The selective dopamine D3 receptor antagonist SB 277011-A, but not the partial agonist BP 897, blocks cue-induced reinstatement of nicotine-seeking.
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.
Khaled
Maram A T M
MA
Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, Toronto, Canada.
Farid Araki
Keyghobad
K
Li
Beth
B
Coen
Kathleen M
KM
Marinelli
Peter W
PW
Varga
Jenô
J
Gaál
József
J
Le Foll
Bernard
B
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D054333:Drug Partial Agonism; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology* / Q000627:therapeutic use; D010879:Piperazines / Q000819:agonists / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D020318:Rats, Long-Evans; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors; D012055:Reinforcement Schedule; D012646:Self Administration; D044005:Tetrahydroisoquinolines / Q000494:pharmacology* / Q000627:therapeutic use; D014029:Tobacco Use Disorder / Q000188:drug therapy
D018722:Nicotinic Agonists; D009570:Nitriles; D010879:Piperazines; D050637:Receptors, Dopamine D3; C409982:SB 277011; D044005:Tetrahydroisoquinolines; C120565:BP 897; D009538:Nicotine