Evidence for involvement of both D1 and D2 receptors in maintaining cocaine self-administration.
Rats trained to self-administer cocaine (0.75 mg/kg/infusion) on an FR-5 schedule were treated with selective D1 or D2 antagonists. A69045, a D1 antagonist with no appreciable affinity for 5-HT receptors increased cocaine self-administration to 147, 172 and 167% of baseline at doses of 2.5, 5.0 or 10.0 mumol/kg, SC respectively. SCH-23390 (0.007, 0.015 and 0.030 mumol/kg, SC) increased self-administration to 116, 147 and 165% of baseline, respectively. Both D1 antagonists decreased responding in some animals at the highest dose tested. The D2 antagonist YM-09151-2 showed a similar profile, increasing cocaine self-administration at 0.01 and 0.016 mumol/kg, SC and suppressing responding by most animals at the dose of 0.03 mumol/kg, SC. These data give further support to the hypothesis that both D1 and D2 receptors are involved in maintaining cocaine self-administration.
Abbott Laboratories, Abbott Park, IL 60064.
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Britton
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Curzon
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Mackenzie
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Kebabian
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Williams
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D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D018492:Dopamine Antagonists; D066298:In Vitro Techniques; D008297:Male; D010208:Papaverine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000378:metabolism; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012055:Reinforcement Schedule; D012646:Self Administration / Q000523:psychology; D044005:Tetrahydroisoquinolines
D014150:Antipsychotic Agents; D001549:Benzamides; D001552:Benzazepines; D018492:Dopamine Antagonists; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D044005:Tetrahydroisoquinolines; C061450:A 69024; D010208:Papaverine; D003042:Cocaine; C030265:nemonapride