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      The selective dopamine D3 receptor antagonist SB 277011-A, but not the partial agonist BP 897, blocks cue-induced reinstatement of nicotine-seeking.

      The International Journal of Neuropsychopharmacology
      Animals, Conditioning, Operant, drug effects, Cues, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Interactions, Drug Partial Agonism, Male, Nicotine, administration & dosage, pharmacology, Nicotinic Agonists, Nitriles, therapeutic use, Piperazines, agonists, Rats, Rats, Long-Evans, Receptors, Dopamine D3, antagonists & inhibitors, Reinforcement Schedule, Self Administration, Tetrahydroisoquinolines, Tobacco Use Disorder, drug therapy

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          The dopamine D3 receptor (DRD3) has been suggested to be involved in the mechanisms underlying stimulus-controlled drug-seeking behaviour. Ligands acting as DRD3 antagonists (SB 277011-A) or DRD3 partial agonists (BP 897) have shown some promise for reducing the influence of drug-associated cues on motivational behaviour. Here, effects of SB 277011-A and BP 897 were evaluated on cue-induced reinstatement of nicotine-seeking in rats. The effects of BP 897 on nicotine self-administration under a fixed-ratio 5 (FR5) schedule of reinforcement were also evaluated. SB 277011-A (1-10 mg/kg) was able to block cue-induced reinstatement of nicotine-seeking, indicating that DRD3 selective antagonism may be an effective approach to prevent relapse for nicotine. In contrast, BP 897 did not block the cue-induced reinstatement of nicotine-seeking or nicotine-taking under the FR5 schedule. In a control study, rats did not respond to the light stimuli without nicotine delivery, indicating that the responding for the drug-associated cues was induced by the previous pairing of light stimuli with nicotine's effects. These findings validate the role of DRD3 on reactivity to drug-associated stimuli and suggest that the DRD3 antagonist, but perhaps not the DRD3 partial agonist, could be used to prevent relapse in tobacco smokers.

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