Modeling Sensitization to Stimulants in Humans

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Abstract
Altered dopamine neurotransmission is believed to play a critical role in the pathogenesis of psychosis and addiction.1,2 The phenomenon of sensitization that occurs in the midbrain dopamine system when animals are repeatedly exposed to stimulant drugs may help us understand how dopamine neurotransmission becomes dysregulated. Repeated exposure to stimulant drugs or stress results in heightened behavioral and neurochemical responses after reexposure.3-5 It is generally believed that during the induction of sensitization, the repeated stimulation of dopamine receptors in the ventral tegmental area triggers a cascade of molecular events and changes in neuronal plasticity that, in turn, foster augmented dopamine release.6 In experimental animals, behavioral sensitization is an enduring,7,8 time-dependent3 and context-dependent9 phenomenon that is associated with a long-lasting increase in drug-induced dopaminergic neurotransmission in the striatum.3,10-12 Sensitization is reported to cross-react with stress5 and is variable across individuals.13 A high locomotor response to novel environments predicts the development of sensitization in rats.13