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.

Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2013
Total Cost
$1,962,393
Indirect Cost
Name
National Institute on Drug Abuse
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Type
DUNS #
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Stuber, Garret D; Wise, Roy A (2016) Lateral hypothalamic circuits for feeding and reward. Nat Neurosci 19:198-205
You, Zhi-Bing; Wang, Bin; Liu, Qing-Rong et al. (2015) Reciprocal Inhibitory Interactions between the Reward-Related Effects of Leptin and Cocaine. Neuropsychopharmacology :
Steidl, Stephan; Cardiff, Katherine M; Wise, Roy A (2015) Increased latencies to initiate cocaine self-administration following laterodorsal tegmental nucleus lesions. Behav Brain Res 287:82-8
Steidl, S; Myal, S; Wise, R A (2015) Supplemental morphine infusion into the posterior ventral tegmentum extends the satiating effects of self-administered intravenous heroin. Pharmacol Biochem Behav 134:1-5
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
Wise, Roy A; Koob, George F (2014) The development and maintenance of drug addiction. Neuropsychopharmacology 39:254-62
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
Suto, Nobuyoshi; Elmer, Greg I; Wang, Bin et al. (2013) Bidirectional modulation of cocaine expectancy by phasic glutamate fluctuations in the nucleus accumbens. J Neurosci 33:9050-5
Wang, Bin; You, Zhi-Bing; Oleson, Erik B et al. (2013) Conditioned contribution of peripheral cocaine actions to cocaine reward and cocaine-seeking. Neuropsychopharmacology 38:1763-9

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