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When D<jats:sub>1<\/jats:sub> receptor stimulation is enhanced by administration of selective D<jats:sub>1<\/jats:sub> receptor agonists, the functional effects of selective D<jats:sub>2<\/jats:sub> agonists are markedly increased. These qualitative and quantitative forms of D<jats:sub>1<\/jats:sub>\/D<jats:sub>2<\/jats:sub> DA receptor synergism are abolished by chronic DA depletion when both D<jats:sub>1<\/jats:sub> and D<jats:sub>2<\/jats:sub> DA receptors are supersensitive. Using both electrophysiological and behavioral methods, the present study examined the effects of selective D<jats:sub>1<\/jats:sub> and D<jats:sub>2<\/jats:sub> renaptnr supersensitivity, induced by repeated administration of selective D<jats:sub>1<\/jats:sub> or D<jats:sub>2<\/jats:sub> receptor antagonists, on the synergistic relationships between D<jats:sub>1<\/jats:sub> and D<jats:sub>2<\/jats:sub> receptors. Daily administration of the selective D<jats:sub>2<\/jats:sub> antagonist eticlopride (0.5 mg\/kg, s.c.) for 3 weeks produced a selective supersensitivity of both dorsal (caudate\u2010putamen) and ventral (nucleus accumbens) striatal neurons to the inhibitory effects of the D<jats:sub>2<\/jats:sub> agonist quinpirole (applied by microiontophoresis). This treatment also abolished the normal ability of the D<jats:sub>1<\/jats:sub> agonist SKF 38393 to potentiate quinpirole\u2010induced inhibition, and relieved D<jats:sub>2<\/jats:sub> receptors from the necessity of D<jats:sub>1<\/jats:sub> receptor stimulation by endogenous DA (enabling), as indicated by significant electrophysiological and behavioral (sterotypy) effects of quinpirole in eticlopride\u2010pretreated, but not saline\u2010pretreated, rats that were also acutely depleted of DA. Daily administration of the selective D<jats:sub>1<\/jats:sub> receptor antagonist SCH 23390 (0.5 mg\/kg, s.c.) caused supersensitivity of striatal neurons to the inhibitory effects of SKF 38393 and also abolished both the ability of SKF 38393 to potentiate quinpirole\u2010induced inhibition and the necessity of D<jats:sub>1<\/jats:sub> receptor stimulation for such inhibition. However, both quinpirole\u2010induced inhibition of striatal cells and stereotyped responses were also somewhat enhanced in SCH 23390\u2010pretreated rats. When such Dl\u2010sensitized rats were acutely depleted of DA, the behavioral effects of quinpirole were intermediate between saline\u2010pretreated rats with acute DA depletion and SCH 23390\u2010pretreated rats without acute DA depletion. Based upon these and related results, it is argued that the enhanced effects of quinpirole in D<jats:sub>1<\/jats:sub>\u2010sensitized rats are due to a heterologous sensitization of D<jats:sub>2<\/jats:sub> receptors rather than to enhanced enabling resulting from supersensitive D<jats:sub>1<\/jats:sub> receptors. It is suggested that supersensitivity of either D<jats:sub>1<\/jats:sub> or D<jats:sub>2<\/jats:sub> receptors can lead to an uncoupling of normal qualitative and quantitative D<jats:sub>1<\/jats:sub>\/D<jats:sub>2<\/jats:sub> synergisms and that the heterologous regulation of D<jats:sub>2<\/jats:sub> receptor sensitivity by D<jats:sub>1<\/jats:sub> receptors may be related to uncoupling of functional D<jats:sub>1<\/jats:sub>\/D<jats:sub>2<\/jats:sub> synergisms.<\/jats:p>","DOI":"10.1002\/syn.890170106","type":"journal-article","created":{"date-parts":[[2004,12,31]],"date-time":"2004-12-31T22:19:57Z","timestamp":1104531597000},"page":"43-61","source":"Crossref","is-referenced-by-count":30,"title":["Loss of D<sub>1<\/sub>\/D<sub>2<\/sub> dopamine receptor synergisms following repeated administration of D<sub>1<\/sub> or D<sub>2<\/sub> receptor selective antagonists: Electrophysiological and behavioral studies"],"prefix":"10.1002","volume":"17","author":[{"given":"Xiu\u2010Ti","family":"Hu","sequence":"first","affiliation":[]},{"given":"Francis J.","family":"White","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2004,10,12]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(92)90753-T"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(85)90345-0"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(85)90541-7"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(87)90144-0"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/347386a0"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)91348-K"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)91368-1"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(86)90588-1"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(85)90349-8"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(88)90156-6"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(87)90619-6"},{"key":"e_1_2_1_13_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.3758\/BF03327175","article-title":"Potentiation of reward\u2010related responding by psychostimulant infusion into nucleus accumbens: Role of dopamine receptor subtypes","volume":"20","author":"Chu B.","year":"1992","journal-title":"Psychobiology"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.890010408"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(85)90549-7"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00422974"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(79)90184-5"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00181952"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00508341"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)90831-7"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(88)90750-9"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(90)94802-5"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(88)90481-9"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.15.030192.001441"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.113050"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)90439-I"},{"key":"e_1_2_1_27_1","first-page":"882","article-title":"Repeated cocaine administration causes a persistent enhancement of D1 dopamine receptor supersensitivity within the rat nucleus accumbens","volume":"258","author":"Henry D. 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