title: Selective Enhancement of Dopamine Release in the Ventral Pallidum of Methamphetamine-Sensitized Mice.
abstract: Drugs of abuse induce sensitization, which is defined as enhanced response to additional drug following a period of withdrawal. Sensitization occurs in both humans and animal models of drug reinforcement and contributes substantially to the addictive nature of drugs of abuse, because it is thought to represent enhanced motivational wanting for drug. The ventral pallidum, a key member of the reward pathway, contributes to behaviors associated with reward, such as sensitization. Dopamine inputs to the ventral pallidum have not been directly characterized. Here we provide anatomical, neurochemical, and behavioral evidence demonstrating that dopamine terminals in the ventral pallidum contribute to reward in mice. We report subregional differences in dopamine release, measured by ex vivo fast-scan cyclic voltammetry: rostral ventral pallidum exhibits increased dopamine release and uptake compared with caudal ventral pallidum, which is correlated with tissue expression of dopaminergic proteins. We then subjected mice to a methamphetamine-sensitization protocol to investigate the contribution of dopaminergic projections to the region in reward related behavior. Methamphetamine-sensitized animals displayed a 508% and 307% increase in baseline dopamine release in the rostral and caudal ventral pallidum, respectively. Augmented dopamine release in the rostral ventral pallidum was significantly correlated with sensitized locomotor activity. Moreover, this presynaptic dopaminergic plasticity occurred only in the ventral pallidum and not in the ventral or dorsal striatum, suggesting that dopamine release in the ventral pallidum may be integrally important to drug-induced sensitization.
authors: Department of Environmental Health, Rollins School of Public Health, ‡Center for Neurodegenerative Diseases, §Department of Pharmacology, and ∥Department of Neurology, Emory University , Atlanta, Georgia 30322, United States.
authors: Kristen A
authors: KA
authors: Stout
authors: Department of Environmental Health, Rollins School of Public Health, ‡Center for Neurodegenerative Diseases, §Department of Pharmacology, and ∥Department of Neurology, Emory University , Atlanta, Georgia 30322, United States.
authors: Amy R
authors: AR
authors: Dunn
authors: Department of Environmental Health, Rollins School of Public Health, ‡Center for Neurodegenerative Diseases, §Department of Pharmacology, and ∥Department of Neurology, Emory University , Atlanta, Georgia 30322, United States.
authors: Kelly M
authors: KM
authors: Lohr
authors: Department of Environmental Health, Rollins School of Public Health, ‡Center for Neurodegenerative Diseases, §Department of Pharmacology, and ∥Department of Neurology, Emory University , Atlanta, Georgia 30322, United States.
authors: Shawn P
authors: SP
authors: Alter
authors: Department of Environmental Health, Rollins School of Public Health, ‡Center for Neurodegenerative Diseases, §Department of Pharmacology, and ∥Department of Neurology, Emory University , Atlanta, Georgia 30322, United States.
authors: Rachel A
authors: RA
authors: Cliburn
authors: Department of Environmental Health, Rollins School of Public Health, ‡Center for Neurodegenerative Diseases, §Department of Pharmacology, and ∥Department of Neurology, Emory University , Atlanta, Georgia 30322, United States.
authors: Thomas S
authors: TS
authors: Guillot
authors: Department of Environmental Health, Rollins School of Public Health, ‡Center for Neurodegenerative Diseases, §Department of Pharmacology, and ∥Department of Neurology, Emory University , Atlanta, Georgia 30322, United States.
authors: Gary W
authors: GW
authors: Miller
mesh_terms: D019969:Amphetamine-Related Disorders / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D005917:Globus Pallidus / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D008694:Methamphetamine; D004298:Dopamine
keywords: Dopamine; methamphetamine; sensitization; ventral pallidum; voltammetry