Research Report Involvement of rat dopaminergic system of nucleus accumbens in nicotine-induced anxiogenic-like behaviors Mohammad Reza Zarrindast a, b, c, d, e, ⁎ , Solmaz Khalifeh f , Ameneh Rezayof g , Parvin Rostami f , Arash Aghamohammadi Sereshki f , Maryam Zahmatkesh a a Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran b Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran c Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran d School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran e Institute of Cognitive Science Studies (ICSS), Tehran, Iran f Department of Biology, Faculty of Basic Science, Tarbiat Moalem University, Tehran, Iran g Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran ARTICLE INFO ABSTRACT Article history: Accepted 19 April 2012 Available online 26 April 2012 The objective of the present study was to investigate the involvement of dopamine D 1 and D 2 receptors of the nucleus accumbens (NAc) shell in the anxiogenic-like effect of intra-central amygdala (CeA) nicotine administration. Male Wistar rats with cannula implants in the left CeA and the left shell of NAc were submitted to the elevated plus-maze (EPM). Intra-CeA injections of nicotine (1 μg/rat) decreased % open arm time spent (%OAT) but not % open arm entries (%OAE) and locomotor activity, indicating the possibility of an anxiogenic-like response. Intra-NAc injection of D 1 dopamine receptor antagonist, SCH23390 (0.5 μg/rat) but not other doses of the antagonist (0.06, 0.125 and 0.25 μg/rat) increased both %OAT and %OAE, showing an anxiolytic-like effect for the higher dose of the drug. Similar administration route of sulpiride (0.25, 0.5, 0.75 and 1 μg/rat), a selective antagonist at dopamine D 2 receptor, had no significant effect on OAT%, OAE% and locomotor activity. Moreover, intra-CeA injection of nicotine (1 μg) with intra-NAc injection of sub-threshold doses of antagonists increased %OAT and %OAE without significant effect on locomotor activity. These findings may suggest the involvement of dopamine transmission, through D 1 and D 2 receptors of NAc shell, in the anxiogenic-like effect of nicotine in the EPM task. © 2012 Elsevier B.V. All rights reserved. Keywords: Nicotine SCH23390 Sulpiride Elevated plus maze 1. Introduction There are several investigations about negative health effects and economic consequences of tobacco use and nicotine dependency (Ho and Tyndale, 2007). The majority of smoking cessation attempts are unsuccessful (Cahill et al., 2007; McIlvain et al., 1995). Moreover, smoking cessation drugs, like bupropion and varenicline produce restricted therapeutic effects (Cahill et al., 2007; Hughes et al., 2007). Considering low rate effect of drug therapy for quitting smoking, there should be more research into the neurobiology of tobacco dependence. Both central amygdala (CeA) and the BRAIN RESEARCH 1460 (2012) 25 – 32 ⁎ Corresponding author at: Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Ghods Street, Italia St./1417755469, Tehran, Iran. Fax: +98 21 88991117. E-mail address: zarinmr@ams.ac.ir (M.R. Zarrindast). 0006-8993/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2012.04.036 Available online at www.sciencedirect.com www.elsevier.com/locate/brainres