Pehrson Alan L, Philibin Scott D, Gross Daniel, Robinson Susan E, Vann Robert E, Rosecrans John A, James John R
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Pharmacol Biochem Behav. 2008 May;89(3):424-31. doi: 10.1016/j.pbb.2008.01.018. Epub 2008 Feb 2.
Previous research in this laboratory has shown that nicotine's effects on spontaneous activity are contingent on individual differences, attenuating activity in high active rats and increasing it in low active rats. This study was designed to further evaluate this phenomenon, and to compare it with nicotine's effects on nicotinic acetylcholine receptor (nAChR) expression in several brain regions. Male and female Sprague-Dawley rats selected for differences in baseline activity were administered nicotine twice daily for 14 days, and its effects on spontaneous activity were evaluated following 1, 13 and 27 doses. Furthermore, [(3)H] epibatidine binding and plasma cotinine levels were evaluated 24 h after the 28th dose. Contrary to previous findings, the effects of repeated nicotine on spontaneous activity were minimally contingent on baseline activity levels. Following an initial attenuation, males, but not females, exhibited sensitization to nicotine's effects on spontaneous activity. [(3)H] epibatidine was significantly increased in several brain regions in both male and female nicotine-treated animals, and in females selected for high activity at baseline. However, a clear relationship between these effects and spontaneous activity was not found, due to the lack of consistent effects of nicotine administration and baseline activity on spontaneous activity. Interestingly, significant correlations suggest that rats exhibiting higher spontaneous activity on the final test day were differentially marked by higher [(3)H] epibatidine. Cotinine levels were higher in low activity males than in high activity males, but no differences were observed between high and low activity females. Thus, no clear relationship between this variable and spontaneous activity could be discerned. Based on these data, no simple relationships between the effects of nicotine administration or baseline activity on [(3)H] epibatidine binding, nicotine metabolism, or spontaneous activity were observed. However, a relationship between [(3)H] epibatidine and spontaneous activity on the final test day is suggested.
本实验室之前的研究表明，尼古丁对自发活动的影响取决于个体差异，它会减弱高活性大鼠的活动，而增强低活性大鼠的活动。本研究旨在进一步评估这一现象，并将其与尼古丁对多个脑区烟碱型乙酰胆碱受体（nAChR）表达的影响进行比较。选择基线活动存在差异的雄性和雌性Sprague-Dawley大鼠，每天给予尼古丁两次，持续14天，并在给予1、13和27次剂量后评估其对自发活动的影响。此外，在第28次给药后24小时评估[³H]依博加因结合情况和血浆可替宁水平。与之前的研究结果相反，重复给予尼古丁对自发活动的影响在很大程度上不取决于基线活动水平。在最初的活动减弱之后，雄性大鼠（而非雌性大鼠）对尼古丁对自发活动的影响出现了敏化。在接受尼古丁治疗的雄性和雌性动物以及基线时选择的高活性雌性动物的多个脑区中，[³H]依博加因显著增加。然而，由于给予尼古丁和基线活动对自发活动缺乏一致的影响，未发现这些影响与自发活动之间存在明确的关系。有趣的是，显著的相关性表明，在最终测试日表现出较高自发活动的大鼠，其[³H]依博加因水平也较高。低活性雄性大鼠的可替宁水平高于高活性雄性大鼠，但高活性和低活性雌性大鼠之间未观察到差异。因此，无法看出该变量与自发活动之间存在明确的关系。基于这些数据，未观察到给予尼古丁或基线活动对[³H]依博加因结合、尼古丁代谢或自发活动的影响之间存在简单的关系。然而，提示了[³H]依博加因与最终测试日的自发活动之间存在关系。
