Conditioned and sensitized dopamine transmission: environment-dependent plasticity in human brain

Abstract

BACKGROUND: In laboratory animals the best studied form of neuroplasticity related to drug addiction is the development of conditioned and sensitized dopamine responses. The evidence that these phenomena occur in humans, though, has been sparse.

METHODS: The positron emission tomography (PET) [¹¹C]raclopride method was used to measure striatal dopamine release in subjects with and without a history of stimulant drug use.

RESULTS: The acute administration of the psychostimulant drugs, d-amphetamine (0.3 mg/kg, p.o.) and cocaine (1.0 mg/kg, i.n.) increased extracellular dopamine levels in the ventral limbic striatum. Following repeated amphetamine administration, dopamine responses to drug and stress challenges were significantly greater. When subjects were returned to the now drug-paired PET Unit and administered a placebo capsule, this too was now able to elicit dopamine release. Finally, when experienced stimulant drug abusers were administered drug in the presence of drug cues, lifetime histories of stimulant drug use were positively correlated with the dopamine response, an association that was not seen when the drug was administered in the absence of drug cues.

DISCUSSION: The results suggest that repeated drug exposure can produce (i) conditioned, sensitized, and cross-sensitized dopamine responses, and (ii) dopamine system reactivity can come under progressively greater control of drug-paired cues. Together, these findings provide compelling evidence of experience-dependent plasticity within the human brain. The specific changes might be related to those that – in vulnerable individuals – foster the acquisition of drug-taking behavior and produce a progressive narrowing of interests, providing one pathway to addiction.