| Major depressive disorder is a devastating disease characterized by intense and prolonged sadness and feelings of hopelessness and worthlessness. While developments in drug therapy have provided some insight into the mechanisms underlying depression, investigations employing animal models have provided another strategy for studying the neurobiology of depression. The first generation of these models evolved to evaluate the therapeutic potential of novel drugs, and included the reserpine reversal test, forced swimming test, and the brain-stimulation reward (BSR) procedure. The rationale in the case of the latter was that since one of the core symptoms of depression is a decreased capacity to experience pleasure, interventions that relieve these symptoms in humans will enhance reward transmission; in animals, this was interpreted from decreases in thresholds for BSR. In the first experiment, we evaluated the effects of paroxetine, an antidepressant of the selective serotonin reuptake inhibitor class, on BSR thresholds and observed only modest decreases in thresholds. These results mimicked the minimal mood altering effects that antidepressants are reported to have in “normal” individuals. Next, as a means of inducing a depressive state in rats, the chronic mild stress (CMS) procedure, developed to model anhedonia, a core symptom of depression, was employed in the subsequent experiments. Its consequences were measured on several indices of depressive behaviours, sucrose consumption (1 and 24h intake and preference), BSR thresholds, and the forced swim test. Genetic variation was considered by comparing male and female rats of two outbred strains. While CMS produced little change in BSR thresholds, its effects on sucrose consumption were varied; in male rats, we observed an initial reduction in 1h sucrose intake in Long Evans exclusively, while a CMS-induced reduction on the 24h intake measure was evident in both strains of female rats, with a greater effect in the Sprague-Dawley group. In evaluating the effects of CMS on forced swimming behaviour, we saw no group or strain difference in the female rats and a notable strain difference in male rats. Long Evans animals with a history of stress significantly reduced the duration of the test engaged in escape-type behaviours on the second exposure to forced swim, as would be expected in animals experiencing learned helplessness, a behaviour characteristic of depressed individuals. (Abstract shortened by UMI.)... |
