Tolerance to repeated stress in rats with lesions of the serotoninergic neurons of the Median Raphe Nucleus and chronically treated with imipramine

Author(s)

Silva, K. ^[1] ; Carvalho, M. C. ^{[2, 3, 4]} ; Padovan, C. M. ^{[1, 2, 3]}

Affiliation

^[1] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Lab Neurobiol Estresse & Depressao, Ave Bandeirantes, 3900, Cidade Univ, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] INeC, Ave Bandeirantes 3900, BR-14049901 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Nucleo Pesquisa Neurobiol Emocoes NUPNE, Ave Bandeirantes, 3900, Cidade Univ, BR-14040900 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Lab Psicofarmacol, Ave Bandeirantes, 3900, Cidade Univ, BR-14040901 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Behavioural Brain Research; v. 302, p. 220-227, APR 1 2016.
• Web of Science Citations: 1

Abstract

Repeated exposure to aversive events leads to the development of tolerance to stress, which involves the serotonergic pathway originated in the Median Raphe Nucleus (MnRN) to the Dorsal Hippocampus (DH). However, it is not clear whether these lesion-induced deficits can be attenuated by treatment with antidepressants. Therefore, the aim of this work was to investigate the effects of chronic treatment with Imipramine (IMI) in rats with lesions in the MnRN and exposed to restraint stress. Male Wistar rats with or without neurochemical lesions of the MnRN serotonergic neurons with the neurotoxin 5,7-DHT were submitted to acute (2 h) or chronic restraint (2 h/day/seven consecutive days) and treated with saline (1 ml/kg) or imipramine (15 mg/kg) via intraperitoneal twice a day during the same period. In acutely restrained rats, stress occurred on the last day of treatment. Test in the elevated plus maze (EPM) was performed 24 h later. After EPM test, animals were sacrificed and had their brains removed. Dorsal hippocampus and striatum were dissected and the levels of 5-HT and 5-hydroxy-indoleacetic acid (5-HIAA) measured by HPLC analysis. Our results showed that in control rats exposure to acute restraint stress decreased exploration of the open and enclose arms of the EPM, an effect that was attenuated by imipramine. In rats with 5,7-DHT lesions, acute restraint did not change the exploration of the EPM, independently of the treatment. On the other hand, when chronically restrained, saline treated rat with 5,7-DHT lesion showed a reduced exploration of the open arms of the EPM. This effect was attenuated by simultaneous treatment with imipramine. HPLC analysis showed significantly decreases on 5-HT and 5-HIAA levels in the hippocampus, but not in the striatum. These later results confirm that 5,7-DHT lesions of the MnRN had significant impact on the serotonergic projections to the dorsal hippocampus which seems to be essential for the development of tolerance to repeated stress in the absence of any pharmacological treatment. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 09/11784-7 - Role of median raphe nucleus-dorsal hippocampus pathway in the antidepressant effects of treatment with imipramine in animals submitted to restraint stress
• Grantee: Kelly da Silva
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 07/07134-1 - Stress, serotonin, glutamate, and the median raphe nucleus-hippocampus pathway: behavioural and adult hippocampal neurogenesis studies
• Grantee: Claudia Maria Padovan
• Support Opportunities: Regular Research Grants