Russig Holger, Murphy Carol A, Feldon Joram
Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology (ETH Zurich), Postfach Schorenstrasse 16, 8603 Schwerzenbach, Switzerland.
Psychopharmacology (Berl). 2003 Sep;169(3-4):340-53. doi: 10.1007/s00213-002-1254-4. Epub 2002 Nov 12.
Psychomotor stimulants can induce psychotic states in humans that closely resemble those observed in patients with idiopathic schizophrenia. Attentional and sensorimotor gating impairments are observed in schizophrenic patients using the latent inhibition (LI) and prepulse inhibition (PPI) behavioral assays, respectively. Our previous studies demonstrated that after 4 days of withdrawal from a period of amphetamine (AMPH) administration, animals exhibited disrupted LI but normal PPI.
The aim of the present study was to test PPI in AMPH-withdrawn rats under experimental conditions similar to those used to best demonstrate locomotor sensitization following AMPH withdrawal.
We examined the effects on PPI of (1) pairing drug injections with PPI test-associated cues, (2) administration of a low-dose dopamine agonist challenge and (3) testing following longer withdrawal periods (23, 30, 60 days).
Although none of these conditions revealed a disruption of PPI in AMPH-withdrawn rats, we did observe that the acoustic startle response was reduced during a restricted time period following AMPH withdrawal. Similar to our previous findings, AMPH-withdrawn animals showed disrupted LI on day 16 of withdrawal and locomotor sensitization to a challenge injection of AMPH after 62 days of withdrawal.
We conclude that the effects of repeated AMPH on PPI are not modulated by the same experimental parameters known to be important for eliciting locomotor sensitization and that withdrawal from the schedule of AMPH administration used in this study models only specific cognitive dysfunctions linked to schizophrenic symptoms, since LI was disrupted but PPI was not affected.
精神运动兴奋剂可在人类中诱发与特发性精神分裂症患者所观察到的极为相似的精神病状态。分别使用潜伏抑制（LI）和前脉冲抑制（PPI）行为测定法，在精神分裂症患者中观察到了注意力和感觉运动门控障碍。我们之前的研究表明，在停用苯丙胺（AMPH）一段时间4天后，动物表现出LI受损但PPI正常。
本研究的目的是在与用于最佳证明AMPH戒断后运动敏化的实验条件相似的情况下，测试AMPH戒断大鼠的PPI。
我们研究了以下因素对PPI的影响：（1）将药物注射与PPI测试相关线索配对；（2）给予低剂量多巴胺激动剂激发；（3）在更长的戒断期（23、30、60天）后进行测试。
尽管这些条件均未显示AMPH戒断大鼠的PPI受损，但我们确实观察到在AMPH戒断后的一段受限时间内，听觉惊吓反应有所降低。与我们之前的发现相似，AMPH戒断动物在戒断第16天表现出LI受损，并且在戒断62天后对一次性注射AMPH表现出运动敏化。
我们得出结论，重复给予AMPH对PPI的影响不受已知对引发运动敏化很重要的相同实验参数的调节，并且本研究中使用的AMPH给药方案的戒断仅模拟了与精神分裂症症状相关的特定认知功能障碍，因为LI受损但PPI未受影响。
