Measuring social interactions in colour-marked rats
adapted to a reversed daylight cycle:
ultraviolet lighting and fluorescent markers
help avoid problems with colour distinction in dim light
J.P. Johansson and M.L. Carlsson
Institute of Clinical Neuroscience, Göteborg University, Göteborg, Sweden
The symptoms of schizophrenia can be divided into positive, negative and cognitive. Positive symptoms are characteristics added to the normal state, including hallucinations, delusions and thought disorders. Negative symptoms refer to lost functions, and comprise social withdrawal, flattened affect and apathy. Classic neuroleptics are effective in relieving positive symptoms, but affect negative or cognitive symptoms to a lesser extent. Furthermore, these drugs have serious extrapyramidal side effects. There are a few atypical antipsychotic drugs that alleviate a broader spectrum of symptoms, but there is still an urgent need for more effective drugs with fewer side effects.
Hypoglutamatergia in rodents, induced by the non-competitive NMDA receptor antagonist MK-801, results in a characteristic behavioral pattern that serves as a powerful model for schizophrenia. The aspect of behavior most widely studied in this context is hyperactivity, which is believed to model positive symptoms. Increased computer power and refined methods for behavioral studies have made it feasible and cost-effective to measure a large number of other aspects of behavior, such as stereotypies and social behavior, through automated video tracking [1]. Hypoglutamatergia-induced social withdrawal in rats is believed to serve as a model for negative symptoms.
To meet our needs for a more complete model for schizophrenia, we have extended our use of EthoVision to measuring social interactions between two rats. The rats are videotaped from above, and the animals' movements are tracked by computer analysis. EthoVision offers two different means of identifying animals tracked in the same arena: by surface area or by colour. In our system, identifying rats by measuring surface area results in errors that must be corrected manually. Thus, we decided to use colour marking for identification. Since we keep the animals in a reversed light/dark cycle and perform the experiments in dim light conditions during the rats' active phase, detecting colour becomes a problem. Therefore, we mark the rats with fluorescent dyes (Net-Tex Agricultural Ltd.) and illuminate the arenas with UV-light (350-400 nm, 2 x 1.2 W). The fluorescent spots on the rats appear as patches of different colour against a dark background. The software can then effectively separate the two animals. The resulting tracks form the basis for a vast number of parameters describing many aspects of behavior. EthoVision is capable of calculating most parameters, but additional and modified parameters may be calculated using other software, such as MatLab (The MathWorks, Inc.).
In conclusion, behavioral studies in rats serve as a powerful tool to evaluate putative pharmacological treatments for schizophrenia. Novel drug candidates are compared in this model with existing classic and newer antipsychotic drugs, with respect to their capacity to alleviate both positive and negative symptoms.
References
Paper presented at Measuring Behavior 2002 , 4th International Conference on Methods and Techniques in Behavioral Research, 27-30 August 2002, Amsterdam, The Netherlands