title: Effect of nitric oxide synthase inhibitor and NMDA receptor antagonist on the development of nicotine sensitization of nucleus accumbens dopamine release: an in vivo microdialysis study.
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 (15 mg/kg, i.p.), MK-801 (0.3mg/kg, i.p.), or saline 30 min before injection of nicotine (0.4 mg/kg, s.c., once daily) for seven consecutive days. Twenty-four hours after the last drug injection, animals were challenged with local perfusion of 5 mM nicotine into the shell of nucleus accumbens for 60 min 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+/-235% (mean+/-S.E.M.) of basal level versus 520+/-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+/-58% and 445+/-90% of basal level, respectively versus 969+/-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.
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Hong
authors.forename: In Soon
authors.initials: IS
authors.lastname: Jung
authors.forename: Seong Ae
authors.initials: SA
authors.lastname: Bang
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Kim
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004338:Drug Combinations; D019335:Nitroarginine; D009569:Nitric Oxide; D016291:Dizocilpine Maleate; D009538:Nicotine; D019001:Nitric Oxide Synthase; D004298:Dopamine