Decreased sensitivity to antidepressant drugs in Wistar Hannover rats submitted to two animal models of depression

Autor(es)

Silveira, Kennia M. M. ; Sartim, Ariandra G. G. ; Vieira, Leticia ; Lisboa, Sabrina F. F. ; Wegener, Gregers ; Joca, Samia R. L.

• Tipo de documento: Artigo Científico
• Fonte: ACTA NEUROPSYCHIATRICA; v. N/A, p. 15-pg., 2022-09-14.

Resumo

The Wistar Hannover rat (WHR) is a strain commonly used for toxicity studies but rarely used in studies investigating depression neurobiology. In this study, we aimed to characterise the behavioural responses of WHR to acute and repeated antidepressant treatments upon exposure to the forced swim test (FST) or learned helplessness (LH) test. WHR were subjected to forced swimming pre-test and test with antidepressant administration (imipramine, fluoxetine, or escitalopram) at 0, 5 h and 23 h after pre-test. WHR displayed high immobility in the test compared to unstressed controls (no pre-swim) and failed to respond to the antidepressants tested. The effect of acute and repeated treatment (imipramine, fluoxetine, escitalopram or s-ketamine) was then tested in animals not previously exposed to pre-test. Only imipramine (20 mg/kg, 7 days) and s-ketamine (acute) reduced the immobility time in the test. To further investigate the possibility that the WHR were less responsive to selective serotonin reuptake inhibitors, the effect of repeated treatment with fluoxetine (20 mg/kg, 7 days) was investigated in the LH model. The results demonstrated that fluoxetine failed to reduce the number of escape failures in two different protocols. These data suggest that the WHR do not respond to the conventional antidepressant treatment in the FST or the LH. Only s-ketamine and repeated imipramine were effective in WHR in a modified FST protocol. Altogether, these results indicate that WHR may be an interesting tool to investigate the mechanisms associated with the resistance to antidepressant drugs and identify more effective treatments. (AU)

• Processo FAPESP: 17/24304-0 - Novas perspectivas no emprego de fármacos que modificam neurotransmissores atípicos no tratamento de transtornos neuropsiquiátricos
• Beneficiário: Francisco Silveira Guimaraes
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/19731-6 - Identificação de mecanismos epigenéticos induzidos por estresse que modulam a sinalização endocanabinóide e a resposta neuroimunológica como novos alvos farmacológicos no tratamento do transtorno de estresse pós-traumático (PTSD)
• Beneficiário: Sabrina Francesca de Souza Lisboa
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 19/04616-2 - Participação da via P2X7-NLRP3 na modulação de alterações comportamentais, neuroquímicas e neuroplás
• Beneficiário: Letícia Vieira
• Modalidade de apoio: Bolsas no Brasil - Doutorado