title: Neuro-anatomic mapping of dopamine D1 receptor involvement in nicotine self-administration in rats.
abstract: Dopaminergic signaling has long been known to be a critical factor in nicotine addiction, as well as other drugs of abuse. Dopaminergic projections from the VTA to the nucleus accumbens and prefrontal cortex have been well established to be critical to the reinforcing effects of these drugs. However, other projections of dopamine neurons are likely to have significant roles in this process. Also, the relative contributions of D1 and D2 dopamine receptors in drug addiction and its treatment remain to be fully understood. In this study, we examined the effects of blocking D1 and D2 receptors in the nucleus accumbens shell (AcS), anterior cingulate cortex (ACC), and parietal association cortex (PtA) on nicotine self-administration in rats. Female Sprague-Dawley rats were fitted with jugular catheters and allowed to self-administer nicotine (0.03 mg/kg/infusion) on an FR1 schedule. Rats were fitted with bilateral infusion cannulae to allow infusion of D1 or D2 antagonists (SCH-23390 or haloperidol) into each targeted brain area. Acute local infusions of SCH-23390 (1-4 μg/side) into the AcS and PtA significantly reduced nicotine self-administration by up to 75%. SCH-23390 infusion into the ACC was less effective with only suggestive non-significant reductions of nicotine self-administration. Acute, local infusions of haloperidol (0.5-2 μg/side) in any of the brain regions targeted did not have significant effects on nicotine self-administration. These results demonstrate a more significant role for D1 receptor mechanisms in the process of nicotine reinforcement and help provide a more detailed neuroanatomic map of nicotine dependence in the brain.
authors: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, USA.
authors: Brandon J
authors: BJ
authors: Hall
authors: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, USA.
authors: Susan
authors: S
authors: Slade
authors: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, USA.
authors: Cheyenne
authors: C
authors: Allenby
authors: Department of Psychology, Neuroscience Program, Temple University, USA.
authors: Munir G
authors: MG
authors: Kutlu
authors: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, USA. Electronic address: edlevin@duke.edu.
authors: Edward D
authors: ED
authors: Levin
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001931:Brain Mapping; D002408:Catheters, Indwelling; D015331:Cohort Studies; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage; D018722:Nicotinic Agonists / Q000008:administration & dosage; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012646:Self Administration; D014029:Tobacco Use Disorder / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D001552:Benzazepines; C000607792:DRD2 protein, rat; D018492:Dopamine Antagonists; D018722:Nicotinic Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D009538:Nicotine; D006220:Haloperidol
keywords: Anterior cingulate cortex; Dopamine; Nicotine; Nucleus accumbens; Parietal cortex; Self-administration