Figure 1.
The intrinsic functional activities of YL-0919 on 5-HT1A receptor.
A. The chemical structure of YL-0919. B. C. D. cAMP assays. Both 8-OH-DPAT (10−11∼10−6 M) and YL-0919 (10−11∼10−6 M) concentration-dependently inhibited forskolin-stimulated cAMP formation (B). WAY-100635(0.1 µM) markedly prevented the 8-OH-DPAT (10−11∼10−9 M) (C) and YL-0919 (10−11∼10−9 M) (D) mediated inhibition of forskolin-stimulated cAMP formation. PC12 cells expressing 5-HT1A receptors were incubated in the presence of 0.5 mM IBMX, 10 µM forskolin and, different concentrations of drugs. Data (presented as mean ±SEM) were representative of four distinct experiments performed in triplicate. **p<0.01 versus the same concentration of 8-OH-DPAT or YL-0919.
Table 1.
The specific parameters in binding and uptake assays.
Figure 2.
The effects of YL-0919 in rats exposed to 4-week stress procedure.
A. The outline of design for CUS and behavioral tests. B.C. The effects of YL-0919 and fluoxetine on the number of crossing and rearing. The number of crossing and rearing in stress-vehicle group were significantly decreased after 4-week exposure to chronic unpredictable stress. Daily oral administration of YL-0919 (1.25 or 5 mg/kg) and fluoxetine (10 mg/kg) reversed the inhibition of locomotor activity in CUS rats. D.E. The effects of YL-0919 and fluoxetine on the sucrose preference in rats before (D) and after (E) 4-week stress procedure. Four-week stress procedure caused significant decrease in sucrose preference in stress-vehicle rats compared to control non-stressed rats. Four-week treatment of YL-0919 (1.25, 2.5 mg/kg, p.o.) and fluoxetine (2.5 mg/kg, p.o.) restored the sucrose preference to normal level. F. The effects of YL-0919 and fluoxetine on the latency to begin eating in rats exposed to 4-week stress regime. Long-term treatment of YL-0919 (1.25 or 2.5 mg/kg, p.o.) and fluoxetine (10 mg/kg, p.o.) significantly reduced the latency to begin eating compared with vehicle-stressed rats. Flu, fiuoxetine. Fluoxetine or YL-0919 was administered p.o. prior to stress procedure. Data are presented as means±SEM (n = 8–11/group). **p<0.01, ***p<0.001versus control, #p<0.05, ##p<0.01, ###p<0.001 versus stress.
Table 2.
The chronic unpredictable stress regime.
Table 3.
The affinity of YL-0919 to 5-HT1A receptor and monoamine transporters.
Table 4.
The functional properties of YL-0919 and fluoxetine on SERT.
Figure 3.
The effect of YL-0919 in the behavioral despair paradigms.
YL-0919 produced antidepressant-like effects in TST in mcie (A), FST in mice (B) and FST in rats (C). Veh, vehicle; Flu, fluoxetine; DIM, desipramine. YL-0919, fluoxetine, or desipramine was administered p.o. 60 min prior to the test. Data are presented as means±SEM (n = 10–12/group). *p<0.05, **p<0.01, ***p<0.001 versus vehicle.
Figure 4.
The effect of 5-HT1A receptor in the antidepressant-like of YL-0919.
Coadministration with WAY-100635 (0.3 mg/kg, s.c.) prevented YL-0919 (1.25, 2.5 mg/kg, p.o.)-induced reductions in the immobility time in TST (A) and FST (B) in mice. WAY, WAY-100635; YL, YL-0919. Mice received WAY-100635 and YL-0919 simultaneously; 60 min later, the animal were submitted to the forced swimming. Data are presented as means±SEM (n = 10/group). **p<0.01, ***p<0.001 versus vehicle, ##p<0.01 versus the same dose of YL-0919.
Table 5.
The effect of YL-0919 on locomotor activity in mice and rats.