Research Article| Volume 54, ISSUE 7, P703-709, October 01, 2003

Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain



      The antidepressant-like effects of brain-derived neurotrophic factor (BDNF) infusions in brain, and the upregulation of BDNF mRNA and its receptor in rats exposed to electroconvulsive seizure (ECS) and antidepressants, suggested a role for increased BDNF protein.


      We measured BDNF protein levels with a two-site enzyme-linked immunosorbent assay (ELISA) in six brain regions of adult male rats that received daily ECS or daily injections of antidepressant drugs.


      The BDNF ELISA method was validated by the 50% loss of BDNF protein in the brains of +/− BDNF knockout mice, the 60%–100% recovery of spiked recombinant BDNF, and by the amounts and regional variations of BDNF measured in the six brain regions. Ten consecutive daily exposures to ECS increased BDNF protein in the parietal cortex (219%), entorhinal cortex (153%), hippocampus (132%), frontal cortex (94%), neostriatum (67%), and septum (29%). BDNF increased gradually in the hippocampus and frontal cortex, with a peak response by the fourth day of ECS. Increases peaked at 15 hours after the last ECS and lasted at least 3 days thereafter. Two weeks of daily injections with the monoamine (MAO)-A and -B inhibitor tranylcypromine (8–10 mg/kg, IP) increased BDNF by 15% in the frontal cortex, and 3 weeks treatment increased it by 18% in the frontal cortex and by 29% in the neostriatum. Tranylcypromine, fluoxetine, and desmethylimipramine did not elevate BDNF in the hippocampus.


      Elevations in BDNF protein in brain are consistent with the greater treatment efficacy of ECS and MAO inhibitors in drug-resistant major depressive disorder and may be predictive for the antidepressant action of the more highly efficacious interventions.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Altar C.A.
        Neurotrophins and depression.
        Trends Pharmacol Sci. 1999; 20: 59-61
        • Altar C.A.
        • Boylan C.B.
        • Fritsche M.
        • Jackson C.
        • Jones B.E.
        • Wiegand S.W.
        • et al.
        Efficacy of brain-derived neurotrophic factor and neurotrophin-3 on neurochemical and behavioral deficits associated with partial nigrostriatal dopamine lesions.
        J Neurochem. 1994; 63: 1021-1032
        • Altar C.A.
        • Cai N.
        • Bliven T.T.
        • Juhasz M.
        • Connor J.R.
        • Acheson A.L.
        • et al.
        Anterograde transport of brain-derived neurotrophic factor and its role in the brain.
        Nature. 1997; 389: 856-860
        • Altar C.A.
        • DiStefano P.S.
        Neurotrophin trafficking by anterograde transport.
        Trends Neurosci. 1998; 21: 433-437
        • Austin M.C.
        • Whitehead R.E.
        • Edgar C.L.
        • Janosky J.E.
        • Lewis D.A.
        Localized decrease in serotonin transporter-immunoreactive axons in the prefrontal cortex of depressed subjects committing suicide.
        Neurosci. 2002; 114: 807-815
        • Benraiss A.
        • Chmielnicki E.
        • Lerner K.
        • Roh D.
        • Goldman S.A.
        Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain.
        J Neurosci. 2001; 21: 6718-6731
        • Biegon A.
        • Israeli M.
        Localization of the effects of electroconvulsive shock on beta- adrenoceptors in the rat brain.
        Eur J Pharmacol. 1986; 123: 329-334
        • Chen B.
        • Dowlatshahi D.
        • MacQueen G.M.
        • Wang H.J.
        • Young L.T.
        Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication.
        Biol Psychiatry. 2001; 50: 260-265
        • Croll S.D.
        • Suri C.
        • Compton D.L.
        • Simmons M.V.
        • Yancopoulos G.D.
        • Lindsay R.M.
        • et al.
        Brain-derived neurotrophic factor transgenic mice exhibit passive avoidance deficits, increased seizure severity and in vitro hyperexcitability in the hippocampus and entorhinal cortex.
        Neuroscience. 1999; 93: 1491-1506
        • Duman R.S.
        • Heninger G.R.
        • Nestler E.J.
        A molecular and cellular theory of depression.
        Arch Gen Psychiatry. 1997; 54: 597-606
        • Eaton M.J.
        • Staley J.K.
        • Globus M.Y.
        • Whittemore S.R.
        Developmental regulation of early serotonergic neuronal differentiation.
        Dev Biol. 1995; 170: 169-182
        • Fochtmann L.J.
        Animal studies of electrocunvulsive therapy.
        Psychopharmacol Bull. 1994; 30: 321-444
        • Isackson P.J.
        • Huntsman M.M.
        • Murray K.D.
        • Gall C.M.
        BDNF mRNA expression is increased in adult rat forebrain after limbic seizures.
        Neuron. 1991; 6: 937-948
        • Lindsay R.M.
        • Wiegand S.J.
        • Altar C.A.
        • DiStefano P.S.
        Neurotrophic factors.
        Trends Neurosci. 1994; 17: 182-190
        • Madsen T.M.
        • Treschow A.
        • Bengzon J.
        • Bolwig T.G.
        • Lindvall O.
        • Tingstrom A.
        Increased neurogenesis in a model of electroconvulsive therapy.
        Biol Psychiatry. 2000; 47: 1043-1049
        • Malberg J.E.
        • Eisch A.J.
        • Nestler E.J.
        • Duman R.S.
        Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus.
        J Neurosci. 2000; 20: 9104-9110
        • Mamounas L.A.
        • Altar C.A.
        • Blue M.A.
        • Kaplan D.R.
        • Tessarollo L.
        • Lyons W.E.
        BDNF promotes the regenerative sprouting, but not survival, of injured serotonergic axons in the adul rat brain.
        J Neurosci. 2000; 20: 771-782
        • Mamounas L.A.
        • Blue M.E.
        • Siuciak J.A.
        • Altar C.A.
        Brain-derived neurotrophic factor promotes the survival and sprouting of serotonergic axons in rat brain.
        J Neurosci. 1995; 15: 7929-7939
        • Martin-Iverson M.T.
        • Todd K.G.
        • Altar C.A.
        Brain-derived neurotrophic factor and neurotrophin-3 activate striatal dopamine and serotonin metabolism and related behaviors.
        J Neurosci. 1994; 14: 1262-1270
        • Nibuya M.
        • Morinobu S.
        • Duman R.S.
        Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments.
        J Neurosci. 1995; 15: 7539-7547
        • Nibuya M.
        • Nestler J.E.
        • Duman R.S.
        Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus.
        J Neurosci. 1996; 16: 2365-2372
        • Pencea V.
        • Bingaman K.D.
        • Wiegand S.J.
        • Luskin M.B.
        Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neurons in the parenchyma of the striatum, septum, thalamus, and hypothalamus.
        J Neurosci. 2001; 21: 6706-6717
        • Radka S.F.
        • Holst P.A.
        • Fritsche M.
        • Altar C.A.
        Presence of brain-derived neurotrophic factor in brain and human and rat but not mouse serum detected by a sensitive and specific immunoassay.
        Brain Res. 1996; 709: 122-301
        • Rocamora N.
        • Palacios J.M.
        • Mengod G.
        Limbic seizures induce a differential regulation of the expression of nerve growth factor, brain-derived neurotrophic factor and neurotrophin- 3, in the rat hippocampus.
        Brain Res Mol Brain Res. 1992; 13: 27-33
        • Shirayama Y.
        • Chen A.C.
        • Nakagawa S.
        • Russell D.S.
        • Duman R.S.
        Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression.
        J Neurosci. 2002; 22: 3251-3261
        • Siuciak J.A.
        • Boylan C.
        • Fritsche M.
        • Altar C.A.
        • Lindsay R.M.
        BDNF increases monoaminergic activity in rat brain following intracerebroventricular or intraparenchymal administration.
        Brain Res. 1996; 710: 11-20
        • Siuciak J.A.
        • Lewis D.R.
        • Wiegand S.J.
        • Lindsay R.M.
        Antidepressant-like effect of brain-derived neurotrophic factor (BDNF).
        Pharmacol Biochem Behav. 1997; 56: 131-137
        • Skolnick P.
        • Legutko B.
        • Li X.
        • Bymaster F.P.
        Current perspectives on the development of non-biogenic amine-based antidepressants.
        Pharmacol Res. 2001; 43: 411-423
        • Smith M.A.
        • Makino S.
        • Kvetnansky R.
        • Post R.M.
        Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus.
        J Neurosci. 1995; 15: 1768-1777
        • Smith M.A.
        • Zhang L.X.
        • Lyons W.E.
        • Mamounas L.A.
        Anterograde transport of endogenous brain-derived neurotrophic factor in hippocampal mossy fibers.
        Neuroreport. 1997; 8: 1829-1834
        • Stewart C.A.
        • Reid I.C.
        Repeated ECS and fluoxetine administration have equivalent effects on hippocampal synaptic plasticity.
        Psychopharmacology (Berl). 2000; 148: 217-223
        • Volpe B.T.
        • Wildmann J.
        • Altar C.A.
        BDNF prevents the loss of nigral neurons induced by excitotoxic striatal lesions.
        Neurosci. 1998; 83: 741-748
        • Zetterstrom T.S.
        • Pei Q.
        • Grahame-Smith D.G.
        Repeated electroconvulsive shock extends the duration of enhanced gene expression for BDNF in rat brain compared with a single administration.
        Brain Res Mol Brain Res. 1998; 57: 106-110