Strain and sex matters: Differences in nicotine self-administration between outbred and recombinase-driver transgenic rat lines.
Strain and sex matters: Differences in nicotine self-administration between outbred and recombinase-driver transgenic rat lines.
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DOI：
10.1037/pha0000376
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发表时间：
2021-08
影响因子：
2.3
通讯作者：
Gipson CD
中科院分区：
文献类型：
--
作者：
Leyrer-Jackson JM;Overby PF;Bull A;Marusich JA;Gipson CD
尼古丁自我给药的临床前研究为该领域提供了重要价值，因为它们高度严格、受控、可以快速进行并且可推广到人类。考虑到尼古丁自我给药模型的转化价值，以及美国国立卫生研究院将性别作为生物学变量纳入的相对较新的指南，在两种远交大鼠品系中检查了尼古丁获取的品系和性别差异。对每种性别的Sprague-Dawley（SD）和Long Evans（LE;野生型和ChAT：：cre转基因）大鼠植入静脉内留置颈静脉导管。训练大鼠自我给予尼古丁（0.02 mg/kg/输注，伴随偶发性光+音调刺激）。采集标准设定为最低活动/非活动应答比为2：1，每次至少输注10次，必须在至少10次治疗中满足这两项要求。在10个阶段中，雄性SD大鼠自我给予的尼古丁显著多于雌性SD大鼠（p<0.05），表明该品系存在性别差异。LE雌性比SD雌性自我给予更多的尼古丁，表明雌性之间存在品系差异（p<0.05）。与LE男性和SD女性相比，SD男性在整个疗程中增加了尼古丁输注（p<0.05）。在达到标准的会话次数方面未观察到菌株或性别差异。未观察到野生型和转基因LE大鼠之间的差异。这些结果证明了SD和LE大鼠之间尼古丁自我给药的性别和品系差异，并可能有助于了解其他尼古丁自我给药模型的开发，其中性别和品系可能影响获取。
Preclinical studies of nicotine self-administration provide important value for the field as they are highly rigorous, controlled, can be conducted quickly, and are generalizable to humans. Given the translational value of the nicotine self-administration model, and the relatively new guildelines of the National Institutes of Health to include sex as a biological variable, strain and sex differences in nicotine acquisition were examined here in two outbred rat strains. Sprague-Dawley (SD) and Long Evans (LE; wild-type and ChAT::cre transgenic) rats of each sex were implanted with indwelling intravenous jugular catheters. Rats were trained to self-administer nicotine (0.02 mg/kg/infusion, paired with contingent light+tone stimuli). Acquisition criteria were set at a minimum active/inactive response ratio of 2:1 and a minimum of 10 infusions per session, both of which had to be met for a minimum of 10 sessions. Across 10 sessions, male SD rats self-administered significantly more nicotine than female SD rats (p<0.05), indicating a sex difference in this strain. LE females self-administered more nicotine than SD females indicative of a strain difference between females (p<0.05). SD males increased nicotine infusions across sessions compared to LE males and SD females (p<0.05). No strain or sex differences were observed in the number of sessions to reach criteria. No differences between wild-type and transgenic LE rats were observed. These results demonstrate sex and strain differences in nicotine self-administration between SD and LE rats and may lend insight into development of other nicotine self-administration models, where sex and strain may impact acquisition.
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