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

Author(s)

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

• Document type: Journal article
• Source: ACTA NEUROPSYCHIATRICA; v. N/A, p. 15-pg., 2022-09-14.

Abstract

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)

• FAPESP's process: 17/24304-0 - New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/19731-6 - Identification of epigenetic mechanisms induced by stress which modulate endocannabinoid signaling and neuroimmunological mechanisms as new therapeutic targets to treat the posttraumatic stress disorder (PTSD)
• Grantee: Sabrina Francesca de Souza Lisboa
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 19/04616-2 - Participation of P2X7-NLRP3 pathway in the modulation of behavioral, neurochemical and neuroplastic changes induced by stress
• Grantee: Letícia Vieira
• Support Opportunities: Scholarships in Brazil - Doctorate