Department of Psychology, St. Mary's College of Maryland, 18952 E. Fisher Rd., St. Mary's City, MD 20686-3001, USA.
Behav Brain Res. 2012 Jun 1;231(2):323-36. doi: 10.1016/j.bbr.2012.03.045. Epub 2012 Apr 6.
The widely accepted rat vacuous chewing movement model for tardive dyskinesia could be more fully mined through greater focus on individual variability in vulnerability to this neuroleptic-induced behavior. We have examined parallels between behavioral and neurobiological variability within a cohort in order to evaluate the role that neurobiological factors might play in determining susceptibility to tardive dyskinesia. Inter-observer reliability and individual consistency across time, in both spontaneous and neuroleptic-induced vacuous chewing movements, were empirically demonstrated. While this behavior increased across 8 months of observation in both vehicle controls and haloperidol-treated rats, pre-treatment baselines were predictive of final levels across individuals only in the vehicle control group, not the haloperidol-treated group. Haloperidol-induced elevations in neostriatal D2 and GAD(67) mRNA were not correlated with individual variability in haloperidol-induced vacuous chewing movements. Ambient noise during the observations was found to exacerbate chronic haloperidol-induced, but not spontaneous vacuous chewing movements. Significant correlations were found among the haloperidol-treated rats between nigral and tegmental GAD(67) and tegmental α7 mRNA levels, measured by in situ hybridization histochemistry, and vacuous chewing movements, specifically in the noisy conditions. Variability in these secondary responses to primary striatal dopamine and GABA perturbations may play a role in determining vulnerability to vacuous chewing movements, and by analogy, tardive dyskinesia. Both the differential predictive value of baseline vacuous chewing movements and the differential effect of noise, between controls and haloperidol-treated rats, add to evidence that haloperidol-induced vacuous chewing movements are regulated, in part, by different mechanisms than those mediating spontaneous vacuous chewing movements.
被广泛接受的大鼠空嚼运动模型可用于迟发性运动障碍，通过更加关注易患这种神经安定药诱导行为的个体差异，可以更充分地挖掘该模型。我们已经检查了一个队列中行为和神经生物学变异性之间的相似性，以评估神经生物学因素在决定迟发性运动障碍易感性方面可能发挥的作用。自发和神经安定药诱导的空嚼运动的观察者间可靠性和个体间时间一致性得到了实证证明。虽然这种行为在 8 个月的观察中在载体对照和氟哌啶醇处理的大鼠中均增加，但只有在载体对照组，而不是氟哌啶醇处理组中，预处理基线可以预测个体的最终水平。氟哌啶醇诱导的新纹状体 D2 和 GAD(67)mRNA 的升高与氟哌啶醇诱导的空嚼运动的个体变异性无关。研究发现，观察期间的环境噪声会加剧慢性氟哌啶醇诱导的空嚼运动，但不会加剧自发空嚼运动。通过原位杂交组织化学测量，氟哌啶醇处理的大鼠之间存在显著相关性，在嘈杂环境中，黑质和被盖部 GAD(67)和被盖部α7mRNA 水平与空嚼运动之间存在显著相关性。这些对初级纹状体多巴胺和 GABA 扰动的次要反应的变异性可能在决定空嚼运动易感性方面发挥作用，并且可以类推，在决定迟发性运动障碍易感性方面发挥作用。基线空嚼运动的差异预测价值和噪声对对照组和氟哌啶醇处理组大鼠的差异影响，增加了氟哌啶醇诱导的空嚼运动部分由调节自发空嚼运动的不同机制调节的证据。
