Rewarding and Antidepressant Properties of Ketamine and Ethanol: Effects on the Brain-Derived Neurotrophic Factor and TrkB and p75(NTR) Receptors

Autor(es)

Conto, Marcos Brandao ; Pautassi, Ricardo Marcos ; Camarini, Rosana

• Tipo de documento: Artigo Científico
• Fonte: Neuroscience; v. 493, p. 14-pg., 2022-06-15.

Resumo

There is a high level of comorbidity between depression and alcohol use disorder. Subanesthetic doses of ketamine induce short-acting and enduring antidepressant effects after a single or a few administrations. Considering such comorbidity, we assessed, in Swiss male mice, if ketamine-induced antidepressant-like effects would alter ethanol's rewarding effects; and, if ethanol pretreatment would alter the rewarding and antidepressant effects of ketamine. The role of the brain-derived neurotrophic factor (BDNF) and its high and low affinity receptors TrkB and p75NTR, respectively, in both reward and depression-related behaviors is well established. The present study assessed, in outbred Swiss male mice, the expression of these proteins in the prefrontal cortex and hippocampus. Ketamine did not alter the development of ethanol-induced conditioned place preference (CPP), yet ethanol inhibited the expression of CPP induced by 50 mg/kg ketamine. The antidepressant action of 50 mg/kg ketamine was attenuated after repeated treatment (i.e., developed tolerance), an effect blocked by ethanol preexposure; ethanol also inhibited the antidepressant effect of 30 mg/kg ketamine. Ketamine (50 mg/kg) and Ethanol-Ketamine (50 mg/kg) groups showed lower levels of 145 kDa TrkB in the hippocampus than Saline treated group. Ethanol-Ketamine (50 mg/kg) decreased the hippocampal expression of p75NTR compared to Saline-Saline and Saline-Ethanol groups. Ketamine (50 mg/kg) induced hippocampal downregulation of 145 kDa TrkB may contribute to ketamine-induced antidepressant tolerance. Likewise, a relationship between low hippocampal levels of p75NTR in the Ethanol-Ketamine (50 mg/kg) and ketamine-induced CPP blockade may be considered. The findings underscore potential ethanol-ketamine interactions likely to undermine ketamine putative antidepressant effects. (C) 2022 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 12/09898-7 - Efeitos de diferentes formas de estimulação ambiental sobre as alterações comportamentais induzidas pelo etanol: Envolvimento de modificações epigenéticas e de fatores neurotróficos e de transcrição
• Beneficiário: Marcos Brandão Contó
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/05038-0 - Efeito do enriquecimento ambiental sobre a resiliência ao estresse crônico imprevisível: regulação epigenética do gene BDNF e consequências sobre o consumo de etanol
• Beneficiário: Rosana Camarini
• Modalidade de apoio: Auxílio à Pesquisa - Regular