Citalopram decreases tryptophan 2,3-dioxygenase activity and brain 5-HT turnover in swim stressed rats.
Journal Title: Pharmacological Reports - Year 2012, Vol 64, Issue 3
Abstract
Background: Selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed antidepressant class today and exert their effects by increasing synaptic concentrations of serotonin (5-HT). The forced swim test (FST) is the most widely used animal test predictive of antidepressant action. Rationale of the present study was to investigate the acute effects of citalopram on hepatic tryptophan metabolism and disposition in rats exposed to FST. Methods: We investigated the effects of acute citalopram (20 mg/kg, ip) administration on rat's behavioral responses in FST paradigm, hepatic tryptophan 2,3-dioxygenase (TDO) activity, serum corticosterone levels and brain regional 5-HT metabolism. Results: Citalopram administered to swim-stressed rats showed a decrease in FST-induced increases in plasma corticosterone concentration and 5-HT turnover in hypothalamus, amygdala and hippocampus. The drug also decreases immobility and increases swimming during the FST. Citalopram administration to unstressed rats increases plasma corticosterone concentration but decreases 5-HT turnover in all three brain areas examined. Conclusions: Our findings support the hypothesis that acute citalopram administration increases tryptophan (by inhibiting TDO activity) availability for 5-HT synthesis and activates serotonergic neurotransmission in limbic brain areas in rats exposed to FST paradigm. The mechanism of action of citalopram in ameliorating social stress related depressive disorder in humans is discussed.
Authors and Affiliations
Iffat Ara, Samina Bano
Keywords
Related Articles
- EP ID EP135292
- DOI -
- Views 84
- Downloads 0
Antiapoptotic action of lithium and valproate.
Lithium and valproate (VPA) have been the most widely prescribed mood stabilizers for the therapy of bipolar disorders (BD) for more than 50 years. However, the precise molecular mechanism of their pharmacological activi...
Inhibitory effects of amantadine on the production of pro-inflammatory cytokines by stimulated in vitro human blood.
Treatment with amantadine (AMA), an N-methyl-D-aspartate (NMDA) receptor antagonist and antidepressant drug, increased the antidepressant activity of subsequent drugs in experimental studies and in patients suffering fro...
Professor Alfons Chodera, Ph.D., M.D. (1925-2005).
Pharmacokinetics of a synthetic interferon inducer amixin in mice.
Pharmacokinetics of amixin, a synthetic interferon inducer, has been studied in mice under intravenous and oral routes of administration. Following oral administration, 80% of the drug was eliminated in the unchanged for...
Mechlorethamine (NTG) effects on the erythrocytic and leukocytic blood parameters during experimentally induced pleuritis in rats.
Background: According to cytotoxic and mutagenic properties, nitrogranulogen (NTG) changes the character of inflammatory reactions. Our previous studies have shown that NTG can enhance immunological defense reactions, be...