Tel.+49 30 838 53221 Fax.+49 30 838 53112
Strain differences make the development of new anxiolytics more difficult. Conflicting effects of serotonergic drugs were observed, even when identical animal tests were used.Hence, the aim of this study was to investigate in more detail the influence of strain or stock differences on the baseline anxiety related behaviour of rats. The effects different anxiety levels have on the application of various anxiolytics and the differences between strains and stocks in the metabolism of these anxiolytics were investigated. Furthermore, the question of whether there are differences in the central serotonergic (5-HT) system was explored, because 5-HT plays a major role in the creation .To get an overall picture of theinfluence of breeding conditions on anxiety related behaviour of rats, three stocks of Fischer rats (Winkelmann, Schönwalde and Charles River) bred in our animal unit, were compared to Fischer rats received directly from the same breeders. For these experiments the elevated plus maze-, black and white box- and modified open field-test were chosen. The results show that breeding conditions really influence the anxiety related behaviour of rats. Raised under our breeding cond. The pharmacological investigations were carried out on two different Wistar stocks (Winkelmann and BgVV) and one Fischer strain from Winkelmann. For the experiments the same animal models were used as described above. The anxiolytic substances, diazepam, 8?OH-DPAT and ritanserin, were chosen. In all animal models the Wistar/Winkelmann rats proved to be less anxious than the Fischer/Winkelmann and Wistar/BgVV rats. Whereas Wistar/BgVV and Fischer/Winkelmann rats behaved in a similar fashion. Diazepam had an.In another experiment the blood plasma concentrations of diazepam and three of its metabolites, n?desmethyldiazepam, temazepam and oxazepam, were measured at the time the behavioural tests took place. The con
centrations of these four substances were significantly higher in the Fischer/Winkelmann rats in comparison to both Wistar stocks. There were no differences between the two stocks of Wistar rats. N-desmethyldiazepam and temazepam were equally abundant in the Fischer/Winkelmann rats, whereas in both sto.Finally, the levels of 5-HT were measured in the prefrontal cortex, the hippocampus and in the median/dorsal raphe. In the more anxious Fischer/Winkelmann rats, the level of 5-HT was significantly higher in the prefrontal cortex as well as in the hippocampus compared to both Wistar stocks. The levels of 5-HT in the hippocampus and the median/dorsal raphe were higher in the Wistar/BgVV rats than in the Wistar/Winkelmann rats. The application of 2,0 mg/kg diazepam i.p. had a different effect on the central l.In sum, these results show that there is a large impact of breeding conditions as well as strain and stock differences on anxiety related behaviour. Moreover, differences in the baseline behaviour might have an influence on the effects of pharmacotherapeutics. Additionally, it appears that the different effects of diazepam can be traced back to a different metabolism. Differences in the central serotonergic system seem to reflect a difference in the anxiety related behaviour of the examined rat strains and.Therefore, strain and stock differences should be taken into consideration in future investigations and it is recommended to cite exactly in the description of a method the source of the animals.