The pharmacology of 24-hour behavioural rhythms in mice

• Main Author: Childs, Graham
• Published: University of Bath 1982
• Subjects: 615.1; Pharmacology & pharmacy & pharmaceutical chemistry
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.253536

This study has been a broadly-based attempt to draw parallels between the known psychological disturbances in human beings following physical translocation, with behavioural changes in laboratory mice following alterations in environmental synchronizers (zietgebers). The passive avoidance response was thought to provide a valid model for learning and retention. The response was found to display a significant 24-hour variation and was significantly reduced by phase shift. The reduction was alleviated by chronic benzodiazepine therapy, effects which were not found in preliminary investigations with other classes of psychoactive drugs. Benzodiazepines also exerted facilitatory effects in non-phase shifted subjects, which were maximal in the early light phase. All these properties seemed unique to the benzodiazepines. Significant 24-hour variations were found to exist in a number of other behavioural parameters, namely open-field and locomotor activity, social responsiveness and aggression. Levels of passive avoidance, aggression and open-field behaviour were thought to be determined by endogenous oscillators externally entrained to the environment because a) they displayed either partial or complete independence of environmental manipulations, and b) they required some period of time to re-adjust when the environmental circumstances were changed. Social and motor activity were thought to be largely exogenously controlled variations because they altered immediately in response to environmental manipulations and adjusted immediately to phase shift. This study appears to confirm that "sensitive" psychological parameters can be "desynchronized" whereas the more crude motor responses appear less affected. The study does not provide for the social / physical factors associated with "jet lag" in humans, and constitutes a static analogy to translocation. The study is thought to provide a useful animal model for purely desynchronization-induced psychological disturbances, and that these effects may be modified by chronic benzodiazepine therapy. Furthermore it is clear that susceptibility to this therapy may vary according to the time of administration, and allowances should be made for this.