Wetzell B Bradley, Muller Mirabella M, Flax Shaun M, King Heather E, DeCicco-Skinner Kathleen, Riley Anthony L
Psychopharmacology Laboratory, Department of Psychology, American University, Washington, DC, 20016, USA,
Psychopharmacology (Berl). 2015 Aug;232(15):2837-47. doi: 10.1007/s00213-015-3924-z. Epub 2015 Apr 17.
Exogenous brain-derived neurotrophic factor (BDNF) in the insular cortex (IC) is known to influence conditioned taste avoidance (CTA) learning, but little is known of its endogenous role in the phenomenon. Preexposure to many abusable compounds attenuates their ability to induce CTA, thus providing a possible platform from which to further elucidate the endogenous role of IC BDNF in CTA.
The role of IC BDNF in CTA learning was examined by assessing the effect of preexposure to methylphenidate (MPH) on MPH-induced CTA, followed by expression between preexposure groups of BDNF in the IC, central nucleus of the amygdala (CeA), and the nucleus accumbens (NAc).
Following preexposure to MPH (18 mg/kg), CTAs induced by MPH (0, 10, 18, and 32 mg/kg) were assessed in adult male Sprague-Dawley rats (n = 64). In separate groups (n = 31), differences in BDNF and tropomyosin-related kinase receptor-B (TrkB) were assessed using Western blots following similar preexposure and conditioning procedures.
Preexposure to MPH significantly blunted MPH-CTA compared to preexposure to vehicle. Unexpectedly, there were no significant effects of MPH on BDNF activity following CTA, but animals preexposed to MPH exhibited decreased activity in the CeA and enhanced activity in the IC and NAc.
Preexposure to MPH attenuates its aversive effects on subsequent presentations, and BDNF's impact on CTA learning may be dependent upon its temporal relation to other CTA-related intracellular cascades.
已知岛叶皮质(IC)中的外源性脑源性神经营养因子(BDNF)会影响条件性味觉厌恶(CTA)学习,但对其在该现象中的内源性作用知之甚少。预先接触许多可滥用化合物会减弱它们诱导CTA的能力,从而提供了一个可能的平台,以便进一步阐明IC BDNF在CTA中的内源性作用。
通过评估预先接触哌醋甲酯(MPH)对MPH诱导的CTA的影响,随后检测预先接触组之间IC、杏仁核中央核(CeA)和伏隔核(NAc)中BDNF的表达,来研究IC BDNF在CTA学习中的作用。
在成年雄性Sprague-Dawley大鼠(n = 64)中,预先接触MPH(18 mg/kg)后,评估由MPH(0、10、18和32 mg/kg)诱导的CTA。在单独的组(n = 31)中,采用类似的预先接触和条件作用程序后,使用蛋白质免疫印迹法评估BDNF和原肌球蛋白相关激酶受体B(TrkB)的差异。
与预先接触溶剂相比,预先接触MPH显著减弱了MPH-CTA。出乎意料的是,CTA后MPH对BDNF活性没有显著影响,但预先接触MPH的动物在CeA中的活性降低,而在IC和NAc中的活性增强。
预先接触MPH会减弱其对后续呈现的厌恶作用,并且BDNF对CTA学习的影响可能取决于其与其他CTA相关细胞内级联反应的时间关系。