Prelimbic medial prefrontal cortex disruption during adolescence increases susceptibility to helpless behavior in adult

Autor(es)

Uliana, Daniela L. ^[1] ; Gomes, V, Felipe ; Grace, Anthony A. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Pittsburgh, Dept Neurosci Psychiat & Psychol, A210 Langley Hall, Pittsburgh, PA 15260 - USA

^[2] Gomes, Felipe, V, Univ Pittsburgh, Dept Neurosci Psychiat & Psychol, A210 Langley Hall, Pittsburgh, PA 15260 - USA

• Tipo de documento: Artigo Científico
• Fonte: European Neuropsychopharmacology; v. 35, p. 111-125, JUN 2020.
• Citações Web of Science: 0

Resumo

Major depressive disorder (MDD) is a disabling mental disorder worldwide. Several animal models have been used to study the neurobiology of this disorder, including the learned helplessness (LH) paradigm, in which susceptible animals show helpless behavior indicated by fails to escape a controllable footshock. This behavior has been associated with a downregulation of ventral tegmental area (VTA) dopamine (DA) system activity. The prelimbic portion of the prefrontal cortex (plPFC) plays an important role in the modulation of helpless behavior, but so far there is no evidence indicating that its developmental disruption alters susceptibility to helpless behavior. We investigated the impact of plPFC lesion performed at adolescence (postnatal day 31-33) or adulthood (postnatal day 70-72) on anxiety responses (elevated plus-maze), susceptibility to helpless behavior, and the VTA DA system activity in adult Sprague-Dawley rats. Whereas adult plPFC lesions induced neither anxiety responses nor increased susceptibility to helpless behavior (plPFC lesion: 33.3% of helplessness; controls: 30.8% of helplessness rats), adolescent plPFC lesions induced anxiety responses and increased the proportion of rats showing helpless at adulthood (plPFC lesion: 92.3% helplessness; controls: 42.1% helplessness rats). Moreover, only helpless rats in the groups showed a decreased VTA DA system population activity that was confined to the medial portion of the VTA. These findings suggest that the impairment of plPFC activity during adolescence occurs during a critical window for the development of helpless behavior in adult rats, indicating that predisposition or early life adverse events that impair plPFC activity may enhance susceptibility to depression in adulthood. (C) 2020 Elsevier B.V. and ECNP. All rights reserved. (AU)

• Processo FAPESP: 18/17597-3 - O impacto do estresse sobre o sistema dopaminérgico é determinado pelo período crítico de plasticidade: implicações para a depressão e a esquizofrenia e o estudo de novos alvos farmacológicos
• Beneficiário: Felipe Villela Gomes
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores