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.
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.
Authors: R Bernard; I A Kerman; R C Thompson; E G Jones; W E Bunney; J D Barchas; A F Schatzberg; R M Myers; H Akil; S J Watson Journal: Mol Psychiatry Date: 2010-04-13 Impact factor: 15.992
Authors: Sungho Maeng; Carlos A Zarate; Jing Du; Robert J Schloesser; Joseph McCammon; Guang Chen; Husseini K Manji Journal: Biol Psychiatry Date: 2007-07-23 Impact factor: 13.382
Authors: Ingeborg H Hansen; Claus Agerskov; Lars Arvastson; Jesper F Bastlund; Helge B D Sørensen; Kjartan F Herrik Journal: Eur J Neurosci Date: 2019-04-01 Impact factor: 3.386