Antidepressant-Like Effect of Brain-derived Neurotrophic Factor (BDNF)

doi:10.1016/S0091-3057(96)00169-4

Pharmacology Biochemistry and Behavior

Volume 56, Issue 1, January 1997, Pages 131-137

https://doi.org/10.1016/S0091-3057(96)00169-4 Get rights and content

Abstract

Previous studies have shown that infusion of brain-derived neurotrophic factor (BDNF) into the midbrain, near the PAG and dorsal/median raphe nuclei, produced analgesia and increased activity in monoaminergic systems. Alterations in monoaminergic activity have also been implicated in the pathogenesis and treatment of depression. The present studies examined the ability of centrally administered BDNF to produce antidepressant-like activity in two animal models of depression, learned helplessness following exposure to inescapable shock and the forced swim test. In the learned helplessness paradigm, vehicle-infused rats pre-exposed to inescapable shock (veh/shock) showed severe impairments in escape behavior during subsequent conditioned avoidance trials, including a 47% decrease in the number of escapes and a 5 fold increase in escape latency, as compared to vehicle-infused rats which received no pre-shock treatment (veh/no shock). Midbrain BDNF infusion (12–24 μg/day) reversed these deficits, and in fact, BDNF-infused rats pre-exposed to inescapable shock (BDNF/shock) showed escape latencies similar to veh/no shock and BDNF/no shock rats. In the forced swim test, BDNF infusion decreased the immobility time by 70% as compared to vehicle-infused controls. Non-specific increases in activity could not account for these effects since general locomotor activity of BDNF- and vehicle-infused animals was not different. These findings demonstrate an antidepressant-like property of BDNF in two animal models of depression, which may be mediated by increased activity in monoaminergic systems.

Section snippets

Animal Surgery

Male Sprague–Dawley rats were housed and treated in compliance with AALAC and NIH guidelines. All animal experiments were conducted according to protocols approved by the Institutional Animal Care and Use Committee at Regeneron. Rats were maintained on a 12:12 light/dark cycle and allowed food and water ad lib. Surgery was performed as previously described 48, 49, 50. Briefly, animals were anesthetized with chloropent (149 mg/kg chloral hydrate and 30.8 mg/kg sodium pentobarbital, IP) and

Learned Helplessness

Fig. 1A summarizes the effect of learned helplessness induction on the number of escapes made during conditioned avoidance testing in vehicle- and BDNF-infused rats. A 2-way ANOVA indicated an overall effect of BDNF administration [veh vs. BDNF, F(2, 86) = 16.8, p < 0.0001) and of shock pretreatment (shock vs. no shock, F(1, 86) = 19.3, p < 0.0001). The two-way ANOVA also indicated a significant interaction between infusion and shock treatment (F(2, 86) = 14.4, p < 0.0001), such that veh/shock

Discussion

The present studies demonstrate that administration of BDNF produces an antidepressant-like effect in two animals models of depression. In the learned helplessness paradigm, vehicle-infused rats subjected to inescapable electric foot-shocks showed escape deficits, i.e., decreased number of escapes and increased latency to escape, when subsequently tested in a conditioned avoidance paradigm. These escape deficits were reversed by chronic administration of BDNF. In the forced swim test, midbrain

Nomenclature

BDNF, brain-derived neurotrophic factor; PAG/DR, periaqueductal gray/dorsal raphe; VEH, vehicle-infused; 5HT, serotonin; 5HIAA, 5-hydroxyindole acetic acid.

Acknowledgements

The authors would like to thank Dr. Mary Ann Pelleymounter for her helpful comments regarding these studies. Portions of this work were presented at the XIX C.I.N.P. Congress, Washington, DC, July, 1994 and the Society for Neuroscience Meeting, Miami, FL, November, 1994.

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ArticlesAntidepressant-Like Effect of Brain-derived Neurotrophic Factor (BDNF)

Abstract

Section snippets

Animal Surgery

Learned Helplessness

Discussion

Nomenclature

Acknowledgements

Pharmacol. Biochem. Behav.

Biochem. Behav.

Eur. J. Pharmacol.

Neurosci.

Prog. Neuropsychopharmacol. Biol. Psychiat.

Exp. Neurol.

Pharmacol. Biochem. Behav.

Eur. J. Pharmacol.

Brain Res.

Behav. Neural Biol.

Behav. Neural Biol.

Pharmacol. Biochem. Behav.

Brain Res.

Brain Res.

Prog. Neuropsychopharmacol. Biol. Psychiatry

Pharmacol. Ther.

Physiol. Behav.

J. Psychiatr. Res.

Brian Res.

Brian Res.

Brian Res.

Brain-derived neurotrophic factor augments rotational behavior and nigrostriatal dopamine turnover in vivo

Proc. Natl. Acad. Sci. USA

Neurobiological correlates of depression and anxiety in normal individuals

Biochemical hypotheses of mood and anxiety disorders

The serotonin hypothesisNecessary but not sufficient

Dopamine and depression

J. Neural Trans.

Norepinephrine in depressive reactions

Arch. Gen. Psychiatry

Neuropeptide regulation by BDNF and NGF in adult rat forebrain

Eur. J. Neurosci.

Influence of naloxone on antidepressant drug effects in the forced swimming test

Psychopharmacol.

Endorphins in psychiatry

Psychiat. Dev.

Alteration in GABA metabolism and met-enkephalin content in rat brain following repeated electroconvulsive shock therapy

J. Neurochem.

Structure and function of the brain serotonergic system

Physiol. Rev.

Articles
Antidepressant-Like Effect of Brain-derived Neurotrophic Factor (BDNF)