Bhattacharya S K, Chakrabarti A, Sandler M, Glover V
Department of Pharmacology, Banaras Hindu University, Varanasi, India.
Neuropsychopharmacology. 1996 Aug;15(2):199-206. doi: 10.1016/0893-133X(95)00204-Q.
Rat atrial natriuretic peptide (ANP) was investigated for putative anxiolytic activity in rats, following intracerebroventricular (ICV) administration. ANP in doses of 200 and 500 ng/rat induced significant anxiolysis, comparable with that of lorazepam (0.5 mg/kg, i.p.) in a variety of anxiety models (open-field, elevated plus-maze, social interaction, and novelty-induced feeding suppression tests). Isatin, an endogenous anxiogenic indole, shown to be an antagonist of ANP in vitro, significantly inhibited the anxiolytic effect of ANP in the elevated plus-maze test in subanxiogenic doses. The anxiolytic action of ANP was unaffected by flumazenil, a benzodiazepine receptor antagonist. Conversely, the anxiolytic action of lorazepam was antagonized by flumazenil but not by isatin. The data indicate that ANP may function as an endogenous anxiomodulator, which may act in conjunction with isatin independently of benzodiazepine receptors. These results strengthen the evidence for links between physiological systems involved in anxiety and those in natriuresis.
研究了大鼠脑室内注射心房钠尿肽(ANP)后的假定抗焦虑活性。在各种焦虑模型(旷场试验、高架十字迷宫试验、社交互动试验和新奇诱导摄食抑制试验)中,200和500 ng/大鼠剂量的ANP诱导出显著的抗焦虑作用,与劳拉西泮(0.5 mg/kg,腹腔注射)相当。异吲哚酮是一种内源性致焦虑吲哚,在体外被证明是ANP的拮抗剂,在亚致焦虑剂量下,它在高架十字迷宫试验中显著抑制了ANP的抗焦虑作用。ANP的抗焦虑作用不受苯二氮䓬受体拮抗剂氟马西尼的影响。相反,劳拉西泮的抗焦虑作用被氟马西尼拮抗,但不受异吲哚酮的影响。数据表明,ANP可能作为一种内源性焦虑调节因子发挥作用,它可能与异吲哚酮协同作用,独立于苯二氮䓬受体。这些结果加强了参与焦虑的生理系统与利钠系统之间存在联系的证据。