Neuroscience and Behavioral Pharmacology Laboratory, Department of Psychiatry, McLean Hospital/Harvard Medical School, Belmont, MA, USA.
Laboratory of Neuropsychiatry, Psychiatric Centre Copenhagen, Mental Health Services in the Capital Region of Denmark, Forskningsenheder, Hovedvejen 17, 1. sal, 2000 Frederiksberg, Copenhagen, Denmark.
Psychopharmacology (Berl). 2023 Sep;240(9):2005-2012. doi: 10.1007/s00213-023-06444-1. Epub 2023 Aug 14.
Rodent vendors are often utilized interchangeably, assuming that the phenotype of a given strain remains standardized between colonies. Several studies, however, have found significant behavioral and physiological differences between Sprague Dawley (SD) rats from separate vendors. Prepulse inhibition of startle (PPI), a form of sensorimotor gating in which a low-intensity leading stimulus reduces the startle response to a subsequent stimulus, may also vary by vendor. Differences in PPI between rat strains are well known, but divergence between colonies within the SD strain lacks thorough examination.
We explored intrastrain variation in PPI by testing SD rats from two vendors: Envigo and Charles River (CR).
We selected drugs acting on four major neurotransmitter systems that have been repeatedly shown to modulate PPI: dopamine (apomorphine; 0.5, 1.5, 3.0 mg/kg), acetylcholine (scopolamine; 0.1, 0.5, 1.0 mg/kg), glutamate (dizocilpine; 0.5, 1.5, 2.5 mg/kg), and serotonin (2,5-Dimethoxy-4-iodoamphetamine, DOI; 0.25, 0.5, 1.0 mg/kg). We determined PPI and startle amplitude for each drug in male and female Envigo and CR SD rats.
SD rats from Envigo showed dose-dependent decreases in PPI after apomorphine, scopolamine, or dizocilpine administration, without significant effects on startle amplitude. SD rats from CR were less sensitive to modulation of PPI and/or more sensitive to modulation of startle amplitude, across the three drugs.
SD rats showed vendor differences in sensitivity to pharmacological modulation of PPI and startle. We encourage researchers to sample rats from separate vendors before experimentation to identify the most suited source of subjects for their specific endpoints.
啮齿动物供应商经常互换使用，假设特定品系的表型在不同品系之间保持标准化。然而，有几项研究发现，来自不同供应商的 Sprague Dawley（SD）大鼠之间存在显著的行为和生理差异。起始惊吓的前脉冲抑制（PPI）是一种感觉运动门控形式，其中低强度的先导刺激会降低对后续刺激的惊吓反应，也可能因供应商而异。不同大鼠品系之间的 PPI 差异是众所周知的，但 SD 品系内的品系差异缺乏彻底的检查。
我们通过测试来自两个供应商的 SD 大鼠（Envigo 和 Charles River（CR））来探索 PPI 中的品系内变异。
我们选择了作用于四个主要神经递质系统的药物，这些药物已被反复证明可以调节 PPI：多巴胺（阿朴吗啡；0.5、1.5、3.0mg/kg）、乙酰胆碱（东莨菪碱；0.1、0.5、1.0mg/kg）、谷氨酸（地卓西平；0.5、1.5、2.5mg/kg）和 5-羟色胺（2,5-二甲氧基-4-碘苯丙胺，DOI；0.25、0.5、1.0mg/kg）。我们确定了雄性和雌性 Envigo 和 CR SD 大鼠中每种药物的 PPI 和惊吓幅度。
Envigo 的 SD 大鼠在给予阿朴吗啡、东莨菪碱或地卓西平后，PPI 呈剂量依赖性下降，而对惊吓幅度无显著影响。CR 的 SD 大鼠对 PPI 的调节敏感性较低，或对三种药物中惊吓幅度的调节敏感性较高。
SD 大鼠在对 PPI 和惊吓的药物调节的敏感性方面存在供应商差异。我们鼓励研究人员在实验前从不同供应商中取样大鼠，以确定最适合其特定终点的研究对象来源。
