Murphy C A, Di Iorio L, Feldon J
Laboratory of Behavioral Neurobiology, Swiss Federal Institute of Technology (ETH-Zurich), Schwerzenbach.
Psychopharmacology (Berl). 2001 Jul;156(2-3):155-64. doi: 10.1007/s002130100759.
Chronic intermittent administration of amphetamine and cocaine can precipitate psychotic episodes in humans and produce persistent behavioral changes (i.e. increased locomotion, stereotypy) in the rat. The psychostimulant sensitization model of psychosis holds that the repeated administration of drugs such as amphetamine and cocaine induces long-lasting neuroadaptations and behavioral outcomes in animals that parallel aspects of the schizophrenic condition.
In the present study, we attempted to validate this model further by examining the effects of short-term withdrawal from repeated administration of cocaine and amphetamine on performance in two animal behavioral models of cognitive deficits found in schizophrenia: latent inhibition and prepulse inhibition. Reductions in both of these behavioral phenomena have been reported in schizophrenic patients and in acutely amphetamine-treated rats.
Animals were tested after 4 days of withdrawal from 5 days of daily systemic 20 mg/kg cocaine or 1.5 mg/kg amphetamine injections for either latent inhibition of two-way active avoidance acquisition or prepulse inhibition of an acoustic startle response.
Our results indicate that, rather than reducing the expression of these behaviors, withdrawal from either cocaine or amphetamine enhanced the expression of latent inhibition of the active avoidance response while having no effect on prepulse inhibition of acoustic startle.
These data indicate that although the sensitized response to amphetamine and cocaine administration may model some aspects of schizophrenic psychosis, behaviors exhibited by sensitized animals in the absence of an acute drug challenge are not consistent with models of the positive symptoms of schizophrenia.
长期间歇性给予苯丙胺和可卡因可诱发人类精神病发作，并在大鼠中产生持续的行为变化（如活动增加、刻板行为）。精神病的精神兴奋剂敏感化模型认为，反复给予苯丙胺和可卡因等药物会在动物体内诱导出持久的神经适应性变化和行为结果，这些变化与精神分裂症的某些方面相似。
在本研究中，我们试图通过研究短期停用反复给予的可卡因和苯丙胺对精神分裂症中发现的两种认知缺陷动物行为模型（潜伏抑制和前脉冲抑制）表现的影响，进一步验证该模型。精神分裂症患者和急性给予苯丙胺治疗的大鼠中均有这两种行为现象的减少的报道。
动物在每天全身注射20mg/kg可卡因或1.5mg/kg苯丙胺5天后停药4天，然后进行双向主动回避习得的潜伏抑制或听觉惊吓反应的前脉冲抑制测试。
我们的结果表明，停用可卡因或苯丙胺并没有减少这些行为的表现，反而增强了主动回避反应的潜伏抑制表现，而对听觉惊吓的前脉冲抑制没有影响。
这些数据表明，虽然对苯丙胺和可卡因给药的敏感化反应可能模拟了精神分裂症精神病的某些方面，但在没有急性药物刺激的情况下，敏感化动物表现出的行为与精神分裂症阳性症状模型不一致。
