title: Nicotine tolerance to PC12 cell line: acute and chronic exposures modulate dopamine D2 receptor and tyrosine hydroxylase expression.
abstract: PC12 is a clonal cell line from chromaffin tumor of rat adrenal pheochromocytoma that releases catecholamine including dopamine, which via interaction with its receptor (D(1) and D(2) receptor), is known to be involved in reward and reinforcement properties of many addictive drugs like nicotine. Nicotine tolerance is the key aspect of nicotine addiction. However, nicotine tolerance on dopamine receptors in PC12 cell line is poorly understood. In this paper, we have demonstrated the tolerance to acute and chronic nicotine administrations on PC12 cell line on the basis of the expressions of dopamine receptors and tyrosine hydroxylase, the rate-limiting enzyme of dopamine biosynthesis, by Western blot, immunohistochemistry and in situ hybridization. In vitro treatment of nicotine resulted in similar expressional changes of dopamine D(2) receptor and tyrosine hydroxylase at protein and mRNA levels in dose- and time-dependent manner, whereas dopamine D(1) receptor did not reveal any positive output. Moreover, moderate to strong signals were obtained from 0.1 to 10 microM of nicotine concentrations and the signals were gradually decreased at 100 and 1000 microM nicotine concentrations relative to the untreated control cell line. Therefore, this study implied a new approach towards nicotine tolerance which is likely to be related to the modulation of dopamine D(2) receptor and tyrosine hydroxylase expressions by chronic and acute nicotine exposures in PC12 cell line.
authors.affiliation: Division of Life Science, Applied Life Science (Brain Korea 21 and EB-NCRC), Gyeongsang National University, Jinju 660-701, South Korea.
authors.forename: Nibedita
authors.initials: N
authors.lastname: Naha
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Jin Su
authors.initials: JS
authors.lastname: Hwang
authors.forename: Jong Yoon
authors.initials: JY
authors.lastname: Bahk
authors.forename: Moon Seok
authors.initials: MS
authors.lastname: Park
authors.forename: Sang Yeol
authors.initials: SY
authors.lastname: Lee
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Myeong Ok
authors.initials: MO
authors.lastname: Kim
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D015870:Gene Expression / Q000187:drug effects; D009538:Nicotine / Q000008:administration & dosage*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D009538:Nicotine; D014446:Tyrosine 3-Monooxygenase