Effects of dopaminergic and glutamatergic receptor antagonists on the acquisition and expression of cocaine conditioning place preference.
A balanced conditioning place preference (CPP) paradigm was used to study the role of dopamine D1 and D2 and glutamatergic NMDA and AMPA/kainate receptors on the acquisition and expression of cocaine place conditioning. The D1 receptor antagonist SCH 23390 (0.1-0.2 mg/kg i.p.), administered before cocaine during the training phase, significantly blocked the establishment of place conditioning (acquisition) but had no effect when administered before testing for place preference in the absence of cocaine (expression). Similar results were obtained with the non-competitive NMDA receptor antagonist MK-801 (0.1-0.5 mg/kg i.p.). The D2 receptor antagonist (-)-sulpiride (50-100 mg/kg i.p.) had no effect on either acquisition or expression of cocaine CPP. The AMPA/kainate receptor antagonist DNQX, administered intracerebroventricularly (0.2-3 micrograms/10 microliters), blocked cocaine CPP when given before testing but not when given before cocaine during the training trials. The results suggest that dopaminergic D1 (but not D2) and glutamatergic NMDA receptors are involved in the primary rewarding properties of cocaine (as assessed by the establishment of CPP) whereas the AMPA/kainate receptors are important only for the behaviour elicited by the stimuli previously associated with the drug action (CPP expression). The implications for the treatment of cocaine craving and relapse are discussed.
Cervo
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Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Samanin
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R
D000818:Animals; D001522:Behavior, Animal; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D017447:Receptors, Dopamine D1; C056723:FG 9041; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D013469:Sulpiride; D003042:Cocaine; D004298:Dopamine