Regional distribution of alpha(2C)-adrenoceptors in brain and spinal cord of control mice and transgenic mice overexpressing the alpha(2C)-subtype: an autoradiographic study with [(3)H]RX821002 and [(3)H]rauwolscine.
Behavioral studies on gene-manipulated mice have started to elucidate the neurobiological functions of the alpha(2C)-adrenoceptor (AR) subtype. In this study, we applied quantitative receptor autoradiography to investigate the potential anatomical correlates of the observed functional effects of altered alpha(2C)-AR expression. Labeling of brain and spinal cord sections with the subtype non-selective alpha(2)-AR radioligand [(3)H]RX821002 and the alpha(2C)-AR-preferring ligand [(3)H]rauwolscine revealed distinct binding-site distribution patterns. In control mice, [(3)H]rauwolscine binding was most abundant in the olfactory tubercle, accumbens and caudate putamen nuclei, and in the CA1 field of the hippocampus. A mouse strain with overexpression of alpha(2C)-AR regulated by a gene-specific promoter showed approximately two- to four-fold increased levels of [(3)H]rauwolscine binding in these regions. In addition, dramatic increases in [(3)H]rauwolscine binding were seen in the nerve layer of the olfactory bulb, the molecular layer of the cerebellum, and the ventricular system of alpha(2C)-AR-overexpressing mice, representing "ectopic" alpha(2C)-AR expression. Competition-binding experiments with several alpha(2)-AR ligands confirmed the alpha(2C)-AR identity of these sites. Our results provide quantitative evidence of the predominance of the alpha(2A)-AR subtype in most regions of the mouse CNS, but also disclose the wide distribution of alpha(2C)-AR in the normal mouse brain, although at relatively low density, except in the ventral and dorsal striatum and the hippocampal CA1 area. alpha(2C)-AR are thus present in brain regions involved in the processing of sensory information and in the control of motor and emotion-related activities such as the accumbens and caudate putamen nuclei, the olfactory tubercle, the lateral septum, the hippocampus, the amygdala, and the frontal and somatosensory cortices. The current results may help in specifying an anatomical framework for the functional roles of the alpha(2A)- and alpha(2C)-AR subtypes in the mouse CNS.
Holmberg
M
M
Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520, Turku, Finland.
Fagerholm
V
V
Scheinin
M
M
D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D005260:Female; D019329:Idazoxan / Q000031:analogs & derivatives; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D011869:Radioligand Assay; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics; D014316:Tritium; D015854:Up-Regulation / Q000235:genetics*; D015016:Yohimbine
C547769:Adra2a protein, mouse; C547775:Adra2c protein, mouse; D000317:Adrenergic alpha-Antagonists; D018341:Receptors, Adrenergic, alpha-2; D014316:Tritium; D015016:Yohimbine; C058525:2-methoxyidazoxan; D009638:Norepinephrine; D019329:Idazoxan