Mansbach R S, Geyer M A, Braff D L
Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093.
Psychopharmacology (Berl). 1988;94(4):507-14. doi: 10.1007/BF00212846.
Prepulse inhibition is a cross-species phenomenon in which reflex responses to discrete sensory events are modified by weak prestimulation. In experiments designed to investigate the neuropharmacological mechanism of this form of information processing, and its relevance to schizophrenic psychopathology, apomorphine (0.125-4.0 mg/kg) and d-amphetamine (0.5-4.0 mg/kg) were administered to rats in an attempt to modify prepulse inhibition of the acoustic startle response. Rats were presented with 40 ms, 118 dB[A] acoustic pulses which were intermittently preceded by a weak 80 dB[A] acoustic prepulse. Both apomorphine and d-amphetamine induced a significant loss of prepulse inhibition, as reflected by increased pulse-preceded-by-prepulse versus pulse-alone startle magnitudes. Haloperidol (0.1 mg/kg), a specific D2 dopamine receptor antagonist, prevented the effects of 2.0 mg/kg apomorphine on prepulse inhibition, while having little effect by itself. An additional study investigated the effects of chronic intermittent administration of 2.5 mg/kg d-amphetamine. Rats given amphetamine for 8 consecutive days also displayed a loss of prepulse inhibition, with no evidence of tolerance. Finally, prepulse inhibition was examined under high- and low-intensity startle stimulus conditions; apomorphine (1.0 mg/kg) induced a loss of prepulse inhibition under both intensity conditions in approximately equal proportion. The results of these studies suggest a connection between sensorimotor gating, as measured by prepulse inhibition, and dopaminergic overactivity, supporting suggestions that information processing deficits in schizophrenia may be responsible for some psychotic symptoms and their effective treatment by antipsychotic D2 dopamine antagonists.
前脉冲抑制是一种跨物种现象，其中对离散感觉事件的反射反应会因弱的预刺激而改变。在旨在研究这种信息处理形式的神经药理学机制及其与精神分裂症精神病理学相关性的实验中，给大鼠注射阿扑吗啡（0.125 - 4.0毫克/千克）和右旋苯丙胺（0.5 - 4.0毫克/千克），试图改变听觉惊吓反应的前脉冲抑制。给大鼠呈现40毫秒、118分贝[A]的声脉冲，这些声脉冲之前会间歇性地出现一个80分贝[A]的弱声前脉冲。阿扑吗啡和右旋苯丙胺均导致前脉冲抑制显著丧失，这表现为前脉冲后接脉冲与单独脉冲的惊吓幅度增加。氟哌啶醇（0.1毫克/千克），一种特异性D2多巴胺受体拮抗剂，可预防2.0毫克/千克阿扑吗啡对前脉冲抑制的影响，而其自身影响很小。另一项研究调查了连续8天间歇性给予2.5毫克/千克右旋苯丙胺的效果。连续8天给予苯丙胺的大鼠也表现出前脉冲抑制丧失，且无耐受性证据。最后，在高强度和低强度惊吓刺激条件下检查前脉冲抑制；阿扑吗啡（1.0毫克/千克）在两种强度条件下均以大致相同的比例导致前脉冲抑制丧失。这些研究结果表明，以前脉冲抑制衡量的感觉运动门控与多巴胺能活动过度之间存在联系，支持了精神分裂症中信息处理缺陷可能导致某些精神病症状以及抗精神病D2多巴胺拮抗剂对其有效治疗的观点。
