Department of Physiological Sciences, Center of Biological Sciences - CCB, Federal University of Santa Catarina (UFSC), 88040-970, Florianópolis, SC, Brazil.
Department of Physiology & Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-900, São Paulo, SP, Brazil.
Neuropharmacology. 2021 Jan;182:108397. doi: 10.1016/j.neuropharm.2020.108397. Epub 2020 Nov 11.
The present study aimed to evaluate the effects of pharmacological manipulation of α-adrenergic agonists in the dorsal raphe nucleus (DR) on food intake in satiated rats. Adult male Wistar rats with chronically implanted cannula in the DR were injected with adrenaline (AD) or noradrenaline (NA) (both at doses of 6, 20 and 60 nmol), or α-1 adrenergic agonist phenylephrine (PHE) or α-2 adrenergic agonist clonidine (CLO) (both at doses of 6 and 20 nmol). The injections were followed by the evaluation of ingestive behaviors. Food and water intake were evaluated for 60 min. Administration of AD and NA at 60 nmol and CLO at 20 nmol increased food intake and decreased latency to start consumption in satiated rats. The ingestive behavior was not significantly affected by PHE treatment in the DR. CLO treatment increased Fos expression in the arcuate nucleus (ARC) and paraventricular nucleus of the hypothalamus (PVN) in rats that were allowed to eat during the experimental recording (AF group). However, when food was not offered during the experiment (WAF group), PVN neurons were not activated, whereas, neuronal activity remained high in the ARC when compared to control group. Noteworthy, ARC POMC neurons expressed Fos in the AF group. However, double-labeled POMC/Fos cells were absent in the ARC of the WAF group, although an increase in Fos expression was observed in non-POMC cells after CLO injections in the WAF group. In conclusion, the data from the present study highlight that the pharmacological activation of DR α-adrenoceptors affects food intake in satiated rats. The feeding response evoked by CLO injections into DR was similar to that induced by NA or AD injections, suggesting that the hyperphagia after NA or AD treatment depends on α-2 adrenoceptors activation. Finally, we have demonstrated that CLO injections into DR impact neuronal activity in the ARC, possibly evoking a homeostatic response toward food intake.
本研究旨在评估药物干预背侧中缝核(DR)α-肾上腺素能激动剂对饱食大鼠摄食的影响。成年雄性 Wistar 大鼠在 DR 中植入慢性套管后,注射肾上腺素(AD)或去甲肾上腺素(NA)(剂量分别为 6、20 和 60 nmol),或 α-1 肾上腺素能激动剂苯肾上腺素(PHE)或 α-2 肾上腺素能激动剂可乐定(CLO)(剂量分别为 6 和 20 nmol)。注射后评估摄食行为。评估 60 分钟的食物和水摄入量。60 nmol AD 和 NA 以及 20 nmol CLO 的给药增加了饱食大鼠的食物摄入量并降低了开始进食的潜伏期。DR 中 PHE 处理对摄食行为没有显著影响。CLO 处理增加了允许在实验记录期间进食的大鼠弓状核(ARC)和下丘脑室旁核(PVN)中的 Fos 表达(AF 组)。然而,当实验过程中不提供食物时(WAF 组),PVN 神经元未被激活,而与对照组相比,ARC 中的神经元活性仍然很高。值得注意的是,ARC 中的 POMC 神经元在 AF 组中表达 Fos。然而,在 WAF 组中,尽管在 WAF 组中注射 CLO 后观察到非 POMC 细胞中的 Fos 表达增加,但在 ARC 中未观察到双标记 POMC/Fos 细胞。总之,本研究的数据表明,DR α-肾上腺素能受体的药理学激活影响饱食大鼠的摄食。DR 中 CLO 注射引起的摄食反应与 NA 或 AD 注射引起的摄食反应相似,提示 NA 或 AD 治疗后的多食反应依赖于 α-2 肾上腺素能受体的激活。最后,我们已经证明,DR 中 CLO 注射会影响 ARC 中的神经元活动,可能会引起摄食的稳态反应。