Cummins Elizabeth D, Leedy Kristen K, Dose John M, Peterson Daniel J, Kirby Seth L, Hernandez Liza J, Brown Russell W
1 Department of Psychology, East Tennessee State University, Johnson City, TN, USA.
3 Department of Psychology, St Norbert College, De Pere, WI, USA.
J Psychopharmacol. 2017 Jan;31(1):75-85. doi: 10.1177/0269881116681458. Epub 2016 Dec 9.
This study analyzed the interaction of adolescent methylphenidate on the behavioral response to nicotine and the effects of these drug treatments on brain-derived neurotrophic factor in the nucleus accumbens and hippocampus in male and female Sprague-Dawley rats. Animals were intraperitoneal administered 1 mg/kg methylphenidate or saline using a "school day" regimen (five days on, two days off) beginning on postnatal day (P)28 and throughout behavioral testing. In Experiment 1, animals were intraperitoneal administered 0.5 mg/kg (free base) nicotine or saline every second day for 10 days from P45-P63 and tested after a three-day drug washout on the forced swim stress task on P67-P68. Results revealed that adolescent methylphenidate blunted nicotine behavioral sensitization. However, methylphenidate-treated rats given saline during sensitization demonstrated decreased latency to immobility and increased immobility time on the forced swim stress task in males that was reduced by nicotine. In Experiment 2, a different set of animals were conditioned to nicotine (0.6 mg/kg free base) or saline using the conditioned place preference behavioral paradigm from P44-P51, and given a preference test on P52. On P53, the nucleus accumbens and hippocampus were analyzed for brain-derived neurotrophic factor. Methylphenidate enhanced nicotine-conditioned place preference in females and nicotine produced conditioned place preference in males and females pre-exposed to saline in adolescence. In addition, methylphenidate and nicotine increased nucleus accumbens brain-derived neurotrophic factor in females and methylphenidate enhanced hippocampus brain-derived neurotrophic factor in males and females. Methylphenidate adolescent exposure using a clinically relevant dose and regimen results in changes in the behavioral and brain-derived neurotrophic factor responses to nicotine in adolescence that are sex-dependent.
本研究分析了青少年使用哌甲酯对尼古丁行为反应的影响，以及这些药物治疗对雄性和雌性斯普拉格-道利大鼠伏隔核和海马中脑源性神经营养因子的作用。从出生后第（P）28天开始，采用“上学日”方案（给药5天，停药2天）对动物腹腔注射1mg/kg哌甲酯或生理盐水，并持续整个行为测试阶段。在实验1中，从P45 - P63每隔一天给动物腹腔注射0.5mg/kg（游离碱）尼古丁或生理盐水，持续10天，并在P67 - P68进行为期三天的药物洗脱后，对强迫游泳应激任务进行测试。结果显示，青少年使用哌甲酯会减弱尼古丁行为敏化。然而，在敏化期间给予生理盐水的哌甲酯处理大鼠，在强迫游泳应激任务中，雄性大鼠的不动潜伏期缩短，不动时间增加，而尼古丁可减轻这种情况。在实验2中，另一组动物在P44 - P51期间使用条件性位置偏爱行为范式对尼古丁（0.6mg/kg游离碱）或生理盐水进行条件化处理，并在P52进行偏爱测试。在P53，对伏隔核和海马进行脑源性神经营养因子分析。哌甲酯增强了雌性大鼠对尼古丁的条件性位置偏爱，尼古丁在青春期预先接触生理盐水的雄性和雌性大鼠中产生了条件性位置偏爱。此外，哌甲酯和尼古丁增加了雌性大鼠伏隔核中的脑源性神经营养因子，哌甲酯增强了雄性和雌性大鼠海马中的脑源性神经营养因子。青少年使用临床相关剂量和方案的哌甲酯会导致青春期对尼古丁的行为和脑源性神经营养因子反应发生性别依赖性变化。
