Figure 5.
Binding to TRKB mediates the plasticity-related effects of antidepressants
(A) Treatment with pravastatin (10 mg/kg/day in the drinking water for 14 days) attenuated the BDNF-induced LTP in the hippocampus of anesthetized rats (F[85,1,290] = 1.484, p = 0.0036, n = 8–9).
(B) Fluoxetine promotes hippocampal neurogenesis in wild-type, but not in TRKB.Y433F mice (n = 7–9; interaction: F[1,30] = 4.691, p = 0.0384). Mice received bromodeoxyuridine (BrdU) injections at day 1, the BrdU incorporation was measured after 3 weeks of fluoxetine treatment (15 mg/kg/day for 21 days in the drinking water, orally [p.o.]).
(C) Fluoxetine (10 mg/kg/day for 28 days, p.o.; n = 6), R,R-HNK (10 mg/kg i.p. injection every second day for 8 days, n = 4), and ketamine (10 mg/kg i.p. injection every second day for 8 days, n = 5) permitted a shift in ocular dominance in adult mice during 7 days of monocular deprivation (paired t test: fluoxetine: t[5] = 2.985, p = 0.0306; R,R-HNK: t[3] = 6.875, p = 0.0063; ketamine: t[4] = 6.517, p = 0.0029). *p < 0.05 between intrinsic signal imaging (IOS) sessions.
(D and E) Fluoxetine (D) and R,R-HNK (E) fail to permit a shift in ocular dominance in TRKB.Y433F mice (fluoxetine: F[1,19] = 256.9, p < 0.0001, n = 9–12; R,R-HNK: F[1,20] = 12.47, p = 0.0021, n = 6/group).
(F) Treatment with fluoxetine induced a shift in ocular dominance in response to 7 days of monocular deprivation, but this effect is prevented by pravastatin (interaction: F[1,10] = 5.221, p = 0.0454, n = 5–6).
(G) R,R-HNK induced a shift in ocular dominance in response to 7 days of monocular deprivation, but this effect is prevented by pravastatin (treatment: F[1,9] = 9.044; p = 0.0148, n = 4–7). ∗p < 0.05 from the control group in the same session, Fisher’s LSD. Data expressed as mean ± SEM. The black groups in plots (F) and (G) are also depicted in (C).