Kippin Tod E, Szumlinski Karen K, Kapasova Zuzana, Rezner Betsy, See Ronald E
Department of Psychology, The Neuroscience Research Institute, University of California, Santa Barbara, CA 93106-9660, USA.
Neuropsychopharmacology. 2008 Mar;33(4):769-82. doi: 10.1038/sj.npp.1301447. Epub 2007 May 9.
Early environmental events have profound influences on a wide range of adult behavior. In the current study, we assessed the influence of maternal stress during gestation on psychostimulant and neurochemical responsiveness to cocaine, cocaine self-administration, and reinstatement of cocaine-seeking in adult offspring. Pregnant, female Sprague-Dawley rats were subjected to either no treatment or to restraint stress three times per day for the last 7 days of gestation and cocaine-related behavior was assessed in offspring at 10 weeks of age. Relative to controls, a noncontingent cocaine injection elevated locomotor activity as well as nucleus accumbens levels of extracellular dopamine and glutamate to a greater extent in both cocaine-naive and cocaine-experienced prenatal stress (PNS) rats and elevated prefrontal cortex dopamine in cocaine-experienced PNS rats. To assess the impact of PNS on cocaine addiction-related behavior, rats were trained to lever press for intravenous (i.v.) infusions of cocaine (0.25, 0.5, or 1 mg/kg/infusion), with each infusion paired with a light+tone-conditioned stimulus. Lever-pressing was extinguished and cocaine-seeking reinstated by re-exposure to the conditioned cues or by intraperitoneal cocaine-priming injections (5 or 10 mg/kg). PNS elevated active lever responding both during extinction and cocaine-primed reinstatement, but not during self-administration or conditioned-cued reinstatement. PNS also did not alter intake during self-administration. These findings demonstrate that PNS produces enduring nervous system alterations that increase the psychomotor stimulant, motivational, and neurochemical responsiveness to noncontingent cocaine. Thus, early environmental factors contribute to an individual's initial responsiveness to cocaine and propensity to relapse to cocaine-seeking.
早期环境事件对成年后的广泛行为有着深远影响。在本研究中，我们评估了孕期母体应激对成年后代对精神兴奋剂的反应、对可卡因的神经化学反应、可卡因自我给药以及可卡因觅药行为恢复的影响。怀孕的雌性斯普拉格-道利大鼠在孕期的最后7天，要么不接受任何处理，要么每天接受3次束缚应激，在后代10周龄时评估与可卡因相关的行为。相对于对照组，非条件性可卡因注射在未接触过可卡因和有过可卡因接触经历的产前应激（PNS）大鼠中，均能更大程度地提高运动活性以及伏隔核细胞外多巴胺和谷氨酸水平，并且在有过可卡因接触经历的PNS大鼠中能提高前额叶皮质多巴胺水平。为了评估PNS对可卡因成瘾相关行为的影响，训练大鼠按压杠杆以静脉注射可卡因（0.25、0.5或1毫克/千克/次注射），每次注射伴有光+音调条件刺激。杠杆按压行为消退后，通过再次暴露于条件线索或腹腔注射可卡因激发注射（5或10毫克/千克）来恢复可卡因觅药行为。PNS在消退期和可卡因激发恢复期中均提高了主动杠杆反应，但在自我给药期或条件线索恢复期中没有提高。PNS也没有改变自我给药期间的摄入量。这些发现表明，PNS会产生持久的神经系统改变，增加对非条件性可卡因的精神运动兴奋剂、动机和神经化学反应。因此，早期环境因素有助于个体对可卡因的初始反应以及复发至可卡因觅药行为的倾向。
