부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.neulet.2006.09.052 Byline: Soo Kyung Hong (a)(b), In Soon Jung (a), Seong Ae Bang (a), Sang Eun Kim (a)(b) Keywords: Nitric oxide (NO); NMDA receptor; Nicotine sensitization; Dopamine release; Nucleus accumbens Abstract: We have previously found that the neuronal nitric oxide synthase inhibitor N-nitro-l-arginine (l-NNA) and the noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 prevent behavioral sensitization to nicotine. This study aimed to investigate the effect of l-NNA and MK-801 on a neurochemical component of nicotine sensitization by evaluating the effect of the drugs on nicotine sensitization of nucleus accumbens dopamine (DA) release. Sprague-Dawley rats were pretreated with l-NNA (15mg/kg, i.p.), MK-801 (0.3mg/kg, i.p.), or saline 30min before injection of nicotine (0.4mg/kg, s.c., once daily) for seven consecutive days. Twenty-four hours after the last drug injection, animals were challenged with local perfusion of 5mM nicotine into the shell of nucleus accumbens for 60min and DA release was monitored using in vivo microdialysis. In rats treated with repeated nicotine, acute nicotine challenge induced a greater increase of accumbal DA release than in saline-treated animals (maximal DA response=969[+ or -]235% (mean[+ or -]S.E.M.) of basal level versus 520[+ or -]93%, p =0.042). Co-administration of l-NNA or MK-801 with nicotine attenuated an increase of DA release elicited by acute nicotine challenge, compared with nicotine alone (maximal DA response=293[+ or -]58% and 445[+ or -]90% of basal level, respectively versus 969[+ or -]235%, p =0.004 and p =0.013, respectively). These data demonstrate that l-NNA and MK-801 block the development of nicotine sensitization of nucleus accumbens DA release, further supporting the involvement of nitric oxide and NMDA receptors in the development of behavioral sensitization to nicotine. Author Affiliation: (a) Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea (b) Department of Neuroscience, Seoul National University College of Medicine, Seoul, South Korea Article History: Received 29 August 2006; Revised 21 September 2006; Accepted 21 September 2006