Implementation of improved postoperative care decreases the mortality rate of operated mice after an abundant 6-hydroxydopamine lesion of nigrostriatal dopaminergic neurons

Abstract

A mouse model of Parkinson’s disease with an abundant lesion of nigrostriatal dopaminergic neurons can be achieved by stereotactic injection of 6-hydroxydopamine into the medial forebrain bundle. However, postoperative mortality can be excessively high without intensive postoperative care. Here, we show that improvements in stereotactic operations and postoperative care result in significant benefits for both animal well-being and research efficiency. Adopting a wide combination of mostly previously described improvements resulted in a decrease of postoperative mortality from 71% to 14% and an increase in successful abundant dopaminergic lesions from 46% to 81%. The techniques adopted are described in detail. In addition, we describe a simple protocol for gradual preoperative handling which can be utilized to decrease animal stress, aggressive and aversive behaviors, and to facilitate postoperative care and other subsequent handling. We propose that the implementation of these improvements greatly decreases the risk of animal suffering and that the improvements are worth adopting in any research group utilizing abundant 6-hydroxydopamine-induced dopaminergic lesions in mice. Suggestions for further improvement are also presented.