ArticlesOntogeny of Muscarinic Cholinergic Supersensitivity in the Flinders Sensitive Line Rat
Section snippets
Animals
FSL and FRL male and females rats were from the 40th to 49th generations bred and maintained in the School of Biological Sciences, The Flinders University of South Australia. Each new generation of rats was screened for behavioral sensitivity to muscarinic agonists and the subsequent generation of FSL rats obtained by mating the 10 most “sensitive” males and females, while the 10 most “resistant” males and females were mated to produce the next generation of FRL rats. Breeding pairs were
Baseline Measures
There were age, F(19, 2244) = 2571.64, p < 0.001, gender, F(1, 2244) = 1402.17, p < 0.001, and line, F(1, 2244) = 20.71, p < 0.001, effects on the changes in body weight. Interaction effects were apparent between (a) age and line, F(19, 2244) = 1.62, p < 0.05, where both male and female FSL rats weighed more than their FRL counterparts through to P51 and less thereafter; and (b) gender and age, F(19, 2244) = 99.64, p < 0.001. The expected gender difference did not emerge until P31 and increased
Discussion
The main aim of this study was to examine the ontogeny of muscarinic sensitivity in the FSL rat, a model of human depression that was selectively bred for increased cholinergic function. It is now well recognized that humans with depressive disorders are more sensitive to the behavioral and physiological effects of muscarinic drugs than are nondepressed controls 6, 25, 55, 62. Controversy remains as to whether this altered cholinergic function is a cause or a consequence of the depressive
Acknowledgements
This work was supported by a Dora Lush National Health and Medical Research Council Biomedical Postgraduate Scholarship (927435) to L.C.D. and funds provided by the Flinders University Research Budget. The authors would like to greatfully acknowledge Cheryl Greaves and Leah Nesbitt for their excellent care and maintenance of the animals and George Daws for research assistance. Our thanks to Drs Grant Schiller and Joe Orbach for valuable discussions and their assistance with this study.
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