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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National Institute on Drug Abuse
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Wise, Roy A; Koob, George F (2014) The development and maintenance of drug addiction. Neuropsychopharmacology 39:254-62
Steidl, Stephan; Wang, Huiling; Wise, Roy A (2014) Lesions of cholinergic pedunculopontine tegmental nucleus neurons fail to affect cocaine or heroin self-administration or conditioned place preference in rats. PLoS One 9:e84412
Kramar, Cecilia P; Chefer, Vladimir I; Wise, Roy A et al. (2014) Dopamine in the dorsal hippocampus impairs the late consolidation of cocaine-associated memory. Neuropsychopharmacology 39:1645-53
Wise, Roy A (2013) Dual roles of dopamine in food and drug seeking: the drive-reward paradox. Biol Psychiatry 73:819-26
Luo, Alice H; Tahsili-Fahadan, Pouya; Wise, Roy A et al. (2011) Linking context with reward: a functional circuit from hippocampal CA3 to ventral tegmental area. Science 333:353-7
Wang, Bin; You, Zhi-Bing; Wise, Roy A (2009) Reinstatement of cocaine seeking by hypocretin (orexin) in the ventral tegmental area: independence from the local corticotropin-releasing factor network. Biol Psychiatry 65:857-62
Suto, Nobuyoshi; Ecke, Laurel E; Wise, Roy A (2009) Control of within-binge cocaine-seeking by dopamine and glutamate in the core of nucleus accumbens. Psychopharmacology (Berl) 205:431-9
Geisler, Stefanie; Wise, Roy A (2008) Functional implications of glutamatergic projections to the ventral tegmental area. Rev Neurosci 19:227-44
Simms, Jeffrey A; Steensland, Pia; Medina, Brian et al. (2008) Intermittent access to 20% ethanol induces high ethanol consumption in Long-Evans and Wistar rats. Alcohol Clin Exp Res 32:1816-23
Wise, Roy A (2008) Dopamine and reward: the anhedonia hypothesis 30 years on. Neurotox Res 14:169-83

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