Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn St, HSFII, Room S251, Baltimore, MD 21201, USA.
Psychopharmacology (Berl). 2013 Mar;226(1):45-51. doi: 10.1007/s00213-012-2882-y. Epub 2012 Sep 26.
Patients with schizophrenia exhibit high comorbidity for substance abuse, but the biological underpinnings of this dual-diagnosis condition are still unclear. Previous studies have shown that rats with a neonatal ventral hippocampal lesion (NVHL), a widely used developmental animal model of schizophrenia, exhibit increased cocaine and methamphetamine self-administration and cocaine-induced reinstatement.
Here, we assessed whether a NVHL would also potentiate cue-induced reinstatement of cocaine seeking and the time-dependent increases in cue-induced cocaine seeking after withdrawal (incubation of cocaine craving) in adult rats.
Rats were trained to self-administer cocaine (3 or 6 h/day with 0.75 mg kg(-1) infusion(-1) paired with a tone-light cue) for 10 days, followed by extinction training (3 h/day) and cue-induced reinstatement of cocaine seeking. Other rats were tested for incubation of cocaine craving, assessed in extinction tests 1 and 30 days after the last self-administration session.
Although there was no significant difference in cocaine intake between NVHL and sham controls, NVHL rats took significantly longer to reach an a priori set extinction criterion and exhibited enhanced cue-induced reinstatement. However, while cue-induced cocaine seeking was higher after 30 days than after 1 day of withdrawal (incubation of cocaine craving), the NVHL had no effect on this incubation.
These data confirm previous reports on enhanced resistance to extinction after NVHL and demonstrate that NVHL rats exhibit enhanced cue-induced reinstatement of cocaine seeking after extinction, a measure of drug relapse.
精神分裂症患者存在物质滥用共病的高发病率，但这种双重诊断状况的生物学基础仍不清楚。先前的研究表明，新生大鼠腹侧海马损伤（NVHL），一种广泛使用的精神分裂症发育动物模型，表现出可卡因和甲基苯丙胺自我给药增加，以及可卡因诱导的复吸。
本研究旨在评估 NVHL 是否也会增强线索诱导的可卡因寻求的复吸，以及在成年大鼠戒断（可卡因渴求潜伏期）后线索诱导的可卡因寻求的时间依赖性增加（可卡因渴求潜伏期）。
大鼠接受可卡因自我给药训练（每天 3 或 6 小时，剂量为 0.75mg/kg 输注量，与音光线索配对）10 天，随后进行消退训练（每天 3 小时）和线索诱导的可卡因寻求复吸。其他大鼠接受可卡因渴求潜伏期的测试，在最后一次自我给药后 1 天和 30 天的消退测试中进行评估。
虽然 NVHL 组和假手术对照组之间可卡因摄入量没有显著差异，但 NVHL 组大鼠达到预先设定的消退标准所需的时间更长，并且表现出增强的线索诱导的复吸。然而，尽管在戒断 30 天后，线索诱导的可卡因寻求比 1 天后更高（可卡因渴求潜伏期），但 NVHL 对这种潜伏期没有影响。
这些数据证实了先前关于 NVHL 后消退抵抗增强的报道，并表明 NVHL 大鼠在消退后表现出增强的线索诱导的可卡因寻求复吸，这是药物复发的一种衡量标准。
