The Dorsomedial Hypothalamus Is Involved in the Mediation of Autonomic and Neuroendocrine Responses to Restraint Stress

Abstract

We hypothesized that dorsomedial hypothalamus (DMH) modulates autonomic and neuroendocrine responses in rats at rest and when subjected to restraint stress (RS). Male Wistar rats were used, and guide cannulas were bilaterally implanted in the DMH for microinjection of vehicle or the nonspecific synaptic blocker CoCl 2 (1 mM/100 nl). A polyethylene catheter was inserted into the femoral artery for the recording of arterial pressure and heart rate (HR). Tail temperature was measured using a thermal camera. The session of RS started 10 min after DMH treatment with vehicle or CoCl2. Under homecage condition, the pretreatment of DMH with CoCl 2 increased baseline blood pressure (BP), and heart rate (HR) without affecting the tail temperature. In addition, it decreased plasma vasopressin levels without affecting plasma corticosterone and oxytocin contents. When rats pretreated with CoCl 2 were exposed to RS, the RS-evoked cardiovascular were similar to those observed in vehicle-treated animals; however, because cobalt pretreatment of the DMH increased baseline BP and HR values, and the RS-evoked cardiovascular responses did not exceed those observed in vehicle-treated animals, suggesting a possible celling limit, the possibility that DMH is involved in the modulation of RS-evoked cardiovascular responses cannot be certainly excluded. Nonetheless, the pretreatment of DMH with CoCl 2 blocked the reduction in tail temperature caused by RS. The DMH pretreatment with CoCl 2 did not modify the RS-evoked increase in plasma corticosterone and oxytocin contents. In conclusion, the present data suggest the involvement of DMH in the maintenance of BP, HR, and vasopressin release under the rest conditions at the home-cage. Furthermore, indicate that DMH is an important thermoregulatory center during exposure to RS, regulating tail artery vasoconstriction.

Dynamics in brain activation and behaviour in acute and repeated social defensive motivated behaviour

“…The behavioural response to an aversive context is accompanied by neuroendocrine and autonomic responses. The mobilization of paraventricular and dorsomedial nuclei of the hypothalamus (PVH and DMH), both during the first and third exposure, as well during restraint stress, agrees with their role in neuroendocrine and autonomic responses to stressors 14,[75][76][77][78] .…”

“…The increase in DMH activity is also related to an increase in cardiac frequency, which is common in aversive situations, including social defeat and restraint stress 78,[80][81][82] .…”

“…We quantified the density of Fos-labeled cells in 31 brain regions that followed the Allen Mouse Brain Atlas and The Mouse Brain in Stereotaxic Coordinates 91,92 . In the hypothalamus, we analysed nuclei involved with the response to conspecifics, namely, the medial preoptic nucleus (MPN), the ventrolateral part of the ventromedial nucleus (rostral and dorsal portion) (rVMHvl and cVMHvl), tuberal nucleus (TU) and the ventral premammillary nucleus (PMV) 9,21,28,39,58 ; the dorsal premammillary nucleus (PMD), that is involved with information integration of threats cues 9,15,45,59 ; nuclei related with the neuroendocrine and autonomic response to stressors, such as paraventricular nucleus (both parvicellular and magnocellular parts) (PVHparv and PVHmag) and dorsomedial nucleus of the hypothalamus (rostral and caudal portion) (DMHa and DMHc) 27,76,78,93 ; and the juxtaparaventricular, juxtadorsomedial, juxtraventromedial (dorsal and ventral portion) and subfornical regions of the lateral hypothalamus (LHAjp, LHAjd, LHAjvd, LHAjvv and LHAsf), which are related with the integration between the septo-hippocampal system and defensive behaviour system components 45,59,69,94 . Furthermore, we also analysed regions involved with the processing of social and contextual cues as the medial amygdala (anteroventral, anterodorsal, posteroventral and posterodorsal portion) (MeAav, MeAad, MeApv and MeApd), bed nuclei of stria terminalis (principal and transversal/interfascicular portion) (BSTpr and BSTtr,if) and lateral septum (caudodorsal and rostroventral part) (LSc and LSr) 17,95,96 .…”

Differential Level of RXFP3 Expression in Dopaminergic Neurons Within the Arcuate Nucleus, Dorsomedial Hypothalamus and Ventral Tegmental Area of RXFP3-Cre/tdTomato Mice

“…The functional relevance of this co-expression is currently unknown, especially since the role of DMH dopaminergic neurons remains largely unexplored. However, the DMH is considered to be a relay station for multiple feeding, neuroendocrine and stress pathways, as it receives multiple inputs from the majority of hypothalamic regions including the ARC ( Pirník et al, 2018 ), and has complex outputs to autonomic and other pathways ( Brasil et al, 2020 ). Notably, it contains a range of anorexigenic neuron populations that may express RXFP3, including cholinergic and proopiomelanocortin (POMC) neurons.…”

Envolvimento do sistema renina-angiotensina na modulação das respostas autonômicas, neuroendócrina e funcionais ocasionadas pela exposição aguda ao estresse de restrição em ratos

“…Esse resultado, possivelmente, deve-se ao metabolismo hepático dos fármacos administrados, e não seja decorrência do estímulo estressor, uma vez que não observamos diferença entre o grupo estressado e tratado com veículo e o grupo naïve (não estressado). Outra resposta bem consolidada frente à exposição ao ER é a ativação do eixo HPA com consequente liberação de corticosterona (BRASIL et al, 2020;BUSNARDO et al, 2019;LOPES-AZEVEDO et al, 2019). Assim sendo, avaliamos a participação do SRA na resposta neuroendócrina ocasionada pelo ER agudo de 180 min, através da determinação das concentrações plasmáticas de corticosterona em animais pré-tratados com veículo, losartan (1 mg/kg) ou lisinopril (0,3 mg/kg), imediatamente após o término do ER.…”