This is the first year of this project and has been taking place while the laboratory has been in the process of starting up. During this year, we have written and had approved the ASP that allows this work to take place, and have completed a pilot study that has produced results to be presented at the annual Neuroscience meeting in November. Furthermore, we have begun the full, long-term training experiment that should be completed by the end of December 2013. We will be training 12 animals over a period of 6-8 weeks to acclimate to MRI restraint and noise, and comparing the sensory and behavioral results to those from 12 animals trained for only 3 days. We will compare these groups of animals to groups that have received the same handling experiences over the same time frames, but will not have experienced any MRI restraint or noise. Pilot Study: Three days of MRI restraint training for imaging of awake rats causes stress-induced analgesia and decreases in exploratory behavior.
Aim : Functional MRI is used in humans to study cognitive and emotional processes, including pain. In order to conduct similar studies in rodents, the animals must be awake and conscious during scanning. Since the restraint and loud noises of MRI can cause stress and alter neural responsiveness, investigators have exposed rats to 3 days of restraint and noise habituation before scanning. Nevertheless, it has not been determined whether such methods normalize pain and emotional behaviors. Here we examine the effect of 3 daily sessions of restraint and noise on pain sensitivity and emotional behavior. Methods: 12 male rats (250-300g, Charles River Laboratories) were acclimated to the animal facility for 3 days. On the 4th, 5th and 6th days, rats were subject to either MRI restraint and loud scanner noise, or exposure to the apparatus and quiet scanner noise (6 animals in each group) for 30 minutes per day. Restrained animals were placed in a fabric snuggle with head and tail protruding, and strapped into a Perspex MRI cradle, and non-restrained animals were exposed to and allowed to explore the restraint apparatus. On the 7th day, thermal sensitivity was measured with the Hargreaves apparatus, and on the 8th day, rats were tested for 5 minutes in the elevated zero maze. Results: Restrained animals had longer thermal withdrawal latencies than non-restrained controls (p=0.02), consistent with stress-produced analgesia. There were no differences between groups on classic anxiety-like behavior outcome measures (time spent on/entries into open sections;p>0.05) but restrained animals spent less time at the boundary of the arms, suggesting a decrease in exploratory behavior (p=0.02). Conclusions: These results show that MRI restraint training performed over 3 days is not sufficient to normalize pain and emotional behaviors in rats, but rather may cause stress-induced analgesia and decreases in exploration in rats. Researchers wishing to perform awake MRI imaging on rats should be aware that MRI training may produce stressed animals, potentially confounding imaging studies.
|Low, Lucie A; Bauer, Lucy C; Pitcher, Mark H et al. (2016) Restraint training for awake functional brain scanning of rodents can cause long-lasting changes in pain and stress responses. Pain 157:1761-72|