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Rapid and long-lasting antidepressant-like effects of ketamine and their relationship with the expression of brain enzymes, BDNF, and astrocytes
Viana, G S B; Vale, E M do; Araujo, A R A de; Coelho, N C; Andrade, S M; Costa, R O da; Aquino, P E A de; Sousa, C N S de; Medeiros, I S de; Vasconcelos, S M M de; Neves, K R T.
  • Viana, G S B; Universidade Federal do Ceará. Fortaleza. BR
  • Vale, E M do; Faculdade de Medicina Estácio de Juazeiro do Norte. Juazeiro do Norte. BR
  • Araujo, A R A de; Faculdade de Medicina Estácio de Juazeiro do Norte. Juazeiro do Norte. BR
  • Coelho, N C; Faculdade de Medicina Estácio de Juazeiro do Norte. Juazeiro do Norte. BR
  • Andrade, S M; Faculdade de Medicina Estácio de Juazeiro do Norte. Juazeiro do Norte. BR
  • Costa, R O da; Universidade Federal do Ceará. Fortaleza. BR
  • Aquino, P E A de; Universidade Federal do Ceará. Fortaleza. BR
  • Sousa, C N S de; Universidade Federal do Ceará. Fortaleza. BR
  • Medeiros, I S de; Universidade Federal do Ceará. Fortaleza. BR
  • Vasconcelos, S M M de; Universidade Federal do Ceará. Fortaleza. BR
  • Neves, K R T; Universidade Federal do Ceará. Fortaleza. BR
Braz. j. med. biol. res ; 54(2): e10107, 2021. graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1142578
ABSTRACT
Ketamine (KET) is an N-methyl-D-aspartate (NMDA) antagonist with rapid and long-lasting antidepressant effects, but how the drug shows its sustained effects is still a matter of controversy. The objectives were to evaluate the mechanisms for KET rapid (30 min) and long-lasting (15 and 30 days after) antidepressant effects in mice. A single dose of KET (2, 5, or 10 mg/kg, po) was administered to male Swiss mice and the forced swim test (FST) was performed 30 min, 15, or 30 days later. Imipramine (IMI, 30 mg/kg, ip), a tricyclic antidepressant drug, was used as reference. The mice were euthanized, separated into two time-point groups (D1, first day after KET injection; D30, 30 days later), and brain sections were processed for glycogen synthase kinase-3 (GSK-3), histone deacetylase (HDAC), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) immunohistochemical assays. KET (5 and 10 mg/kg) presented rapid and long-lasting antidepressant-like effects. As expected, the immunoreactivities for brain GSK-3 and HDAC decreased compared to control groups in all areas (striatum, DG, CA1, CA3, and mainly pre-frontal cortex, PFC) after KET injection. Increases in BDNF immunostaining were demonstrated in the PFC, DG, CA1, and CA3 areas at D1 and D30 time-points. GFAP immunoreactivity was also increased in the PFC and striatum at both time-points. In conclusion, KET changed brain BDNF and GFAP expressions 30 days after a single administration. Although neuroplasticity could be involved in the observed effects of KET, more studies are needed to explain the mechanisms for the drug's sustained antidepressant-like effects.
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Full text: Available Index: LILACS (Americas) Main subject: Brain / Brain-Derived Neurotrophic Factor / Ketamine / Antidepressive Agents Type of study: Prognostic study Limits: Animals Language: English Journal: Braz. j. med. biol. res Year: 2021 Type: Article Institution/Affiliation country: Faculdade de Medicina Estácio de Juazeiro do Norte/BR / Universidade Federal do Ceará/BR

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Full text: Available Index: LILACS (Americas) Main subject: Brain / Brain-Derived Neurotrophic Factor / Ketamine / Antidepressive Agents Type of study: Prognostic study Limits: Animals Language: English Journal: Braz. j. med. biol. res Year: 2021 Type: Article Institution/Affiliation country: Faculdade de Medicina Estácio de Juazeiro do Norte/BR / Universidade Federal do Ceará/BR