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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

motivational value to stimuli that predict drug availability and act as powerful
incentives of drug-seeking behaviour.
Because psychoactive drugs have strongly reinforcing properties, and
because these reinforcing properties can increase the motivational value of
drugs and drug-associated stimuli (e.g. environments where drugs are taken,
the presence of drug dealers or drug users, the sight of drug paraphernalia)
through repeated pairings, the incentive-motivational responding towards
drugs and drug-associated stimuli is increased. (Wikler, 1973; Goldberg, 1976;
Stewart, de Wit & Eikelboom, 1984; Childress et al., 1988; O’Brien et al., 1992;
Robinson & Berridge, 1993; Di Chiara, 1998). Thus, the drug is used, it has
rewarding effects, and this reinforces the drug-using behaviour and associated
stimuli. The question is then: why are psychoactive substances such powerful
reinforcers that they can lead to the development of dependence?

Drug dependence as a response to drug withdrawal

In addition to understanding drug dependence in terms of incentive theories,
it can also be seen as a response to withdrawal reactions. Early theories of
drug dependence, for example, placed major emphasis on the physical effects
of withdrawal as a factor of drug dependence (Himmelsbach, 1943). In this
regard, the adverse physical consequences of withdrawing from a drug’s
effects are viewed as a key motivational determinant of sustained drug taking
through negative reinforcement mechanisms (see Fig. 3.3). However, it is
possible to have dependence without withdrawal and withdrawal without
dependence. For example, it is possible to have cocaine or alcohol
dependence, but not to experience withdrawal symptoms between episodes
of use. There can also be withdrawal symptoms in the absence of dependence,
such as following long-term medical use of benzodiazepines or morphine.
These factors are recognized in diagnostic criteria, where withdrawal is not
necessary or sufficient for a diagnosis of dependence (see Chapter 1). For
these reasons, more recent theories of dependence have moved the emphasis
away from physical withdrawal, and towards motivational dependence
produced in part by withdrawal-induced negative moods such as anhedonia
and dysphoria. This state, by a negative reinforcing mechanism, would
maintain drug self-administration because the drug removes the negative
emotional state of withdrawal (Koob et al., 1989, 1997). The advantage of this
modern version over early physical dependence theories is that motivational
dependence has properties that are common to different classes of
psychoactive substances while the properties of physical dependence differ
widely from one class to another.

Dopamine and reinforcement learning
The role of dopamine in response-reinforcement learning is at the root of
current models of instrumental responding (Montague, Dayan & Sejnowski,

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