Since cloning of the dopamine receptor D4 (DRD4) its role in the brain has remained unclear. administration of 0.4?mg/kg nicotine R406 (freebase) from vehicle under an FR schedule of food delivery. L-745 870 significantly attenuated reinstatement of nicotine-seeking induced by both nicotine-associated cues and nicotine priming. In contrast L-745 870 did not affect established nicotine self-administration behavior or reinstatement of food-seeking behavior induced by food cues or food priming. L-745 870 did not produce nicotine-like discriminative-stimulus effects and did not alter discriminative-stimulus effects of nicotine. PD 168 77 did not reinstate extinguished nicotine-seeking behavior. As DRD4 blockade by L-745 870 selectively attenuated both cue- and nicotine-induced reinstatement of nicotine-seeking behavior without influencing R406 (freebase) cue- or food-induced reinstatement of food-seeking behavior DRD4 antagonists are potential restorative agents against tobacco smoking relapse. gene is definitely highly polymorphic having a variable quantity of tandem repeats (VNTRs) in exon III (in particular the presence or absence of the 7-repeat (‘long’) allele) and a single-nucleotide polymorphism in the promoter region (C-521T) with both becoming associated with variance in the manifestation of DRD4 decreased ligand binding and attenuation of cyclic adenosine monophosphate (cAMP) formation (Asghari gene smoking practices related to self-medication (ie. smoking to increase arousal or decrease negative affect) were significantly higher when compared with smokers heterozygous or homozygous for the long alleles (Lerman gene have been linked to chronic alcoholism tobacco smoking opioid dependence impulsivity novelty-seeking behavior and attention-deficit hyperactivity disorder (Chien gene has been correlated with smoking and cocaine cue reactivity as well as alcohol- and heroin-craving behavior (Hutchison water and food. After a week of habituation to the colony space animals were singularly housed and diet restricted (～20g/day time) throughout the experiments. All experimental methods described with this study were carried out in compliance with the guidelines of the Canadian Council on Animal Care and/or the guidelines of the Animal Care and Use Committee of the National Institute on Drug Abuse Intramural Research System. (?)Smoking hydrogen tartrate (Sigma-Aldrich St Louis MO USA) was dissolved in saline and the pH of solution was modified to 7.0±0.2. Smoking answer was freshly prepared and filtered through a 0.22-mm syringe filter (Fisher Scientific Pittsburgh PA USA) to minimize the risk of infection. All nicotine doses are described as free base concentrations. Smoking was given i.v. inside a volume of 100?μl/kg per infusion or subcutaneously (s.c.) inside a volume of 1?ml/kg. R406 (freebase) The selective DRD4 antagonist L-745 870 (3-[4-(4-chlorophenyl)piperazin-1-yl]methyl-1access to water. Surgical Procedures for Catheterization into the Jugular Vein After food training rats were surgically implanted with catheters into the right external jugular vein. Surgery was performed under anesthesia induced by xylazine Id1 (10?mg/kg) and ketamine hydrochloride (75?mg/kg). Once anesthetized marcaine was infused into the incision sites and buprenorphine (0.03?mg/kg) was administered s.c. to provide analgesia. Although surgeries were performed using aseptic techniques penicillin was administrated s.c. in one dose of 30?000?Models. The catheter consisted of silastic tubing became a member of to polyethylene tubing which terminated inside R406 (freebase) a threaded nylon connector with an attached piece of medical mesh. The silastic end was put into the jugular vein and the catheter approved s.c. to the dorsal surface between the scapulae where it exited. After surgery animals recovered from anesthesia on a heating pad and a s.c. infusion of ～10?ml/kg sterile isotonic saline was administered for fluid replacement. Animals then experienced a 1-week recovery period before commencement of experimental methods. After recovery from surgery the catheter was flushed daily with saline comprising heparin (0.1?ml 30 and catheter patency was verified by administration of methohexital in the completion of.