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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

Fig. 4.2 Images of [(11)C] cocaine distribution in human brain at different
time points after injection

Source: Fowler et al., 2001. Reproduced with permission of the publisher.
antagonists attenuate cocaine self-administration (Caine & Koob 1994) while
D and D -like receptor agonists maintain cocaine self-administration (as
1 2
reviewed in Platt, Rowlett & Spealman, 2001). Using PET to investigate the
role of dopamine in the reinforcing effects of cocaine in humans it has been
shown that the rate at which cocaine enters the brain and blocks the
dopamine transporter is associated with the “high”, and not merely with the
presence of the drug in the brain (Volkow et al., 1999).
Despite the evidence pointing to a dopaminergic mechanism for cocaine
reward, dopamine may not be the sole mediator of the reinforcing properties
of cocaine, since dopamine transporter knock-out mice – mice that have had
the dopamine transporter gene silenced so that the transporter is not
expressed, (see Chapter 5) – continue to self-administer cocaine (Rocha et
al., 1998). The serotonergic system may influence the reinforcing properties
of cocaine, because cocaine also facilitates serotonin transmission in the
nucleus accumbens (Andrews & Lucki, 2001).

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