Areal Lorena Bianchine, Herlinger Alice Laschuk, Pelição Fabrício Souza, Martins-Silva Cristina, Pires Rita Gomes Wanderley
Laboratory of Molecular and Behavioral Neurobiology, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, Brazil; Graduate Program in Neuroscience, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Laboratory of Molecular and Behavioral Neurobiology, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, Brazil; Department of Physiological Sciences, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, Brazil.
J Psychiatr Res. 2017 Aug;91:57-63. doi: 10.1016/j.jpsychires.2017.03.005. Epub 2017 Mar 6.
Crack cocaine (crack) addiction represents a major social and health burden, especially seeing as users are more prone to engage in criminal and violent acts. Crack users show a higher prevalence of psychiatric comorbidities - particularly antisocial personality disorders - when compared to powder cocaine users. They also develop cognitive deficits related mainly to executive functions, including working memory. It is noteworthy that stimulant drugs can induce psychotic states, which appear to mimic some symptoms of schizophrenia among users. Social withdraw and executive function deficits are, respectively, negative and cognitive symptoms of schizophrenia mediated by reduced dopamine (DA) tone in the prefrontal cortex (PFC) of patients. That could be explained by an increased expression of D2R short isoform (D2S) in the PFC of such patients and/or by hypofunctioning NMDA receptors in this region. Reduced DA tone has already been described in the PFC of mice exposed to crack smoke. Therefore, it is possible that behavioral alterations presented by crack users result from molecular and biochemical neuronal alterations akin to schizophrenia. Accordingly, we found that upon crack inhalation mice have shown decreased social interaction and working memory deficits analogous to schizophrenia's symptoms, along with increased D2S/D2L expression ratio and decreased expression of NR1, NR2A and NR2B NMDA receptor subunits in the PFC. Herein we propose two possible mechanisms to explain the reduced DA tone in the PFC elicited by crack consumption in mice, bringing also the first direct evidence that crack use may result in schizophrenia-like neurochemical, molecular and behavioral alterations.
快克可卡因成瘾是一项重大的社会和健康负担，尤其是考虑到使用者更倾向于实施犯罪和暴力行为。与吸食粉末可卡因的使用者相比，快克可卡因使用者出现精神疾病共病的比例更高，尤其是反社会人格障碍。他们还会出现主要与执行功能相关的认知缺陷，包括工作记忆。值得注意的是，兴奋剂药物可诱发精神病状态，这在使用者中似乎会模仿精神分裂症的一些症状。社交退缩和执行功能缺陷分别是精神分裂症的阴性和认知症状，由患者前额叶皮质（PFC）中多巴胺（DA）水平降低介导。这可以通过此类患者PFC中D2R短异构体（D2S）表达增加和/或该区域NMDA受体功能低下进行解释。在暴露于快克烟雾的小鼠的PFC中已经发现DA水平降低。因此，快克可卡因使用者出现的行为改变可能是由类似于精神分裂症的分子和生化神经元改变引起的。相应地，我们发现吸入快克可卡因后，小鼠表现出社交互动减少和类似于精神分裂症症状的工作记忆缺陷，同时PFC中D2S/D2L表达比率增加，NR1、NR2A和NR2B NMDA受体亚基的表达减少。在此，我们提出两种可能的机制来解释小鼠摄入快克可卡因后PFC中DA水平降低的现象，同时也首次提供了直接证据，表明使用快克可卡因可能导致类似精神分裂症的神经化学、分子和行为改变。
