Effects of antidepressant treatments on BDNF expression
Antidepressant Treatment | Dosage and Modalities | Cerebral Area, Technique, Measure | Major Findings | Study |
|---|---|---|---|---|
| Electroconvulsive treatment | Acute: a single electrostimulation; chronic: 10 days | FCX, HC; in situ hybridization, Northern blot; BDNF and trkB mRNA | Increase of BDNF mRNA after both acute and chronic ECT in FCX and HC | Nibuya et al. (1995) |
| Acute: a single electrostimulation; chronic: 10 days | Several brain areas; in situ hybridization; BDNF mRNA | Effects of both acute and chronic ECT were most prominent on exon I and II containing BDNF mRNAs in hippocampal and cortical subfields; chronic ECT enhanced acute induction of exon I, II, and IV mRNAs | Dias et al. (2003) | |
| Acute: a single electrostimulation; chronic: 10 days | Several brain areas; ELISA; BDNF protein level | Chronic ECT increased the amount of BDNF protein in all brain regions assessed, producing the highest overall increase in the entorhinal cortex and septum | Altar et al. (2003) | |
| Chronic: 10 days | FCX, HC; in situ hybridization, ELISA; BDNF mRNA and protein level | ECT significantly increased BDNF mRNA in DG and BDNF protein in both FCX and HC | Jacobsen and Mork (2004) | |
| Fluoxetine | 5 mg/kg; acute: 1 day i.p.; chronic: 21 days | FCX, HC; in situ hybridization, Northern blot; BDNF and trkB mRNA | Chronic FLX administration increased expression of BDNF and trkB mRNA in HC but not in FCX | Nibuya et al. (1996) |
| 3 mg/kg; 1, 14 days; osmotic minipumps | Several brain areas; in situ hybridization, histochemistry; BDNF mRNA | Acute FLX treatment increased BDNF mRNA in frontoparietal cortex and inferior olive but reduced it in HC; chronic FLX treatment decreased BDNF mRNA in HC; BDNF mRNA increased only in pontine nuclei | Miró et al. (2002) | |
| 10 mg/kg; acute: single injection i.p.; chronic: 14 days i.p.; rats sacrificed 4 and 24 h after last injection | FCX, HC; in situ hybridization; BDNF mRNA | FLX decreased BDNF mRNA in HC 4 h after both acute and chronic treatment, whereas it up-regulated BDNF mRNA only 24 h after chronic drug treatment; no changes found in FCX | Coppell et al. (2003) | |
| 5 mg/kg; acute: single injection i.p.; chronic: 21 days i.p. | Several brain areas; in situ hybridization; BDNF mRNA | Acute FLX induced region-specific decreases in distinct exon-specific BDNF transcript; chronic FLX administration did not have significant effects on specific BDNF transcripts | Dias et al. (2003) | |
| 20 mg/kg; acute: single injection i.p.; chronic: 4 days, 2 and 3 weeks | Several brain areas; ELISA; BDNF protein level | FLX did not elevate BDNF protein levels in HC | Altar et al. (2003) | |
| 20 mg/kg; acute: single injection i.p.; chronic: 3 weeks, i.p. | Cortex, HC; in situ hybridization, histochemistry, Western blot; TrkB phosphorylation and protein level BDNF mRNA | Acute and chronic FLX treatment increased trkB autophosphorylation without modifying total levels; no change in BDNF mRNA level after acute FLX administration | Saarelainen et al. (2003) | |
| 10 mg/kg; acute: single administration p.o.; time course: 4, 7, 14, and 21 days p.o. | Brain section; in situ hybridization, immunocytochemistry, ELISA; BDNF mRNA and protein level | Single FLX administration had no effect on BDNF mRNA and protein level; 4 days of FLX decreased BDNF mRNA in several brain regions, and significantly in CA1, CA3, medial habenular, and paraventricular thalamic nuclei; 7 days of FLX increased BDNF mRNA nonsignificantly, whereas 14 days significantly increased BDNF mRNA; BDNF immunoreactivity was slightly lower at 4 and 7 days of FLX treatment—at 14, days there was a trend toward an increase in CA3; a significant increase in BDNF immunoreactivity was detected in CA1 and DG after 21 days of FLX | De Foubert et al. (2004) | |
| 10 mg/kg; 14 days i.p.; wt and tg mice with impaired GR function | CA1, CA3, DG; in situ hybridization; BDNF mRNA | Basal expression of BDNF mRNA not significantly different between wt and tg mice with impaired GR function; FLX significantly up-regulated BDNF mRNA in DG and CA3 of tg mice; in wt animals, chronic FLX treatment provoked no significant changes in any hippocampal region | Vinet et al. (2004) | |
| Sertraline | 10 mg/kg; acute: 1 day i.p.; chronic: 21 days i.p. | FCX, HC; in situ hybridization, Northern blot; BDNF and trkB mRNA | Increase of BDNF and trkB mRNA after chronic sertraline treatments in HC | Nibuya et al. (1995) |
| 5 mg/kg; acute: single injection i.p.; chronic: 14 days i.p.; rats sacrificed 4 and 24 h after last injection | FCX, HC; in situ hybridization; BDNF mRNA | Sertraline down-regulated BDNF expression at 4 h after the last injection but up-regulated it in HC 24 h after chronic treatment; 4 h after a single injection of sertraline, a decrease in BDNF mRNA was observed in HC; no changes found at 24 h after drug; neither single nor repeated injections of sertraline influenced BDNF mRNA in FCX | Coppell et al. (2003) | |
| Paroxetine | 5 mg/kg; acute: single injection i.p.; chronic: 14 days i.p.; rats sacrificed 4 and 24 h after last injection | FCX, HC; in situ hybridization; BDNF mRNA | Paroxetine down-regulated BDNF expression at 4 h after the last injection but up-regulated it in HC 24 h after chronic treatment; 4 h after a single injection of paroxetine, a decrease in BDNF mRNA was observed in HC; no changes found at 24 h postdrug | Coppell et al. (2003) |
| Escitalopram | 10 mg/kg; osmotic minipumps; 3 weeks | FCX, HC; in situ hybridization, ELISA; BDNF mRNA and protein level | No significant effect on BDNF mRNA observed in both FCX and CA3 after escitalopram treatments; escitalopram had no significant effects on BDNF mRNA in DG; escitalopram significantly decreased BDNF protein expression | Jacobsen and Mork (2004) |
| Desipramine | 15 mg/kg; acute: 1 day i.p.; chronic: 21 days i.p. | FCX, HC; in situ hybridization, Northern blot; BDNF and trkB mRNA | Increase of BDNF and trkB mRNA in HC after chronic treatment | Nibuya et al. (1995) |
| 15 mg/kg; rolipram (1.25 mg/kg); Ro 20-1724 (12.5 mg/kg); time course: 1, 7, 14, and 21 days i.p. | HC; in situ hybridization, Northern blot; BDNF mRNA | Acute, short-term, and chronic administration of either desipramine or a PDE4 inhibitor alone did not influence BDNF mRNA levels; chronic coadministration of a PDE4 inhibitor and desipramine significantly increased BDNF mRNA; BDNF mRNA levels increased in the major subfields of HC after coadministration of a PDE4 inhibitor and desipramine | Fujimaki et al. (2000) | |
| 10 mg/kg; acute: single injection i.p.; chronic: 14 days i.p.; rats sacrificed 4 and 24 h after last injection | FCX, HC; in situ hybridization; BDNF mRNA | No changes in BDNF expression found after single or repeated administration of desipramine both at 4 and 24 h postdrug | Coppell et al. (2003) | |
| 15 mg/kg; acute: single injection i.p.; chronic: 21 days i.p. | Several brain areas; in situ hybridization; BDNF mRNA | Acute desipramine induced region-specific decreases in distinct exon-specific BDNF transcript; chronic desipramine treatment enhanced exon III mRNAs in discrete hippocampal and cortical subfields | Dias et al. (2003) | |
| 15 mg/kg; acute: single injection i.p.; chronic: 4 days, 2 and 3 weeks | Several brain areas; ELISA; BDNF protein level | Desipramine did not elevate BDNF protein levels in HC | Altar et al. (2003) | |
| 10 mg/kg; 14 days i.p.; wt and tg mice with impaired GR function | CA1, CA3, DG; in situ hybridization; BDNF mRNA | Basal expression of BDNF mRNA was not significantly different between wt and tg mice with impaired GR function; DMI significantly up-regulated BDNF mRNA in DG of impaired GR function mice; in wt animals, chronic treatment provoked no significant changes in any hippocampal region | Vinet et al. (2004) | |
| 10 mg/kg i.p; 3 weeks | FCX, HC; in situ hybridization, ELISA; BDNF mRNA and protein level | No significant effect on BDNF mRNA observed in either FCX or CA3 after treatment; desipramine significantly increased BDNF mRNA in DG; desipramine did not modify BDNF protein level in any examined region | Jacobsen and Mork (2004) | |
| Imipramine | 15 mg/kg; acute: 1 day i.p.; chronic: 21 days i.p. | FCX, HC; in situ hybridization, Northern blot; BDNF and trkB mRNA | Increase of BDNF mRNA in HC after chronic imipramine treatment; increase of trkB after chronic treatment | Nibuya et al. (1995) |
| 15 mg/kg; acute: 1 day i.p.; chronic: 21 days i.p.; rolipram (2 mg/kg): 10 days | FCX, HC; in situ hybridization, Northern blot; BDNF and trkB mRNA | Chronic administration of PDE inhibitors (rolipram and papaverine) significantly increased BDNF and trkB mRNA in HCl; coadministration of imipramine and rolipram for 7 days up-regulated BDNF mRNA | Nibuya et al. (1996) | |
| 15 mg/kg; 20 days i.p.; ± physical activity | HC; in situ hybridization; BDNF mRNA | No effect with imipramine alone; potentiation of BDNF mRNA expression by combination of physical activity and imipramine | Russo-Neustad et al. (1999) | |
| 30 mg/kg; acute: single injection i.p.; chronic: 3 weeks i.p. | Cortex, HC; in situ hybridization, histochemistry, Western blot; TrkB phosphorylation and protein level, BDNF mRNA | Acute and chronic treatment increased trkB autophosphorylation without modifying total levels; no change in BDNF mRNA level after acute administration | Saarelainen et al. (2003) | |
| 1.25–10 mg/kg; ± Rolipram: 1.25 mg/kg; acute: single injection i.p.; chronic: 10 days i.p. | FCX, HC, striatum; ELISA; BDNF protein level | BDNF protein levels were significantly lower in FCX and HC of LH rats than in control rats; chronic treatment with imipramine or rolipram led to a nonsignificant trend toward an increase in BDNF levels; coadministration of imipramine and rolipram significantly increased BDNF protein level in FCX and HC; acute treatment with either drug alone or in combination did not influence BDNF protein levels in LH rats | Itoh et al. (2004) | |
| Amitriptyline | 5 and 10 mg/kg; 21 days i.p. | HC; immunohistochemistry; BDNF protein | At 5 mg/kg, amitriptyline increased BDNF immunostaining in hippocampal pyramidal neurons; the higher dose of amitriptyline did not affect BDNF immunolevels | Xu et al. (2003) |
| Tranylcypromine | 7.5 mg/kg; acute: 1 day i.p.; chronic: 21 days | FCX, HC; in situ hybridization, Northern blot; BDNF and trkB mRNA | Chronic TCP administration increased the expression of BDNF and trkB mRNA in HC but not in FCX | Nibuya et al. (1996) |
| 7.5 mg/kg; ± physical activity; 20 days i.p. | HC; in situ hybridization; BDNF mRNA | Increase of BDNF mRNA with TCP in several HC areas; potentiation of BDNF mRNA density by combination of physical activity and antidepressant | Russo-Neustad et al. (1999) | |
| 7.5 mg/kg; ± physical activity; 2, 7, and 20 days i.p. | HC; in situ hybridization; expression of specific BDNF transcripts (exon I and II), BDNF mRNA | TCP in a short-term treatment led to a significant increase in exon I; chronic TCP increased exon I levels in DG and CA1 but did not modifiy exon II levels; longterm physical activity upregulated transcription of BDNF mRNA containing exons I and II; combination of antidepressant and physical activity may accelerate and increase the amount of BDNF transcription | Russo-Neustad et al. (2000) | |
| 5 mg/kg; acute: single injection i.p.; chronic: 14 days i.p.; rats sacrificed 4 and 24 h after last injection | FCX, HC; in situ hybridization; BDNF mRNA | 4 h after a single injection of TCP, a decrease in BDNF mRNA was observed in HC; no changes found at 24 h postdrug; TCP down-regulated BDNF expression at 4 h after the last injection but up-regulated it 24 h after chronic treatment in HC; neither single nor repeated injections of TCP influenced BDNF mRNA in FCX | Coppell et al. (2003) | |
| 7, 5, and 10 mg/kg; acute: single injection i.p.; chronic: 21 days i.p. | Several brain areas; in situ hybridization; BDNF mRNA | Acute TCP induced region-specific decreases in distinct exon-specific BDNF transcripts; chronic TCP treatment enhanced exon II and exon III mRNAs, respectively, in discrete hippocampal and cortical subfields | Dias et al. (2003) | |
| 8–10 mg/kg; acute: single injection i.p.; chronic: 4 days, 2 and 3 weeks | Several brain areas; ELISA; BDNF protein level | Acute treatment with TCP failed to alter BDNF, whereas BDNF protein levels significantly increased after 2 and 3 weeks of treatment in FCX and neostriatum, respectively, but not in HC | Altar et al. (2003) | |
| Venlafaxine | 5 and 10 mg/kg; 21 days i.p. | HC; Immunohistochemistry; BDNF protein | At 5 mg/kg, venlafaxine increased BDNF immunostaining in hippocampal pyramidal neurons; at 10 mg/kg, venlafaxine decreased BDNF immunostaining in all HC subareas | Xu et al. (2003) |
| Mianserin | 10 mg/kg; acute: 1 day i.p.; chronic: 21 days i.p. | FCX, HC; in situ hybridization, Northern blot; BDNF and trkB mRNA | Chronic treatment with mianserin increased BDNF mRNA in HC; chronic mianserin did not affect trkB | Nibuya et al. (1995) |
| 10 mg/kg; acute: single injection i.p.; chronic: 14 days i.p.; rats sacrificed 4 and 24 h after last injection | FCX, HC; in situ hybridization; BDNF mRNA | No changes in BDNF expression found after single or repeated administration of mianserin, both at 4 and 24 h postdrug | Coppell et al. (2003) | |
| Maprotiline | 10 mg/kg; acute: single injection i.p.; chronic: 14 days i.p.; rats sacrificed 4 and 24 h after last injection | FCX, HC; in situ hybridization; BDNF mRNA | No changes in BDNF expression found after single or repeated administration of maprotiline, both at 4 and 24 h postdrug | Coppell et al. (2003) |
FCX, frontal cortex; HC, hippocampus; GR, glucocorticoid receptor; Ro 20-1724, 4-[(3-butoxy-4-methoxyphenyl)-methyl]-2-imidazolidinone; PDE, phosphodiesterase.