Marttila Kristiina, Raattamaa Helena, Ahtee Liisa
Division of Pharmacology and Toxicology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5), Helsinki FIN-00014, Finland.
Neuropharmacology. 2006 Jul;51(1):44-51. doi: 10.1016/j.neuropharm.2006.02.014. Epub 2006 Apr 24.
DeltaFosB, a member of Fos family of transcription factors, is implicated in behavioural responses and synaptic plasticity induced by abused drugs. We studied the expressions of FosB/DeltaFosB and c-Fos immunohistochemically in two dopaminergic brain areas, nucleus accumbens (NAcc) and caudate-putamen (CPu). In mice neither 2- nor 7-week oral nicotine treatment induced expression of long-lived DeltaFosB isoforms although during the treatment in the NAcc FosB/DeltaFosB expression was increased as was c-Fos in the CPu. In rats given nicotine subcutaneously once daily for 5days FosB/DeltaFosB expression was elevated in the NAcc still after 24-h withdrawal suggesting accumulation of DeltaFosB but in the CPu neither FosB/DeltaFosB nor c-Fos expression was altered. Thus, in rats repeated nicotine administration seems mainly affect the NAcc paralleling with the evidence that nicotine stimulates preferentially mesolimbic dopamine system. Also, repeated nicotine induced behavioural sensitization in rats agreeing with suggested role of DeltaFosB in the development of psychomotor sensitization. However, in mice given nicotine via drinking fluid although striatal fosB and c-fos were activated by nicotine even after 7-week treatment no evidence of accumulation of long-lived DeltaFosB was found suggesting perhaps a species difference or more likely a role for the manner of administration.
DeltaFosB是转录因子Fos家族的成员之一，与滥用药物诱导的行为反应和突触可塑性有关。我们采用免疫组织化学方法研究了伏隔核（NAcc）和尾状核-壳核（CPu）这两个多巴胺能脑区中FosB/DeltaFosB和c-Fos的表达情况。在小鼠中，为期2周和7周的口服尼古丁治疗均未诱导长寿命DeltaFosB亚型的表达，尽管在治疗期间，伏隔核中FosB/DeltaFosB的表达增加，同时尾状核-壳核中的c-Fos表达也增加。在大鼠中，每天皮下注射尼古丁一次，持续5天，在停药24小时后，伏隔核中FosB/DeltaFosB的表达仍然升高，提示DeltaFosB的积累，但尾状核-壳核中FosB/DeltaFosB和c-Fos的表达均未改变。因此，在大鼠中，重复给予尼古丁似乎主要影响伏隔核，这与尼古丁优先刺激中脑边缘多巴胺系统的证据一致。此外，重复给予尼古丁可诱导大鼠行为敏感化，这与DeltaFosB在精神运动敏感化发展中的作用相符。然而，在通过饮水给予尼古丁的小鼠中，尽管纹状体中的fosB和c-fos在7周治疗后仍被尼古丁激活，但未发现长寿命DeltaFosB积累的证据，这可能提示存在种属差异，或者更可能与给药方式有关。
