Gomez Adrian M, Sun Wei-Lun, Midde Narasimha M, Harrod Steven B, Zhu Jun
Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, Columbia, SC, 29208, USA.
Eur J Neurosci. 2015 Jan;41(1):109-19. doi: 10.1111/ejn.12758. Epub 2014 Oct 18.
Rats raised in an enriched condition (EC) exhibit alterations in the neurobiological and behavioral response to nicotine compared with rats reared in an impoverished condition (IC) or a standard condition (SC). The current study determined whether environmental enrichment differentially regulates extracellular signal-regulated kinase1/2 (ERK1/2) activity in the prefrontal cortex in rats following nicotine sensitization or nicotine self-administration. Under the saline control condition, EC rats displayed diminished baseline activity and greater sensitization to repeated administration of nicotine compared with IC and SC rats. After repeated saline injections, the basal levels of phosphorylated ERK1/2 (pERK1/2) were higher in EC compared with IC and SC rats, which was negatively correlated with their respective baseline activities. Repeated nicotine (0.35 mg/kg) injections induced pERK1/2 to similar levels in SC and IC rats; however, the induction of pERK1/2 in EC rats by nicotine was not significantly different from saline controls, owing to their high baseline. In the self-administration paradigm, EC rats self-administered less nicotine (0.03 mg/kg/infusion) relative to IC or SC rats on a fixed ratio-1 schedule of reinforcement. Accordingly, no differences in pERK1/2 were found between EC and IC rats self-administering saline, whereas nicotine self-administration resulted in an increase in pERK1/2 in IC rats but not in EC rats. Furthermore, the levels of pERK1/2 in EC and IC rats were positively correlated with their respective total number of nicotine infusions. Thus, these findings suggest that environmental enrichment alters the basal and nicotine-mediated pERK1/2, which may contribute to enrichment-induced behavioral alterations in response to nicotine.
与饲养在贫瘠环境（IC）或标准环境（SC）中的大鼠相比，饲养在丰富环境（EC）中的大鼠对尼古丁的神经生物学和行为反应会出现改变。本研究确定环境丰富化是否会在尼古丁致敏或尼古丁自我给药后，对大鼠前额叶皮质中的细胞外信号调节激酶1/2（ERK1/2）活性产生不同的调节作用。在生理盐水对照条件下，与IC和SC大鼠相比，EC大鼠的基线活性降低，对重复给予尼古丁的敏感性更高。在重复注射生理盐水后，与IC和SC大鼠相比，EC大鼠中磷酸化ERK1/2（pERK1/2）的基础水平更高，这与其各自的基线活性呈负相关。重复注射尼古丁（0.35mg/kg）使SC和IC大鼠中的pERK1/2诱导至相似水平；然而，由于EC大鼠的基线较高，尼古丁对其pERK1/2的诱导与生理盐水对照无显著差异。在自我给药范式中，在固定比率-1强化方案下，相对于IC或SC大鼠，EC大鼠自我给药的尼古丁（0.03mg/kg/注射）较少。因此，在自我注射生理盐水的EC和IC大鼠之间未发现pERK1/2有差异，而尼古丁自我给药导致IC大鼠中pERK1/2增加，但EC大鼠中未增加。此外，EC和IC大鼠中pERK1/2的水平与其各自的尼古丁注射总数呈正相关。因此，这些发现表明环境丰富化会改变基础和尼古丁介导的pERK1/2，这可能导致对尼古丁反应中丰富化诱导的行为改变。
