Effects of N-methyl-D-aspartate receptor antagonists on reinstatement of cocaine-seeking behavior by priming injections of cocaine or exposures to cocaine-associated cues in rats.
The reinstatement of extinguished cocaine self-administration behavior was studied in rats pretreated with N-methyl-D-aspartate receptor antagonists. Rats were trained to self-administer intravenous cocaine (0.32 mg/kg/infusion) during five consecutive daily sessions that were followed by five consecutive daily extinction sessions, during which cocaine was unavailable and cocaine-associated cues (sound and light) were absent. Neither the competitive N-methyl-D-aspartate receptor antagonist D-CPPene (0.3-3 mg/kg) nor the low-affinity N-methyl-D-aspartate receptor channel blocker memantine (1-10 mg/kg) reinstated extinguished responding. Priming injections of intravenous cocaine (Experiment 1), and exposures to cocaine-associated stimuli (buzzer and light; Experiment 2) engendered responding on the reinforced lever in excess of that on the non-reinforced lever. In Experiment 1, administration of D-CPPene or memantine prior to the priming injection of cocaine eliminated the difference between reinforced-lever and non-reinforced-lever response rates. For both D-CPPene and memantine, however, this effect was largely due to increased responding upon the non-reinforced lever rather than to decreased reinforced-lever responding. In Experiment 2, D-CPPene, but not memantine, abolished in a dose-dependent manner the selective increase in reinforced-lever over non-reinforced-lever responding that was induced by exposures to cocaine-related stimuli. This effect of D-CPPene was not due to increased non-reinforced-lever responding. These data help define the boundaries within which N-methyl-D-aspartate receptor antagonists can prevent reinstatement of cocaine-seeking behavior (e.g. type of antagonist used and reinstatement procedure).
Bespalov
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AY
Department of Psychopharmacology, Institute of Pharmacology, Pavlov Medical University, St Petersburg, Russia.
Zvartau
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EE
Balster
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RL
Beardsley
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PM
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D008559:Memantine / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012646:Self Administration
D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C065286:SDZ EAA 494; D003042:Cocaine; D008559:Memantine