Increased occupation of D1 and D2 dopamine receptors accompanies cocaine-induced behavioral sensitization.
In rats exhibiting behavioural sensitization after daily cocaine (10 mg/kg, i.p.) injections, the occupation of D1 and D2 dopamine receptors by dopamine, measured as protection from N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) receptor denaturation, was increased by about 100% compared to animals receiving cocaine in a treatment regimen that produced behavioural tolerance. Co-administration with nimodipine, an agent that blocks the impulse-dependent increase in synaptic concentrations of dopamine caused by cocaine, not only blocked sensitization but also blocked the increase in occupation of receptors. These findings strongly support the hypothesis that enhanced dopamine release and subsequent interaction with dopamine receptors is a substrate for behavioural sensitization to cocaine and have implications for the pharmacotherapy of cocaine abuse.
Burger
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LY
Department of Psychiatry, Mackenzie Health Sciences Centre, University of Alberta, Edmonton, Canada.
Martin-Iverson
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MT
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009553:Nimodipine / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D013134:Spiperone / Q000494:pharmacology
D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D011804:Quinolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013134:Spiperone; D009553:Nimodipine; C000470:EEDQ; D003042:Cocaine