Steiner Heinz, Warren Brandon L, Van Waes Vincent, Bolaños-Guzmán Carlos A
Department of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, FL, USA.
Prog Brain Res. 2014;211:13-30. doi: 10.1016/B978-0-444-63425-2.00002-7.
Psychostimulants such as methylphenidate (MPH) and antidepressants such as fluoxetine (FLX) are widely used in the treatment of various mental disorders or as cognitive enhancers. These medications are often combined, for example, to treat comorbid disorders. There is a considerable body of evidence from animal models indicating that individually these psychotropic medications can have detrimental effects on the brain and behavior, especially when given during sensitive periods of brain development. However, almost no studies investigate possible interactions between these drugs. This is surprising given that their combined neurochemical effects (enhanced dopamine and serotonin neurotransmission) mimic some effects of illicit drugs such as cocaine and amphetamine. Here, we summarize recent studies in juvenile rats on the molecular effects in the mid- and forebrain and associated behavioral changes, after such combination treatments. Our findings indicate that these combined MPH+FLX treatments can produce similar molecular changes as seen after cocaine exposure while inducing behavioral changes indicative of dysregulated mood and motivation, effects that often endure into adulthood.
哌甲酯（MPH）等精神兴奋药和氟西汀（FLX）等抗抑郁药被广泛用于治疗各种精神障碍或作为认知增强剂。这些药物经常联合使用，例如用于治疗共病障碍。动物模型中有大量证据表明，这些精神药物单独使用时会对大脑和行为产生有害影响，尤其是在大脑发育的敏感期使用时。然而，几乎没有研究调查这些药物之间可能的相互作用。鉴于它们联合产生的神经化学效应（增强多巴胺和5-羟色胺神经传递）类似于可卡因和苯丙胺等非法药物的一些效应，这一点令人惊讶。在此，我们总结了近期对幼年大鼠进行的研究，这些研究涉及联合治疗后中脑和前脑的分子效应以及相关行为变化。我们的研究结果表明，这些MPH+FLX联合治疗可产生与可卡因暴露后相似的分子变化，同时诱发表明情绪和动机失调的行为变化，这些影响往往会持续到成年期。
