Neuroadaptational Views of Addiction

Behavioral Sensitization

Repeated exposure to many drugs of abuse results in progressive and enduring enhancement of the motor stimulant effect elicited by subsequent exposure to the drug. This phenomenon of behavioral sensitization was hypothesized to underlie some aspects of the neuroplasticity of drug addiction (for further reading, see Vanderschuren and Kalivas, 2000; Robinson and Berridge, 1993). Behavioral or psychomotor sensitization, defined as increased locomotor activation produced by repeated administration of a drug, is more likely to occur with intermittent drug exposure, whereas tolerance is more likely to occur with continuous exposure. Sensitization may also grow with the passage of time. Stress and stimulant sensitization show cross-sensitization. This phenomenon was observed and characterized in the 1970s and 1980s for various drugs and helped identify some of the early neuroadaptations and neuroplasticity associated with repeated drug administration that can lead to substance use disorders. Psychomotor sensitization was invariably linked to sensitization of the activity of the mesolimbic dopamine system.

The conceptualization of a role for psychomotor sensitization in drug addiction was proposed, in which a shift in an incentive salience state, described as wanting (as opposed to liking), progressively increases with repeated drug exposure. Pathologically strong wanting or craving was proposed to define compulsive use. This theory also stated that there is no causal relationship between the subjective pleasurable effects of the drug (drug liking) and the motivation to take it (drug wanting). The systems of the brain that are sensitized were argued to mediate a subcomponent of reward, termed incentive salience (that is, the motivation to take the drug or drug wanting), rather than the pleasurable or euphoric effects of drugs. The psychological process of incentive salience was theorized to be responsible for instrumental drug seeking and drug taking behavior (wanting). This sensitized incentive salience process then produces compulsive patterns of drug use. Through associative learning, the enhanced incentive value becomes oriented specifically toward drug-related stimuli, leading to escalated drug seeking and taking. This theory further argued that the underlying sensitization of neural structures persists, making individuals with addiction vulnerable to long-term relapse. As detailed as this theory is in terms of its attempts to explain the transition from initial drug use to compulsive use, it has been undermined by multiple scientific observations. Individuals with addiction invariably show tolerance to the rewarding effects of drugs of abuse – not sensitization. Animal models of compulsive-like responses to drugs also show tolerance, not sensitization, and millions of individuals take psychostimulants as medications for ADHD; they do not show sensitization. Nonetheless, the one redeeming feature of the sensitization model is its focus on the incentive salience of drugs, which has both empirical and conceptual merit but may involve other mechanisms than those reflected in behavioral (locomotor) sensitization as outlined by the Robinson and Berridge theory.

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