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 what other factors influence the dopamine system. We are currently studying the effects of leptin, a blood-borne hormone that affects reward function and the dopamine system. In order to identify neurotransmitter fluctuations that accompany drug-seeking behavior or that cause or are caused by fluctuations of dopamine, microdialysis samples are taken from various brain regions in animals trained to lever-press for intravenous drug injections. The results of these studies are integrated to identify the neuronal circuitry of addiction and drug-seeking. Our most recent finding is that regular self-administration of intravenous cocaine in rats causes depressions in circulating leptin levels and decreased leptin signaling in the dopamine system. Because leptin modulates the effectiveness of cocaine and cocaine-associated cues we are assessing the leptin system as a potential target for pharmacotherapy for cocaine addiction.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIADA000471-11
Application #
8933819
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2014
Total Cost
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, 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 :
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, 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; Koob, George F (2014) The development and maintenance of drug addiction. Neuropsychopharmacology 39:254-62
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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