Synergistic interaction of D1 and D2 dopamine receptors in the modulation of the reinforcing effect of brain stimulation.
Rats were trained to press a bar for hypothalamic stimulation, and a frequency-response function was plotted. Quinpirole (a selective D2 agonist) facilitated self-stimulation when injected alone but failed to show the facilitatory effect when injected either 1 hr before or 1 hr after injection of SCH 23390 (a D1 antagonist). Injection of reserpine followed by alpha-methyl-p-tyrosine virtually eliminated self-stimulation. Subsequent injection of either SKF 38393 (a D1 agonist) alone or quinpirole alone did not restore self-stimulation, but a combination of quinpirole and SKF 38393 did. The results suggest that a D2 dopamine agonist facilitates the reinforcing effect of brain stimulation only if D1 receptors are activated by endogenous dopamine or by an exogenous agonist.
Nakajima
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Department of Psychology, Dalhousie University, Halifax, Nova Scotia, Canada.
Liu
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Lau
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D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004873:Ergolines / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D008781:Methyltyrosines / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D012653:Self Stimulation / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine
D001552:Benzazepines; D015259:Dopamine Agents; D004873:Ergolines; D008781:Methyltyrosines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D019805:alpha-Methyltyrosine; D014446:Tyrosine 3-Monooxygenase