Multiple Roles for Dopamine in Addictive Behavior

Abstract

Phillips et al. used electrochemical technology to measure moment-to-moment changes in extracellular dopamine concentration in rat nucleus accumbens and discovered that dopamine increased simultaneously with the initiation of drug-seeking behavior. Behaviors that are followed by "rewards"--pleasurable stimuli--tend to be repeated: The behavior is reinforced by the reward. The neurotransmitter dopamine, which is released in response to many pleasurable stimuli, including food, sexual arousal, and many drugs of abuse, is itself powerfully reinforcing: Laboratory animals press levers incessantly in order to obtain a dopamine reward in the appropriate brain regions. Environmental cues that become associated with rewards can themselves trigger reward-seeking behavior, but the neurochemical substrates involved have been less clear (see the News and Views by Self). Phillips et al. implanted carbon-fiber microelectrodes in the nucleus accumbens of rats trained to press levers for cocaine and measured dopamine concentration at 100-ms intervals. Transient increases in dopamine occurred both before and after the lever press. Audiovisual cues that had been associated with cocaine delivery elicited dopamine release when presented in the absence of either a lever press or dopamine. When the experimenters elicited dopamine release through electrical stimulation, the rats responded with drug-seeking behaviors. Thus, dopamine not only mediates behavioral reinforcement, but also plays a key role in the initiation of reward-seeking behaviors in response to environmental cues. Self discusses the implications of this research in the context of associative conditioning and human addiction. P. E. M. Phillips, G. D. Stuber, M. L. A. V. Heien, R. M. Wightman, R. M. Carelli, Subsecond dopamine release promotes cocaine seeking. Nature 422 , 614-618 (2003). [Online Journal] D. Self, Dopamine as chicken and egg. Nature 422 , 573-574 (2003). [Online Journal]