title: Dopamine dynamics and cocaine sensitivity differ between striosome and matrix compartments of the striatum.
abstract: The striatum is typically classified according to its major output pathways, which consist of dopamine D1 and D2 receptor-expressing neurons. The striatum is also divided into striosome and matrix compartments, based on the differential expression of a number of proteins, including the mu opioid receptor, dopamine transporter (DAT), and Nr4a1 (nuclear receptor subfamily 4, group A, member 1). Numerous functional differences between the striosome and matrix compartments are implicated in dopamine-related neurological disorders including Parkinson's disease and addiction. Using Nr4a1-eGFP mice, we provide evidence that electrically evoked dopamine release differs between the striosome and matrix compartments in a regionally-distinct manner. We further demonstrate that this difference is not due to differences in inhibition of dopamine release by dopamine autoreceptors or nicotinic acetylcholine receptors. Furthermore, cocaine enhanced extracellular dopamine in striosomes to a greater degree than in the matrix and concomitantly inhibited dopamine uptake in the matrix to a greater degree than in striosomes. Importantly, these compartment differences in cocaine sensitivity were limited to the dorsal striatum. These findings demonstrate a level of exquisite microanatomical regulation of dopamine by the DAT in striosomes relative to the matrix.
authors.affiliation: The Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA 22030, USA; Laboratory for Integrative Neuroscience, Section on Synaptic Pharmacology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852, USA.
authors.forename: Armando G
authors.initials: AG
authors.lastname: Salinas
authors.affiliation: Laboratory for Integrative Neuroscience, Section on Synaptic Pharmacology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852, USA.
authors.forename: Margaret I
authors.initials: MI
authors.lastname: Davis
authors.affiliation: Laboratory for Integrative Neuroscience, Section on Synaptic Pharmacology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Lovinger
authors.affiliation: Laboratory for Integrative Neuroscience, Section on Synaptic Pharmacology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852, USA. Electronic address: mateoy@mail.nih.gov.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Mateo
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000096:biosynthesis* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000096:biosynthesis* / Q000378:metabolism; D009924:Organ Culture Techniques; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis*
chemical_list: C000600618:DRD2 protein, mouse; D050483:Dopamine Plasma Membrane Transport Proteins; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D017448:Receptors, Dopamine D2; D003042:Cocaine; D004298:Dopamine
keywords: Dopamine D2 receptor; Dopamine transporter; Nucleus accumbens; Patch; Voltammetry