Ketamine elicits sustained antidepressant-like activity via a serotonin-dependent mechanism.
Saved in:
| Title: | Ketamine elicits sustained antidepressant-like activity via a serotonin-dependent mechanism. |
|---|---|
| Authors: | Gigliucci, Valentina, O'Dowd, Grainne, Casey, Sheena, Egan, Danielle, Gibney, Sinead, Harkin, Andrew |
| Source: | Psychopharmacology. Jul2013, Vol. 228 Issue 1, p157-166. 10p. 4 Graphs. |
| Subjects: | Ketamine, Antidepressants, Serotonin, Controlled release drugs, Effect of stress on animals, Hydroxytryptophan, Chlorophenylalanine, Scientific observation |
| Abstract: | Rationale: Behavioural antidepressant-like effects of ketamine have been reported in the forced swimming test (FST). The mechanisms mediating such effects are unknown. Objectives: As serotonin (5-HT) is an important transmitter mediating antidepressant responsiveness in the FST, the influence of 5-HT depletion on the antidepressant-like effect of ketamine was assessed. Methods: The effect of ketamine (25 mg/kg, i.p., 1 or 24 h prior to test) was assessed in the FST in naive rats or animals subjected to 5-HT depletion, repeated stress or following a combination of 5-HT depletion and stress. Endogenous 5-HT was depleted using the tryptophan hydroxylase inhibitor para-chlorophenylalanine (3 × 150 mg/kg, i.p.). Stress was induced by physical restraint (2 h/day for 10 days). Results: In naive rats, ketamine administered 24 or 1 h prior to test produced a characteristic antidepressant-like reduction in immobility time in the FST. Depletion of 5-HT blocked this reduction in immobility when ketamine was administered 24 h prior FST, indicative of 5-HT dependency. The increase in immobility provoked by repeated restraint stress (2 h/day for 10 days) was blocked by ketamine when administered 24 h prior to FST, but this effect dissipated when animals were subjected to 5-HT depletion. Conclusions: These observations are consistent with a role for 5-HT in mediating sustained antidepressant activity of ketamine in the FST. Molecular and cellular changes induced by ketamine may produce a rapid adaptation of 5-HT transmission which underlies the antidepressant response. [ABSTRACT FROM AUTHOR] |
| Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
Be the first to leave a comment!
