title: D3 dopamine receptors interact with dopamine D1 but not D4 receptors in the GABAergic terminals of the SNr of the rat.
abstract: The firing rate of substantia nigra reticulata (SNr) neurons is modulated by GABA release from striatonigral and pallidonigral projections. This release is, in turn, modulated by dopamine acting on dopamine D1 receptors at striatonigral terminals and D4 receptors at pallidonigral terminals. In addition, striatal neurons that express D1 receptors also express D3 receptors. In this study we analyzed the possible significance of D3 and D1 receptor colocalization in striatonigral projections. We found that these receptors coprecipitate in SNr synaptosomes suggesting their close association in this structure. D1 agonist SKF 38393 administered alone increased mIPSC frequency in SNr slices and cAMP production in SNr synaptosomes, however, the selective D3 agonist PD 128,907 increased mIPSC frequency and cAMP production only when D1 receptors were concurrently stimulated. The D1 antagonist SCH 23390 blocked completely the effects of the concurrent administration of these agonists while the selective D3 antagonist GR 103691 blocked only the potentiating effects of PD 128,907. These findings further indicate that D1 and D3 receptors are localized in the same structure. The D4 agonist PD 168,077 decreased mIPSCs frequency without changing amplitude, an effect that was blocked by the selective D4 antagonist L 745,870. The effects of D4 receptor stimulation disappeared after lesioning the globus pallidus. D3 agonist PD 128,907 did not reduce mIPSC frequency even in neurons that responded to D4 agonist. In sum, activation of D3 receptors in SNr potentiates the stimulation of transmitter release and cAMP production caused by D1 receptor activation of striatonigral projections while it is without effects in terminals, probably of pallidal origin, that are inhibited by activation of D4 receptors.
authors.affiliation: Department of Pharmacology, CINVESTAV-IPN, Mexico.
authors.forename: Refugio
authors.initials: R
authors.lastname: Cruz-Trujillo
authors.forename: Arturo
authors.initials: A
authors.lastname: Avalos-Fuentes
authors.forename: Claudia
authors.initials: C
authors.lastname: Rangel-Barajas
authors.forename: Francisco
authors.initials: F
authors.lastname: Paz-Bermúdez
authors.forename: Arturo
authors.initials: A
authors.lastname: Sierra
authors.forename: Erick
authors.initials: E
authors.lastname: Escartín-Perez
authors.forename: Jorge
authors.initials: J
authors.lastname: Aceves
authors.forename: David
authors.initials: D
authors.lastname: Erlij
authors.forename: Benjamín
authors.initials: B
authors.lastname: Florán
mesh_terms: D000818:Animals; D018491:Dopamine Agonists / Q000378:metabolism / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D050638:Receptors, Dopamine D4 / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4