The intent of the present series of experiments was to better understand the events that produce a rapid adaptation of beta adrenergic and serotonin-2 (5-HT2) receptors when imipramine treatment and forced swim are combined in Sprague-Dawley rats. Beta adrenergic and 5-HT2 receptors were evaluated at specific stages of the forced swim test with and without imipramine treatment. Rapid changes in receptor binding were observed in saline-treated rats during specific stages of the test. The changes observed during forced swim could not be attributed to the transport-novelty that occurs during forced swim. Binding for both monoamine receptors was reduced in hippocampus and frontal cortex before the test swim in imipramine-treated rats as they were 10 min, 3 hr and 24 hr after the test swim. The increase in corticosterone induced by the second forced swim was not altered by imipramine, indicating that imipramine was not interfering with this measure of the stress response. In the Fisher-344 rat strain, imipramine did not produce a behavioral change during the test swim. In contrast to this lack of a behavioral change in the Fischer-344 rats, beta adrenergic and 5-HT2 receptor down-regulation was facilitated in this rat strain, similar to that found in imipramine-treated Sprague-Dawley rats subjected to swim. This latter finding suggests that beta adrenergic or 5-HT2 receptor adaptation alone is insufficient to cause an imipramine-induced behavioral change in the swim test. Studies with specific norepinephrine- and serotonin-uptake inhibitors, nisoxetine and fluoxetine, respectively, indicate that the behavioral effects of imipramine in the forced swim test are dependent upon norepinephrine uptake inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)