Mitra Swarup, Bult-Ito Abel
Departments of Chemistry & Biochemistry.
IDeA Network of Biomedical Research Excellence (INBRE), University of Alaska Fairbanks, Fairbanks, Alaska, USA.
Behav Pharmacol. 2018 Jun;29(4):299-305. doi: 10.1097/FBP.0000000000000348.
The current study evaluated the role of strain and compulsive trait differences in response to fluvoxamine, a common obsessive-compulsive disorder (OCD) drug, in two different mouse strains (BIG1 and BIG2) with a spontaneous compulsive-like phenotype. For compulsive-like nest-building behavior, dose-dependent attenuation of nesting by fluvoxamine was observed for the BIG1 compulsive-like strain during the first hour after administration. No significant differences were found for the BIG2 strain during the first hour, although a dose-dependent trend similar to that in the BIG1 strain was observed. Fluvoxamine dose dependently decreased the number of marbles buried in both strains 1 h after administration. For anxiety-like behaviors in the open field, no significant drug effects were found for the latency to leave the center and the number of line crossings. Significant strain differences were observed, with the BIG2 strain showing higher anxiety-like behaviors and reduced locomotor activity compared with the BIG1 strain. Consequently, this study adds predictive validity to our mouse model of OCD, whereas the anxiety-like differences between the strains add heterogeneity to our mouse model, similar to the heterogeneity observed in OCD.
本研究评估了在两种具有自发强迫样表型的不同小鼠品系(BIG1和BIG2)中,品系差异和强迫特质差异在对氟伏沙明(一种常见的强迫症药物)反应中的作用。对于强迫样筑巢行为,在给药后的第一个小时内,观察到氟伏沙明对BIG1强迫样品系的筑巢行为有剂量依赖性的减弱作用。在第一个小时内,BIG2品系未发现显著差异,尽管观察到与BIG1品系相似的剂量依赖性趋势。给药1小时后,氟伏沙明剂量依赖性地减少了两个品系中埋藏弹珠的数量。对于旷场试验中的焦虑样行为,离开中心的潜伏期和穿越线的数量未发现显著的药物效应。观察到显著的品系差异,与BIG1品系相比,BIG2品系表现出更高的焦虑样行为和更低的运动活性。因此,本研究为我们的强迫症小鼠模型增加了预测效度,而品系间的焦虑样差异为我们的小鼠模型增加了异质性,类似于在强迫症中观察到的异质性。