title: Effects of individual and concurrent stimulation of striatal D1 and D2 dopamine receptors on electrophysiological and behavioral output from rat basal ganglia.
abstract: Bilateral infusions of d-amphetamine into the rat ventral-lateral striatum (VLS) were previously shown to cause a robust behavioral activation that was correlated temporally with a net increase in firing of substantia nigra pars reticulata (SNpr) neurons, a response opposite predictions of the basal ganglia model. The current studies assessed the individual and cooperative contributions of striatal D1 and D2 dopamine receptors to these responses. Bilateral infusions into VLS of the D1/D2 agonist apomorphine (10 microg/microl/side) caused intense oral movements and sniffing, and an overall increase in SNpr cell firing to 133% of basal rates, similar to effects of d-amphetamine. However, when striatal D2 receptors were stimulated selectively by infusions of quinpirole (30 microg/microl/side) + the D1 antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390; 10 microg/microl/side), no behavioral response and only modest and variable changes in SNpr cell firing were observed. Selective stimulation of striatal D1 receptors by (+/-) 6-chloro-APB hydrobromide (SKF 82958; 10 microg/microl/side) + the D2 antagonist cis-N-(1-benzyl-2-methyl-pyrrolidin-3-yl)-5-chloro-2-methoxy-4-methyl-aminobenzamide (YM 09151-2; 2 microg/microl/side) caused a weak but sustained increase in oral movements and modestly increased SNpr cell firing, but neither response was of the magnitude observed with apomorphine. When the two agonists were infused concurrently, however, robust oral movements and sniffing again occurred over the same time period that a majority of SNpr cells exhibited marked, sometimes extreme and fluctuating, changes in firing (net increase, 117% of basal rates). These data confirm that concurrent striatal D1/D2 receptor stimulation elicits a strong motor activation that is correlated temporally with a net excitation rather than inhibition of SNpr firing, and reveal that D1 and D2 receptors interact synergistically within the striatum to stimulate both forms of output.
authors.affiliation: Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, USA. b.waszczak@neu.edu
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Waszczak
authors.forename: Lynn P
authors.initials: LP
authors.lastname: Martin
authors.forename: Heather E
authors.initials: HE
authors.lastname: Finlay
authors.forename: Natalie
authors.initials: N
authors.lastname: Zahr
authors.forename: James R
authors.initials: JR
authors.lastname: Stellar
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage / Q000494:pharmacology; D001479:Basal Ganglia / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D004594:Electrophysiology; D005110:Extracellular Space / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008845:Microinjections; D019257:Quinpirole / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology
chemical_list: D001549:Benzamides; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; C071262:SK&F 82958; D001058:Apomorphine; C030265:nemonapride