anxiety or other such terms are used by people to describe their own subjective internal states; what they themselves are thinking or feeling. When studying animals, however, we cannot ask the rat to report what it is experiencing. Its behavioral or physiological state can be observed by researchers, and such states can bear a striking resemblance to the states observed in people (face validity). Nevertheless, scientists and researchers are discouraged from using anthropomorphisms to describe human-like characteristics in nonhuman organisms. Therefore, we say that such states are like those in humans. We cannot say with absolute certainty that the rat feels “anxious,” but its outward manifestation is objectively close enough to the human condition that we can say it is presenting “anxiety-like” behavior.

A framework with which to model the transition from drug use to drug addiction can be found in relatively recently developed animal models of prolonged access to drug self-administration and drug self-administration in dependent animals during withdrawal (Figure 3.11). Before the extended-access model was developed, rodents were typically given access to the drug for less than 3 h per day, which produced stable and reliable responding for the drug over time. In contrast, in the extended-access model with cocaine, drug access was increased to 6 h per day, which produced dramatic increases in self-administration compared with animals that had the usual 1 h access. This escalation in responding has now been observed with extended access to all major drugs of abuse, including methamphetamine, heroin, nicotine, and alcohol. A similar phenomenon of increased intake is observed when rats are tested repeatedly after the induction of alcohol dependence. They show reliable increases in self-administration after a period of withdrawal, in which the amount of intake can increase 3–4 fold and the animals maintain blood alcohol levels of 100–150 mg% when allowed to self-administer alcohol during withdrawal. In each of these models of extended access, the animals show increased responding on a progressive-ratio schedule when tested during withdrawal, suggesting an increase in reward value or efficacy of the drug when they are dependent.

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