Mecanismos gabaérgicos e opióides do núcleo parabraquial lateral envolvidos no controle da ingestão de sódio

• Ano de defesa: 2007
• Autor(a) principal: Oliveira, Lisandra Brandino de
• Orientador(a): Menani, José Vanderlei
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Carlos
• Programa de Pós-Graduação: Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas - PIPGCF
• País: BR
• Palavras-chave em Português: Neurofisiologia; Ingestão de sódio; Núcleo parabraquial lateral; GABA (Ácido Gama Aminobutírico); Opióide; Imunohistoquímica
• Área do conhecimento CNPq: CIENCIAS BIOLOGICAS::FISIOLOGIA
• Link de acesso: https://repositorio.ufscar.br/handle/ufscar/1197

The lateral parabrachial nucleus (LPBN) is a pontine structure located in the dorsal portion of the cerebelar superior peduncle. LPBN receives afferent projections from the area postrema (AP) and the medial portion of the nucleus of tractus solitarius (mNTS) and connects to prosencephalic areas related to hidroelectrolytic control, such as specific nuclei of the hypothalamus and amygdala. So, an important role of the LPBN could be integrating ascending information from AP and mNTS that could affect the activity of prosencephalic areas involved in the hidroelectrolytic control. Previous studies showed the presence of serotonergic, cholecystokininergic and α2-adrenergic mechanisms in the LPBN to control water and sodium intake. The γ-aminobutiric acid (GABA) is an inhibitory neurotransmitter present in the whole central nervous system and binding to two subtypes of receptors: GABAA and GABAB receptors. Previously, it was shown the participation of gabaergic mechanisms to control water, sodium and food intake. Gabaergic activation into the LPBN using bilateral injections of muscimol (GABAA receptor agonist) and baclofen (GABAB receptor agonist) induced a strong ingestion of sodium chloride (NaCl 0.3 M) in a short period of time (3 h) in satiated and normovolemic rats. Besides the presence of gabaergic mechanisms into the LPBN, it was already shown the presence of opioid receptors into the LPBN and the involvement of opioid mechanisms in the control of ingestive behavior. Therefore, the goals of this thesis were: a) to investigate the participation of GABAA and GABAB receptors on NaCl and water intake induced by gabaergic activation in the LPBN in satiated and sodium depleted rats; b) to study the effects of gabaergic activation into the LPBN on c-fos protein expression in satiated and sodium depleted rats, with or without access to NaCl 0.3 M; c) to test if acute lesion of the commissural NTS (cNTS area with the greatest c-fos protein expression in satiated rats not allowed to drink sodium or water and treated with muscimol and baclofen into the LPBN) and anteroventral 3o ventricle region (AV3V an important area involved in the hidroelectrolytic control) could affect the natriorexigenic and water intake induced by gabaergic activation into the LPBN in satiated rats; Abstract d) to study the effects of inhibition of α2-adrenergic and opioid mechanisms and activation of serotonergic mechanisms into the LPBN on NaCl and water intakeinduced by gabaergic activation in the same area in satiated rats; e) to investigate the participation of opioid mechanisms in the LPBN on sodium and water intake in satiated and sodium depleted rats; f) to verify the effects of gabaergic activation in the LPBN on arterial pressure and urinary excretion. Male Holtzman or Sprague Dawley rats with bilateral stainless steel guidecannulas implanted into the LPBN (volume of injection: 0.2 µl) were used. Other groups of rats, besides the cannulas implanted into the LPBN, they were also submitted to electrolytic lesion in the cNTS or AV3V region. In satiated rats, bilateral injections of muscimol (0.5 nmol) and baclofen (0.5 nmol) into the LPBN induced 0.3 M NaCl intake followed by an increase in water intake. The effects on sodium and water intake produced by muscimol injected into the LPBN were reduced by previous treatment with bicuculline (GABAA receptor antagonist - 1.6 nmol), but not CGP 35348 (GABAB receptor antagonist - 50 nmol). Pre treatment with bicuculline or CGP 35348 into the LPBN abolished the effects of baclofen on sodium and water intake. In 24 h sodium depleted rats (treatment with sc furosemide + sodium deficient diet and water for 24 h), muscimol and baclofen bilaterally injected into the LPBN, produced an early inhibition and a late facilitation of 0.3 M NaCl. Bicuculline, but not CGP 35348, abolished the inhibitory and facilitatory effects of muscimol injected into LPBN on sodium intake. In relation to sodium depleted rats treated with baclofen into the LPBN, CGP 35348 abolished the inhibitory effect, while bicuculline abolished the facilitatory effect of baclofen on sodium intake. These results suggest that the natriorexigenic effect in satiated rats and the dual effects on sodium intake in sodium depleted rats produced by muscimol injected into the LPBN depend on GABAA receptors activation. In relation to baclofen, in satiated rats the natriorexigenic effect of baclofen depends on activation of GABAA and GABAB receptors, but in sodium depleted rats, the early inhibition of sodium intake depends on GABAB receptors activation while the late facilitation depends on activation of GABAA receptors. Interestingly, although gabaergic activation promotes a facilitation of sodium intake, maybe there is not tonic gabaergic participation on sodium depletion-induced sodium intake, since inhibition of GABAA (bicuculline) and GABAB (CGP 35348) Abstract receptors into the LPBN did not affect 0.3 M NaCl and water intake in sodium depleted rats. Otherwise, in rats trained to drink 0.3 M NaCl only 2 h per day, CGP 35348, but not bicuculline, injected into the LPBN reduced 0.3 M NaCl, suggesting a tonic participation of GABAB, but not GABAA, receptors on sodium intake control in the protocol studied. (...)