Cardiovascular effects of noradrenaline microinjection in the bed nucleus of the stria terminalis of the rat brain

Abstract

The bed nucleus of the stria terminalis (BST) is a limbic structure involved in regulating the hypothalamic-pituitary-adrenal axis as well as in central cardiovascular control. We report here on cardiovascular effects caused by microinjection of noradrenaline (NA) in the BST of the rat brain and the peripheral mechanisms involved in their mediation. Injection of NA (3, 7, 10, 15, 30, or 45 nmol in 100 nl) in the BST of unanesthetized rats caused long-lasting dose-related pressor and bradycardiac responses. No responses were observed when the dose of 10 nmol NA was microinjected into surrounding structures, such as the anterior commissure, the stria terminalis, the fornix, and the internal capsule, indicating a predominant action at the BST. Additionally, microinjection of 50 nmol tyramine, an indirectly acting sympathomimetic amine, caused similar pressor response, indicating local NA release in the BST. Responses to NA microinjection in the BST were markedly reduced in urethane-anesthetized rats, favoring the idea of a central action without significant leakage to the peripheral circulation. The pressor response was potentiated by i.v. pretreatment with the ganglion blocker pentolinium and blocked by i.v. pretreatment with the selective V(1)-vasopressin antagonist dTyr(CH(2))(5)(Me)AVP, suggesting its mediation by vasopressin release into circulation. The bradycardiac response to NA microinjected into the BST was also abolished by pretreatment with the vasopressin antagonist, indicating its reflex origin. In conclusion, results indicate that microinjection of NA into the BST evokes pressor responses, which are mediated by acute vasopressin release.

Brain Pathways Involved in the Modulatory Effects of Noradrenaline in Lateral Septal Area on Cardiovascular Responses

“…PVN paraventricular nucleus of hypothalamus, BNST bed nucleus of stria terminalis, dmPAG dorsomedial periaqueductal gray, PL and IL prelimbic and infralimbic prefrontal cortex, MeA medial amygdaloid nucleus, DBB diagonal band of Broca, dlPAG dorsolateral periaqueductal gray, and Cg1 cingulate cortex area 1 * Different from vehicle-treated group (aCSF) group, P \ 0.0001 # Different from NA-treated (NA) group, P \ 0.0001 structures are activated after administration of NA into the LSA. All these structures are able to cause vasopressin release to periphery after stimulation Crestani et al 2007;Fernandes et al 2003;Fortaleza et al 2011;Pelosi and Correa 2005). In contrast, no changes in the pattern of c-Fos expression were found in the diagonal band of Broca (DBB), cingulate cortex 1 (Cg1), and dorsolateral periaqueductal gray (dlPAG).…”

Neural Pathways Underlying Lactate-Induced Panic

“…The c-Fos induction in the rostral BNST region correlated strongly with anxietylike responses, whereas c-Fos induction in the caudal BNST correlated with panic-like cardiovascular responses. Although other studies have demonstrated that the BNST regulates anxiety-like behavior (Sajdyk et al, 2007) and autonomic activity (Crestani et al, 2007), the BNST's role may depend on the context. In the present article, a subsequent experiment (ie experiment 3) demonstrated that inactivation of the rostro-caudal BNST region (see Figure 4) with acute muscimol injections selectively blocked the anxiogenic effects of the lactate + L-AG infusions without affecting the cardiorespiratory activation, providing strong support for the hypothesis that the BNST selectively regulates anxiety behavior, but not panic-like cardiorespiratory responses in the panic model presented here (see Figure 5a for a hypothetical model).…”

Função da neurotransmissão noradrenérgica do núcleo medial da amígdala na modulação do sistema cardiovascular em ratos

“…O pentolínio causou potencialização semelhante em respostas pressoras causadas pela microinjeção de NA em outras regiões do cérebro, sugerindo o envolvimento de uma mediação humoral. Outros estudos do nosso grupo mostraram que o aumento da pressão arterial e queda na frequência cardíaca causado pela microinjeção de NA em diversas regiões do cérebro foi mediado por liberação de vasopressina (CORREA et al, 1985;FERNANDES et al, 2003;PELOSI e CORREA, 2005;SCOPINHO et al, 2006;CRESTANI et al, 2007;PELOSI et al, 2008;BUSNARDO et al, 2009a).…”

“…Além disso, existe uma via indireta da amígdala para o núcleo leito da estria terminal (NLET) e da área pré-óptica que conecta-se com a amígdala para o núcleo paraventricular (SAWCHENKO e SWANSON, 1983;MCDONALD, 1988). O NLET é um componente heterogêneo funcional da amígdala estendida que tem sido implicado na modulação das respostas cardiovasculares (CRESTANI et al, 2007). Administração de NA no NLET causa resposta pressora e bradicardia que dependem da liberação de vasopressina pelo NPV (CRESTANI, BUSNARDO et al, 2009).…”

“…Foram observadas respostas cardiovasculares após a microinjeção de NA em regiões do cérebro envolvidas na modulação do sistema cardiovascular, tais como o núcleo do trato solitário (NTS) (VLAHAKOS et al, 1985), o córtex pré-frontal medial (CPFM) (FERNANDES et al, 2003), a área septal lateral (ASL) (SCOPINHO et al, 2006), o núcleo leito da estria terminal (NLET) (CRESTANI et al, 2007) e a amígdala (OHTA et al, 1991 (LAM et al, 1995;KAEHLER et al, 2000;KNUEPFER et al, 2001;MULLER et al, 2001; VAN DEN BUUSE et al, 2001;KAPUSTA et al, 2002;KUBO et al, 2002). Em particular, o estresse por restrição (ER) é um modelo experimental que gera um estímulo aversivo inescapável.…”