School of Psychology, Victoria University of Wellington, Wellington, New Zealand.
Addict Biol. 2018 Mar;23(2):620-630. doi: 10.1111/adb.12517. Epub 2017 May 12.
High comorbidity between schizophrenia and tobacco addiction has been well established. Explanatory theories include nicotine as a cognitive enhancer ameliorating symptoms of schizophrenia and underlying shared substrates increasing susceptibility to addiction in these individuals. To test these non-mutually exclusive theories, the maternal immune activation (MIA) model was utilized. To this end, pregnant Sprague Dawley rats were subcutaneously injected with a bacterial endotoxin, lipopolysaccharide (0.5 mg/kg), on gestation days 10 and 11. Selective attention and working memory in adult male offspring were subsequently assessed using the latent inhibition and delayed non-matching to sample paradigms both before and after nicotine or saline self-administration. MIA led to deficits in both latent inhibition and delayed non-matching to sample in male offspring. Further, these animals showed a small but significantly increased responding for nicotine during self-administration acquisition, although there was no difference in dose-response effect or in progressive ratio testing. However, nicotine, but not saline self-administration, significantly ameliorated the cognitive deficits induced by MIA. While the male offspring of mothers prenatally exposed to lipopolysaccharide was only slightly more sensitive to the reinforcing effects of nicotine, after self-administration, the MIA-induced cognitive deficits significantly improved. These data lend support for the self-medication hypothesis of schizophrenia.
精神分裂症和烟草成瘾之间存在高共病性已得到充分证实。解释理论包括尼古丁作为一种认知增强剂，可改善精神分裂症的症状，以及潜在的共同基础，使这些个体更容易成瘾。为了验证这些非互斥理论，利用了母体免疫激活（MIA）模型。为此，在妊娠第 10 和 11 天，向怀孕的 Sprague Dawley 大鼠皮下注射细菌内毒素脂多糖（0.5 mg/kg）。在尼古丁或生理盐水自我给药前后，使用潜伏抑制和延迟非匹配样本范式评估成年雄性后代的选择性注意和工作记忆。MIA 导致雄性后代的潜伏抑制和延迟非匹配样本都出现缺陷。此外，这些动物在自我给药获得期间对尼古丁的反应略有增加，但在剂量反应效应或递增比率测试中没有差异。然而，尼古丁而非生理盐水自我给药显著改善了 MIA 诱导的认知缺陷。虽然母体在产前暴露于脂多糖的雄性后代对尼古丁的强化作用仅略为敏感，但在自我给药后，MIA 诱导的认知缺陷显著改善。这些数据支持精神分裂症的自我药物治疗假说。
