The selective dopamine D3 receptor antagonist SB-277011A reduces nicotine-enhanced brain reward and nicotine-paired environmental cue functions.
Increasing evidence suggests that enhanced dopamine (DA) neurotransmission in the nucleus accumbens (NAc) may play a role in mediating the reward and reinforcement produced by addictive drugs and in the attentional processing of drug-associated environmental cues. The meso-accumbens DA system is selectively enriched with DA D3 receptors, a DA receptor subtype increasingly implicated in reward-related brain and behavioural processes. From a variety of evidence, it has been suggested that selective DA D3 receptor antagonism may be a useful pharmacotherapeutic approach for treating addiction. The present experiments tested the efficacy of SB-277011A, a selective DA D3 receptor antagonist, in rat models of nicotine-enhanced electrical brain-stimulation reward (BSR), nicotine-induced conditioned locomotor activity (LMA), and nicotine-induced conditioned place preference (CPP). Nicotine was given subcutaneously within the dose range of 0.25-0.6 mg/kg (nicotine-free base). SB-277011A, given intraperitoneally within the dose range of 1-12 mg/kg, dose-dependently reduced nicotine-enhanced BSR, nicotine-induced conditioned LMA, and nicotine-induced CPP. The results suggest that selective D3 receptor antagonism constitutes a new and promising pharmacotherapeutic approach to the treatment of nicotine dependence.
Pak
Arlene C
AC
Neuropsychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA.
Ashby
Charles R
CR
Heidbreder
Christian A
CA
Pilla
Maria
M
Gilbert
Jeremy
J
Xi
Zheng-Xiong
ZX
Gardner
Eliot L
EL
D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001245:Association Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D003463:Cues; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D012201:Reward; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*
D018492:Dopamine Antagonists; D018722:Nicotinic Agonists; D009570:Nitriles; C409982:SB 277011; D044005:Tetrahydroisoquinolines; D009538:Nicotine