Bakshi V P, Swerdlow N R, Braff D L, Geyer M A
Department of Neurosciences, University of California at San Diego, La Jolla 92093-0804, USA.
Biol Psychiatry. 1998 Mar 15;43(6):436-45. doi: 10.1016/s0006-3223(97)00246-1.
Prepulse inhibition (PPI) of startle provides an operational measure of sensorimotor gating in which a weak stimulus presented prior to a startling stimulus reduces the startle response. PPI deficits observed in schizophrenia patients can be modeled in rats by individual housing from weaning until adulthood. Deficits in PPI produced by isolation rearing can be reversed by antipsychotics.
We evaluated the ability of Seroquel and olanzapine to reverse the isolation-induced disruption of PPI. Rats housed for 8 weeks singly or in groups of 3 were tested every 2 weeks after either Seroquel (0, 5.0 mg/kg) or olanzapine (0, 2.5, 5.0 mg/kg). Startle was elicited by 120-dB pulses presented either with or without prepulses (3, 6, or 12 dB above a 65-dB background).
Isolation rearing repeatedly disrupted PPI and sometimes increased startle reactivity. Seroquel reversed these deficits without affecting PPI in socially reared controls. Olanzapine (2.5 mg/kg) reversed the isolation rearing-induced PPI deficit and tended to increase basal PPI levels. Both antipsychotics antagonized the isolation rearing-induced increase in startle reactivity.
Isolation rearing produces deficits in sensorimotor gating in rats that are reversible by atypical antipsychotics, and may therefore aid in identifying new treatments for schizophrenia.
惊吓前脉冲抑制（PPI）为感觉运动门控提供了一种可操作的测量方法，即在惊吓刺激之前呈现的弱刺激会降低惊吓反应。精神分裂症患者中观察到的PPI缺陷可通过将大鼠从断奶期至成年期单独饲养来进行模拟。隔离饲养导致的PPI缺陷可被抗精神病药物逆转。
我们评估了喹硫平和奥氮平逆转隔离诱导的PPI破坏的能力。将单独饲养或3只一组饲养8周的大鼠，在给予喹硫平（0、5.0mg/kg）或奥氮平（0、2.5、5.0mg/kg）后，每2周进行一次测试。通过在有或无预脉冲（比65dB背景高3、6或12dB）的情况下呈现120dB脉冲来引发惊吓反应。
隔离饲养反复破坏PPI，有时还会增加惊吓反应性。喹硫平可逆转这些缺陷，且不影响群居饲养对照组的PPI。奥氮平（2.5mg/kg）可逆转隔离饲养诱导的PPI缺陷，并倾向于提高基础PPI水平。两种抗精神病药物均拮抗隔离饲养诱导的惊吓反应性增加。
隔离饲养会导致大鼠感觉运动门控缺陷，非典型抗精神病药物可使其逆转，因此可能有助于确定精神分裂症的新治疗方法。
