Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIADA000471-09
Application #
8553245
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2012
Total Cost
$1,731,586
Indirect Cost

  Institution

Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Gigante, Eduardo D; Benaliouad, Faiza; Zamora-Olivencia, Veronica et al. (2016) Optogenetic Activation of a Lateral Hypothalamic-Ventral Tegmental Drive-Reward Pathway. PLoS One 11:e0158885
Stuber, Garret D; Wise, Roy A (2016) Lateral hypothalamic circuits for feeding and reward. Nat Neurosci 19:198-205
Barbano, M Flavia; Wang, Hui-Ling; Morales, Marisela et al. (2016) Feeding and Reward Are Differentially Induced by Activating GABAergic Lateral Hypothalamic Projections to VTA. J Neurosci 36:2975-85
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
You, Zhi-Bing; Wang, Bin; Liu, Qing-Rong et al. (2015) Reciprocal Inhibitory Interactions between the Reward-Related Effects of Leptin and Cocaine. Neuropsychopharmacology :
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

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