The habit-forming effects of several addictive drugs have been linked to their ability to elevate levels of the neurotransmitter dopamine in certain brain regions. It is important to determine which other neurotransmitters control the dopamine system and which transmitter systems dopamine controls. Two types of microdialysis studies are employed to identify neurotransmitter fluctuations that accompany drug-seeking behavior or that cause or are caused by fluctuations of dopamine. In the first, microdialysis samples are taken from various brain regions in animals trained to lever-press for intravenous drug injections. In the other, portions of drug-associated brain circuitry are stimulated and subsequent neurotransmitter fluctuations are determined from microdialysis samples distant from the site of stimulation. The results of these studies are integrated to identify the neuronal circuitry of addiction and drug-seeking. Our most recent finding is that the excitatory neurotransmitters glutamate and acetylcholine bring information about reward-associated conditioned stimuli to the dopamine system that responds directly to cocaine. The glutamate input to the dopamine system can be brought under the control of cocaine-predictive cues, including neuronal input responsive to the peripheral effects of cocaine.
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