Neuro-anatomic mapping of dopamine D1 receptor involvement in nicotine self-administration in rats

NEUROPHARMACOLOGY

卷:99

Article

Hall, Brandon J.¹  Slade, Susan¹  Allenby, Cheyenne¹  Kutlu, Munir G.²  Levin, Edward D.¹ 

[1] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA

[2] Temple Univ, Dept Psychol, Neurosci Program, Philadelphia, PA 19122 USA

关键词: Dopamine;    Nucleus accumbens;    Anterior cingulate cortex;    Parietal cortex;    Nicotine;    Self-administration;   

DOI  :  10.1016/j.neuropharm.2015.03.005

来源: Elsevier

【 摘 要 】

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 D-1 and D-2 dopamine receptors in drug addiction and its treatment remain to be fully understood. In this study, we examined the effects of blocking D-1 and D-2 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 D-1 or D-2 antagonists (SCH-23390 or haloperidol) into each targeted brain area. Acute local infusions of SCH-23390 (1-4 mu g/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 mu g/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 D-1 receptor mechanisms in the process of nicotine reinforcement and help provide a more detailed neuroanatomic map of nicotine dependence in the brain. (C) 2015 Elsevier Ltd. All rights reserved.

【 授权许可】

Free