QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (92) Citing Articles via Google Scholar Google Scholar Articles by Tepper, J. M. Articles by Creese, I. Search for Related Content PubMed PubMed Citation Articles by Tepper, J. M. Articles by Creese, I.

 Previous Article  |  Next Article 

Volume 17, Number 7, Issue of April 1, 1997 pp. 2519-2530
Copyright ©1997 Society for Neuroscience

Functional Roles of Dopamine D₂ and D₃ Autoreceptors on Nigrostriatal Neurons Analyzed by Antisense Knockdown In Vivo

Received Nov. 27, 1996; revised Jan. 21, 1997; accepted Jan. 22, 1997.

James M. Tepper, Bao-Cun Sun, Lynn P. Martin, and Ian Creese

Center for Molecular and Behavioral Neuroscience, Aidekman Research Center, Program in Cellular and Molecular Biodynamics, Rutgers, The State University of New Jersey, Newark, New Jersey 07102

Two different 19-mer antisense oligodeoxynucleotides complementary to the initial coding regions of dopamine D₂ or D₃ receptor mRNA were infused unilaterally into the substantia nigra of rats for 3-6 d to suppress synthesis of D₂ and/or D₃ receptors on substantia nigra dopaminergic neurons, thereby producing specific reductions of D₂ and/or D₃ receptors. Autoradiographic receptor binding revealed that D₂ and D₃ antisense oligodeoxynucleotides specifically and significantly reduced D₂ or D₃ binding in the ipsilateral substantia nigra, respectively, without affecting dopamine receptor binding in the neostriatum. Either D₂ or D₃ antisense oligodeoxynucleotides greatly attenuated the ability of apomorphine to inhibit dopaminergic neurons in vivo, an effect that was potentiated by simultaneous administration of D₂ and D₃ antisenses. Despite these effects, neither the rate nor the pattern of spontaneous activity of antisense-treated nigrostriatal neurons differed from those in the control groups. The proportion of antidromic responses consisting of full spikes from antisense-treated rats was significantly greater, and the mean antidromic threshold was significantly lower than in controls, indicating that autoreceptor knockdown increased both somatodendritic and terminal excitability. These data demonstrate that selective reduction of specific dopamine receptor subtypes by antisense infusion can be effected in vivo, and that nigrostriatal neurons express both D₂ and D₃ autoreceptors at their somatodendritic and axon terminal regions. Although the somatodendritic and terminal autoreceptors modulate dendritic and terminal excitability, respectively, the interaction of endogenously released dopamine with somatodendritic autoreceptors does not appear to exert a significant effect on spontaneous activity in anesthetized rats.

Key words: antisense oligodeoxynucleotide; autoreceptor; dopamine receptor subtype; D₂ receptor; D₃ receptor; electrophysiology; substantia nigra

This article has been cited by other articles:

				R. Zhao-Shea, B. N. Cohen, H. Just, T. McClure-Begley, P. Whiteaker, S. R. Grady, O. Salminen, P. D. Gardner, H. A. Lester, and A. R. Tapper Dopamine D2-receptor activation elicits akinesia, rigidity, catalepsy, and tremor in mice expressing hypersensitive {alpha}4 nicotinic receptors via a cholinergic-dependent mechanism FASEB J, January 1, 2010; 24(1): 49 - 57. [Abstract] [Full Text] [PDF]

				D. H. Zald, R. L. Cowan, P. Riccardi, R. M. Baldwin, M. S. Ansari, R. Li, E. S. Shelby, C. E. Smith, M. McHugo, and R. M. Kessler Midbrain Dopamine Receptor Availability Is Inversely Associated with Novelty-Seeking Traits in Humans J. Neurosci., December 31, 2008; 28(53): 14372 - 14378. [Abstract] [Full Text] [PDF]

				A. Zapata, B. Kivell, Y. Han, J. A. Javitch, E. A. Bolan, D. Kuraguntla, V. Jaligam, M. Oz, L. D. Jayanthi, D. J. Samuvel, et al. Regulation of Dopamine Transporter Function and Cell Surface Expression by D3 Dopamine Receptors J. Biol. Chem., December 7, 2007; 282(49): 35842 - 35854. [Abstract] [Full Text] [PDF]

				L. J. Gentet and S. R. Williams Dopamine Gates Action Potential Backpropagation in Midbrain Dopaminergic Neurons J. Neurosci., February 21, 2007; 27(8): 1892 - 1901. [Abstract] [Full Text] [PDF]

				V. Davila, Z. Yan, L. C. Craciun, D. Logothetis, and D. Sulzer D3 Dopamine Autoreceptors Do Not Activate G-Protein-Gated Inwardly Rectifying Potassium Channel Currents in Substantia Nigra Dopamine Neurons J. Neurosci., July 2, 2003; 23(13): 5693 - 5697. [Abstract] [Full Text] [PDF]

				Y. Schmitz, C. Schmauss, and D. Sulzer Altered Dopamine Release and Uptake Kinetics in Mice Lacking D2 Receptors J. Neurosci., September 15, 2002; 22(18): 8002 - 8009. [Abstract] [Full Text] [PDF]

				A. Ricci, S. Marchal-Victorion, E. Bronzetti, A. Parini, F. Amenta, and S. K. Tayebati Dopamine D4 Receptor Expression in Rat Kidney: Evidence for Pre- and Postjunctional Localization J. Histochem. Cytochem., August 1, 2002; 50(8): 1091 - 1096. [Abstract] [Full Text] [PDF]

				W. S. Cobb and E. D. Abercrombie Distinct Roles for Nigral GABA and Glutamate Receptors in the Regulation of Dendritic Dopamine Release under Normal Conditions and in Response to Systemic Haloperidol J. Neurosci., February 15, 2002; 22(4): 1407 - 1413. [Abstract] [Full Text] [PDF]

				G. D. Stanwood, R. P. Artymyshyn, M.-P. Kung, H. F. Kung, I. Lucki, and P. McGonigle Quantitative Autoradiographic Mapping of Rat Brain Dopamine D3 Binding with [125I]7-OH-PIPAT: Evidence for the Presence of D3 Receptors on Dopaminergic and Nondopaminergic Cell Bodies and Terminals J. Pharmacol. Exp. Ther., December 1, 2000; 295(3): 1223 - 1231. [Abstract] [Full Text]

				C. Reavill, S. G. Taylor, M. D. Wood, T. Ashmeade, N. E. Austin, K. Y. Avenell, I. Boyfield, C. L. Branch, J. Cilia, M. C. Coldwell, et al. Pharmacological Actions of a Novel, High-Affinity, and Selective Human Dopamine D3 Receptor Antagonist, SB-277011-A J. Pharmacol. Exp. Ther., September 1, 2000; 294(3): 1154 - 1165. [Abstract] [Full Text]

				C. R. Ashby Jr., Y. Minabe, G. Stemp, J. J. Hagan, and D. N. Middlemiss Acute and Chronic Administration of the Selective D3 Receptor Antagonist SB-277011-A Alters Activity of Midbrain Dopamine Neurons in Rats: An In Vivo Electrophysiological Study J. Pharmacol. Exp. Ther., September 1, 2000; 294(3): 1166 - 1174. [Abstract] [Full Text]

				M. J. Millan, A. Gobert, A. Newman-Tancredi, F. Lejeune, D. Cussac, J.-M. Rivet, V. Audinot, T. Dubuffet, and G. Lavielle S33084, a Novel, Potent, Selective, and Competitive Antagonist at Dopamine D3-Receptors: I. Receptorial, Electrophysiological and Neurochemical Profile Compared with GR218,231 and L741,626 J. Pharmacol. Exp. Ther., June 1, 2000; 293(3): 1048 - 1062. [Abstract] [Full Text]

				M. J. Millan, F. Lejeune, and A. Gobert Reciprocal autoreceptor and heteroreceptor control of serotonergic, dopaminergic and noradrenergic transmission in the frontal cortex: relevance to the actions of antidepressant agents J Psychopharmacol, March 1, 2000; 14(2): 114 - 138. [Abstract] [PDF]

				M. J. Millan, A. Gobert, A. Newman-Tancredi, F. Lejeune, D. Cussac, J.-M. Rivet, V. Audinot, A. Adhumeau, M. Brocco, J.-P. Nicolas, et al. S18327 (1-{2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)piperid-1-yl]ethyl}3-phenyl imidazolin-2-one), a Novel, Potential Antipsychotic Displaying Marked Antagonist Properties at alpha 1- and alpha 2-Adrenergic Receptors: I. Receptorial, Neurochemical, and Electrophysiological Profile J. Pharmacol. Exp. Ther., January 1, 2000; 292(1): 38 - 53. [Abstract] [Full Text]

				Z. D. Ling, H. C. Robie, C. W. Tong, and P. M. Carvey Both the Antioxidant and D3 Agonist Actions of Pramipexole Mediate Its Neuroprotective Actions in Mesencephalic Cultures J. Pharmacol. Exp. Ther., April 1, 1999; 289(1): 202 - 210. [Abstract] [Full Text]

				E. V. Kuzhikandathil and G. S. Oxford Activation of Human D3 Dopamine Receptor Inhibits P/Q-Type Calcium Channels and Secretory Activity in AtT-20 Cells J. Neurosci., March 1, 1999; 19(5): 1698 - 1707. [Abstract] [Full Text] [PDF]

				M. J. Millan, A. Newman-Tancredi, M. Brocco, A. Gobert, F. Lejeune, V. Audinot, J.-M. Rivet, R. Schreiber, A. Dekeyne, M. Spedding, et al. S 18126 ({2-[4-(2,3-dihydrobenzo[1,4]dioxin-6-yl)piperazin-1-yl methyl]indan-2-yl}), a Potent, Selective and Competitive Antagonist at Dopamine D4 Receptors: An In Vitro and In Vivo Comparison with L 745,870 (3-(4-[4-chlorophenyl]piperazin-1-yl)methyl-1H-pyrrolo[2,3b]pyridine) and Raclopride J. Pharmacol. Exp. Ther., October 1, 1998; 287(1): 167 - 186. [Abstract] [Full Text]

				V. Audinot, A. Newman-Tancredi, A. Gobert, J.-M. Rivet, M. Brocco, F. Lejeune, L. Gluck, I. Desposte, K. Bervoets, A. Dekeyne, et al. A Comparative In Vitro and In Vivo Pharmacological Characterization of the Novel Dopamine D3 Receptor Antagonists (+)-S 14297, Nafadotride, GR 103,691 and U 99194 J. Pharmacol. Exp. Ther., October 1, 1998; 287(1): 187 - 197. [Abstract] [Full Text]

				M. J. Millan, A. Gobert, A. Newman-Tancredi, V. Audinot, F. Lejeune, J.-M. Rivet, D. Cussac, J.-P. Nicolas, O. Muller, and G. Lavielle S 16924 ((R)-2-{1-[2-(2,3-Dihydro-Benzo[1,4] Dioxin-5-Yloxy)-Ethyl]-Pyrrolidin-3yl}-1-(4-Fluoro-Phenyl)-Ethanone), a Novel, Potential Antipsychotic with Marked Serotonin (5-HT)1A Agonist Properties: I. Receptorial and Neurochemical Profile in Comparison with Clozapine and Haloperidol J. Pharmacol. Exp. Ther., September 1, 1998; 286(3): 1341 - 1355. [Abstract] [Full Text]

				T. E. Koeltzow, M. Xu, D. C. Cooper, X.-T. Hu, S. Tonegawa, M. E. Wolf, and F. J. White Alterations in Dopamine Release But Not Dopamine Autoreceptor Function in Dopamine D3 Receptor Mutant Mice J. Neurosci., March 15, 1998; 18(6): 2231 - 2238. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help