α2-adrenoceptor binding in Flinders-sensitive line compared with Flinders-resistant line and Sprague-Dawley rats

Objectives: Disturbances in the noradrenergic system, including alterations in the densities of alpha(2)-adrenoceptors, are posited to be involved in the pathophysiology of depression. In this study, we investigate the binding of alpha(2)-adrenoceptors in regions relevant to depression in an animal model of depression. Methods: Using in vitro autoradiography techniques and the selective alpha(2)-ligand, [H-3]RX 821002, we investigated the density of alpha(2)-adrenoceptors in female Flinders-sensitive line (FSL) rats, a validated model of depression, and in two traditional control groups - female Flinders-resistant line (FRL) and Sprague-Dawley (SD) rats. Results: The alpha(2)-adrenoceptor density was increased in most regions of the FSL rat brain when compared with SD rats (10% across regions). Moreover, the alpha(2)-adrenoceptor density was further increased in the FRL rats compared with both FSL (10% across regions) and SD rats (24% across regions). Conclusions: The increase in alpha(2)-adrenoceptor binding in cortical regions in the FSL strain compared with the SD control strain is in accord with alpha(2)-adrenoceptor post-mortem binding data in suicide victims with untreated major depression. However, the differences in binding observed in the two control groups were unexpected and suggest the need for further studies in a larger cohort of animals of both sexes.