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Master's Dissertation
DOI
10.11606/D.60.2013.tde-21062013-140940
Document
Author
Full name
Ariandra Guerini Sartim
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2013
Supervisor
Committee
Joca, Sâmia Regiane Lourenço (President)
Souza, Gloria Emilia Petto de
Moreira, Fabrício de Araújo
Title in Portuguese
Efeitos da administração de canabidiol no CPFmv de ratos submetidos ao teste do nado forçado
Keywords in Portuguese
canabidiol
córtex pré-frontal medial ventral
depressão
Abstract in Portuguese
A administração sistêmica de canabidiol (CBD), o principal constituinte não psicomimético da Cannabis sativa, induz efeito antidepressivo em modelos préclínicos. O mecanismo de ação do canabidiol, no entanto, permanece pouco conhecido, podendo envolver a ativação de receptores serotoninérgicos do tipo 1A (5-HT1A). Ademais, as estruturas encefálicas envolvidas nesses efeitos permanecem desconhecidas. O córtex pré-frontal medial ventral (CPFmv), dividido em infra-límbico (IL) e pré-límbico (PL), recebe densa inervação serotoninérgica e desempenha importante papel na modulação da resposta emocional ao estresse e na neurobiologia da depressão. Dessa forma, o objetivo do presente trabalho foi avaliar a hipótese de que a administração de canabidiol no CPFmv, diferenciado em PL e IL, produz efeito tipo-antidepressivo por meio da ativação de receptores 5- HT1A. Para tanto, ratos Wistar canulados bilateralmente no CPFmv, receberam CBD (10, 30, 60 nmol/0,2?l) ou veículo intra-PL e CBD (30, 45 e 60nmol/0,2?l) ou veículo intra-IL e foram submetidos ao teste do nado forçado ou ao teste do campo aberto. Outro grupo de animais recebeu microinjeção (intra PL ou IL) do agonista de receptores 5-HT1A, 8-OH-DPAT (5, 10nmol/0,2?l) e foram submetidos aos mesmos testes. Um grupo adicional recebeu um antagonista 5-HT1A, WAY1006365 (10, 30nmol/0,2?l), seguido pela administração de 8-OH-DPAT (10nmol0,2?l) ou CBD (10 nmol0,2?l) intra-PL, ou 8-OH-DPAT (10nmol0,2?l) ou CBD (45 nmol0,2?l) intra-IL, e avaliados no teste do nado forçado. Os resultados demonstraram que a administração de CBD e de 8-OH-DPAT, intra-PL e intra-IL, reduziu significativamente o tempo de imobilidade no teste do nado forçado, um efeito tipoantidepressivo, sem alterar a atividade locomotora dos animais no teste do campo aberto. Além disso, a administração de WAY100635 intra-PL e intra-IL não alterou o tempo de imobilidade per se, mas foi capaz de bloquear os efeitos da administração do CBD e do 8-OH-DPAT. Esses resultados sugerem que a administração local do CBD no CPFmv induz efeito tipo-antidepressivo por meio da ativação de receptores 5-HT1A. Portanto, é possível que o CPFmv esteja envolvido no efeito tipoantidepressivo induzido pelo CBD.
Title in English
Effects of cannabidiol administration into the vmPFC of rats submitted to the forced swimming test
Keywords in English
cannabidiol
depression
ventromedial prefrontal córtex
Abstract in English
Systemic administration of cannabidiol (CBD), the main non-psychotomimetic constituent of Cannabis sativa, induces antidepressant-like effects in pre-clinical models. The mechanism of action of Cannabidiol, which remains poorly understood, may involve serotonergic type 1A receptors activation (5-HT1A). Furthermore, the brain structures involved in these effects are still unknown. The ventral medial prefrontal cortex (vmPFC), divided in infra-limbic (IL) and pre-limbic (PL) subregions, receives dense serotonergic innervation and plays an important role in the modulation of emotional responses to stress and in the neurobiology of depression. Thus, the aim of this study was evaluate the hypothesis that the administration of cannabidiol into the vmPFC, differentiated into IL and PL, would induce antidepressant-like effect by activating 5-HT1A receptors. Therefore, male Wistar rats with cannulae bilaterally implanted into the Il and PL were given CBD (10, 30, 45, 60 nmol/0,2?l) or vehicle and were submitted to the forced swimming test or to the open field test. Another group of animals received microinjections (intra PL or IL) of the 5- HT1A agonist 8-OH-DPAT (5, 10nmol/0,2?l) and was submitted to the same tests. An additional group received an 5-HT1A antagonist, WAY100635 (10, 30 nmol/0,2?l.), followed by the administration of 8-OH-DPAT (10 nmol/0,2?l) or CBD (10 nmol0,2?l) intra-PL, or 8-OH-DPAT (10nmol0,2?l) or CBD (45 nmol0,2?l) intra- IL, and avaluated in the forced swimming test. The results showed that CBD and 8- OH-DPAT administration, intra-PL and intra-IL, significantly reduced the immobility time in the forced swimming test, an antidepressant-like effect, without changing the locomotor activity of the animals in the open field test. Moreover, the administration of WAY100635, intra-PL and intra-IL, did not change the immobility time per se, but blocked the CBD- and 8-OH-DPAT-induced effects. These results suggest that the local administration of CBD into the vmPFC induces antidepressant-like effects through the activation of 5-HT1A receptors. Therefore, it is possible that the vmPFC is involved in CBD-induced antidepressant-like effect.
 
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Publishing Date
2013-07-02
 
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