Reversal of corticosterone-induced BDNF alterations by the natural antioxidant alpha-lipoic acid alone and combined with desvenlafaxine: Emphasis on the neurotrophic hypothesis of depression.
Brain derived neurotrophic factor (BDNF) is linked to the pathophysiology of depression. We hypothesized that BDNF is one of the neurobiological pathways related to the augmentation effect of alpha-lipoic acid (ALA) when associated with antidepressants. Female mice were administered vehicle or CORT 20mg/kg during 14 days. From the 15th to 21st days the animals were divided in groups that were further administered: vehicle, desvenlafaxine (DVS) 10 or 20mg/kg, ALA 100 or 200mg/kg or the combinations of DVS10+ALA100, DVS20+ALA100, DVS10+ALA200 or DVS20+ALA200. ALA or DVS alone or in combination reversed CORT-induced increase in immobility time in the forced swimming test and decrease in sucrose preference, presenting, thus, an antidepressant-like effect. DVS10 alone reversed CORT-induced decrease in BDNF in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST). The same was observed in the HC and ST of ALA200 treated animals. The combination of DVS and ALA200 reversed CORT-induced alterations in BDNF and even, in some cases, increased the levels of this neurotrophin when compared to vehicle-treated animals in HC and ST. Taken together, these results suggest that the combination of the DVS+ALA may be valuable for treating conditions in which BDNF levels are decreased, such as depression.
Neuropsychopharmacology Laboratory, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address: carensoarez@yahoo.com.br.
Caren Nádia Soares
CN
de Sousa
Neuropsychopharmacology Laboratory, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address: lucasmeneses07@gmail.com.
Lucas Nascimento
LN
Meneses
Neuropsychopharmacology Laboratory, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address: germana_vasconcelos@yahoo.com.br.
Germana Silva
GS
Vasconcelos
Neuropsychopharmacology Laboratory, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address: marciacalheiros@yahoo.com.br.
Márcia Calheiros Chaves
MC
Silva
Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address: jessicacalheiros@hotmail.com.
Jéssica Calheiros
JC
da Silva
Neuropsychopharmacology Laboratory, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address: daniellesilmacedo@gmail.com.
Danielle
D
Macêdo
Neuropsychopharmacology Laboratory, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address: daviddelucena@me.com.
David Freitas
DF
de Lucena
Neuropsychopharmacology Laboratory, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address: silvania@pq.cnpq.br.
Silvânia Maria Mendes
SM
Vasconcelos
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage; D000975:Antioxidants / Q000008:administration & dosage*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003345:Corticosterone / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D000069468:Desvenlafaxine Succinate / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D013550:Swimming / Q000502:physiology / Q000523:psychology; D008063:Thioctic Acid / Q000008:administration & dosage*
D000928:Antidepressive Agents; D000975:Antioxidants; D019208:Brain-Derived Neurotrophic Factor; D008063:Thioctic Acid; D003345:Corticosterone; D000069468:Desvenlafaxine Succinate
Alpha-lipoic acid; BDNF; Corticosterone model of depression; Desvenlafaxine; Major depressive disorder; Treatment resistant depressive disorder