title: α2A adrenergic receptors highly expressed in mesoprefrontal dopamine neurons.
abstract: α2 adrenoreceptors (α2-ARs) play a key role in the control of noradrenaline and dopamine release in the medial prefrontal cortex (mPFC). Here, using UV-laser microdissection-based quantitative mRNA expression in individual neurons we show that in hTH-GFP rats, a transgenic line exhibiting intense and specific fluorescence in dopaminergic (DA) neurons, α2A adrenoreceptor (α2A-AR) mRNA is expressed at high and low levels in DA cells in the ventral tegmental area (VTA) and substantia nigra compacta (SNc), respectively. Confocal microscopy fluorescence immunohistochemistry revealed that α2A-AR immunoreactivity colocalized with tyrosine hydroxylase (TH) in nearly all DA cells in the VTA and SNc, both in hTH-GFP rats and their wild-type Sprague-Dawley (SD) counterparts. α2A-AR immunoreactivity was also found in DA axonal projections to the mPFC and dorsal caudate in the hTH-GFP and in the anterogradely labeled DA axonal projections from VTA to mPFC in SD rats. Importantly, the α2A-AR immunoreactivity localized in the DA cells of VTA and in their fibers in the mPFC was much higher than that in DA cells of SNc and their fibers in dorsal caudate, respectively. The finding that α2A-ARs are highly expressed in the cell bodies and axons of mesoprefrontal dopaminergic neurons provides a morphological basis to the vast functional evidence that somatodendritic and nerve-terminal α2A-AR receptors control dopaminergic activity and dopamine release in the prefrontal cortex. This finding raises the question whether α2A-ARs might function as autoreceptors in the mesoprefrontal dopaminergic neurons, replacing the lack of D2 autoreceptors.
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy; Center of Excellence "Neurobiology of Addiction", University of Cagliari, 09042 Monserrato, Italy. Electronic address: castelli@unica.it.
authors.forename: M Paola
authors.initials: MP
authors.lastname: Castelli
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, 09126 Cagliari, Italy.
authors.forename: Saturnino
authors.initials: S
authors.lastname: Spiga
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Perra
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Madeddu
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, 09126 Cagliari, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mulas
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy.
authors.forename: M Grazia
authors.initials: MG
authors.lastname: Ennas
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy; Guy Everett Laboratory" University of Cagliari, 09042 Monserrato, Italy.
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Gessa
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000166:cytology / Q000378:metabolism*
chemical_list: C547769:Adra2a protein, mouse; C547770:Adra2a protein, rat; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D049452:Green Fluorescent Proteins; D014446:Tyrosine 3-Monooxygenase
keywords: caudate; dopamine; meso-prefrontal; substantia nigra; ventral tegmental area; α2A adrenoreceptors