Blockade of D1 dopamine receptors in the ventral tegmental area decreases cocaine reward: possible role for dendritically released dopamine.
This study was designed to assess the involvement of D1 dopamine actions in the ventral tegmental area (VTA) on intravenous cocaine self-administration. Rats were trained to self-administer intravenous injections of cocaine (1.0 mg/kg per injection) on a fixed-ratio 1 (FR-1) schedule or a progressive ratio (PR) schedule of reinforcement and then were tested under the influence of bilateral VTA injections of the D1 dopamine receptor antagonist SCH 23390 or the 5-HT2 receptor antagonist ketanserin. SCH 23390 increased cocaine self-administration on the FR-1 schedule but decreased it on the PR schedule. Injections of ketanserin were ineffective, as were injections of SCH 23390 in a site 1 mm dorsal or 1 mm rostral to the effective VTA site. These data suggest a role for dendritically released dopamine, presumably acting through D1 receptors located on the axons of GABAergic or glutamatergic inputs to the VTA, in the effectiveness of cocaine reward.
Ranaldi
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Department of Psychology, Queens College, City University of New York, Flushing, New York 11367, USA. Robert_Ranaldi@qc.edu
Wise
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D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004336:Drug Antagonism; D004357:Drug Synergism; D007650:Ketanserin / Q000008:administration & dosage; D008297:Male; D008845:Microinjections; D051381:Rats; D020318:Rats, Long-Evans; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012054:Reinforcement, Psychology; D012201:Reward; D012646:Self Administration; D012702:Serotonin Antagonists / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D012702:Serotonin Antagonists; D007650:Ketanserin; D003042:Cocaine; D004298:Dopamine