Effects of Imipramine and Bupropion on the Duration of Immobility of ACTH-Treated Rats in the Forced Swim Test: Involvement of the Expression of 5-HT_2A Receptor mRNA

Abstract

We examined the effect of chronic administration of imipramine and bupropion, monoamine reuptake inhibitors, on the duration of immobility in the forced swim test and serotonin (5-HT) 2A receptor function in the form of 5-HT 2A receptor mRNA levels in rats chronically treated with adrenocorticotropic hormone (ACTH). The immobility-decreasing effect of bupropion without imipramine did not influence the chronic ACTH treatment. The effect on the expression of 5-HT 2A receptor mRNA of chronic ACTH treatment was decreased by bupropion, but not imipramine. These results suggest that bupropion has the effect of reducing immobility time in the forced swim test in the tricyclic antidepressant-resistant depressive model induced by chronic ACTH treatment in rats, and that decreased 5-HT 2A receptor mRNA levels may be involved in this phenomenon.

Chronic imipramine but not bupropion increases arachidonic acid signaling in rat brain: is this related to ‘switching’ in bipolar disorder?

“…Bupropion is thought to act by inhibiting both noradrenalin and dopamine reuptake, but has no significant serotonergic effect 52. Acute or chronic bupropion given to rats had an antidepressant effect by reducing immobility time in the forced swim test,53–55 and improved behavior in another animal model of depression 56. Because imipramine but not bupropion is reported to increase switching in bipolar depressed patients,43,47,57–59 we hypothesized that chronic imipramine but not bupropion would increase markers of AA metabolism, including AA turnover in phospholipids and cPLA 2 expression, in rat brain.…”

Effects of the 5-HT_1A Receptor Agonist Tandospirone on ACTH-Induced Sleep Disturbance in Rats

“…We previously reported that chronic treatment with ACTH increased expression of 5-HT 2A receptor mRNA in the frontal cortex, and enhanced the function of 5-HT 2A receptors in rats. 28,29) Some studies in rats and humans have shown that 5-HT 2A receptor agonists increase wakefulness and inhibit slow-wave sleep (SWS), whereas 5-HT 2A receptor antagonists enhance duration of SWS and EEG low-frequency activity in non-REM sleep. [30][31][32] On the other hand, 5-HT 1A receptors were reported to regulate the activity of the serotonin nervous system, which inhibited the function of 5-HT 2A receptors.…”

Brain energy metabolism is increased by chronic administration of bupropion

“…Damage to the mitochondrial electron transport chain has been suggested to be an important factor in the pathogenesis of a range of psychiatric disorders (29–31) including major depression (42–45). Gardner et al (43) showed a significant decrease in mitochondrial ATP production rates and mitochondrial enzyme ratios in muscles of major depressive disorder patients.…”