{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:00:46Z","timestamp":1790992846003,"version":"4.1.0"},"reference-count":54,"publisher":"Portland Press Ltd.","issue":"14","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,7,1]]},"abstract":"<jats:p>Angiotensin-(1\u20137) [Ang-(1\u20137)], a counter-regulatory peptide of the renin\u2013angiotensin system (RAS) exerts its effects through the G-protein-coupled receptor Mas, which is expressed in different tissues, including the brain. Ang-(1\u20137) has a broad range of effects beyond the well-described cardiovascular and renal actions, including the modulation of emotional and behavioural responses. In the present study we tested the hypothesis that Ang-(1\u20137) could attenuate the anxiety- and depression-like behaviours observed in transgenic hypertensive (mRen2)27 rats (TGRs). We also hypothesized that Ang-(1\u20137) could be involved in the anxiolytic-like effect induced by ACE (angiotensin-converting enzyme) treatment in these hypertensive rats. Therefore, TGRs and Sprague\u2013Dawley rats were subjected to the Elevated Plus Maze (EPM) test, Forced Swimming Test (FST) and Novelty Suppressed Feeding (NSF). TGRs presented a decreased percentage of entries in the open arms of the EPM test, a phenotype reversed by systemic treatment with enalapril or intracerebroventricular infusion of Ang-(1\u20137). It is interesting that pre-treatment with A779, a selective Mas receptor antagonist, prevented the anxiolytic-like effect induced by the ACE inhibitor. In the NSF test, TGRs showed increased latency to eating, an indicative of a higher aversion in response to a new environment. These animals also showed increased immobility in the FST. Again, Ang-(1\u20137) reversed this phenotype. Thus, our data showed that Ang-(1\u20137) can modulate anxiety- and depression-like behaviours in TGRs and warrant further investigation as a new therapy for certain psychiatric disorders.<\/jats:p>","DOI":"10.1042\/cs20160116","type":"journal-article","created":{"date-parts":[[2016,4,21]],"date-time":"2016-04-21T05:33:58Z","timestamp":1461216838000},"page":"1247-1255","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Anxiolytic- and antidepressant-like effects of angiotensin-(1\u20137) in hypertensive transgenic (mRen2)27 rats"],"prefix":"10.1042","volume":"130","author":[{"given":"Ana\u00a0Fl\u00e1via","family":"Almeida-Santos","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil"},{"name":"Department of Pharmacology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas\u00a0M.","family":"Kangussu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabr\u00edcio\u00a0A.","family":"Moreira","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robson\u00a0A.S.","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele\u00a0C.","family":"Aguiar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria\u00a0Jos\u00e9","family":"Campagnole-Santos","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2016,6,13]]},"reference":[{"key":"2021113010462019800_B1","first-page":"48","article-title":"Role of the renin\u2013angiotensin system in control of sodium excretion and arterial pressure","volume":"591","author":"Hall","year":"1990","journal-title":"Acta Physiol. Scand. Suppl."},{"key":"2021113010462019800_B2","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/S1054-3589(10)59007-0","article-title":"Advances in the renin\u2013angiotensin system focus on angiotensin-converting enzyme 2 and angiotensin-(1\u20137)","volume":"59","author":"Ferrario","year":"2010","journal-title":"Adv. Pharmacol."},{"key":"2021113010462019800_B3","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1161\/HYPERTENSIONAHA.113.01274","article-title":"Angiotensin-(1\u20137)","volume":"63","author":"Santos","year":"2014","journal-title":"Hypertension"},{"key":"2021113010462019800_B4","doi-asserted-by":"publisher","first-page":"8258","DOI":"10.1073\/pnas.1432869100","article-title":"Angiotensin-(1\u20137) is an endogenous ligand for the G protein-coupled receptor Mas","volume":"100","author":"Santos","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113010462019800_B5","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/0014-5793(94)01292-9","article-title":"Expression of the mouse and rat mas proto-oncogene in the brain and peripheral tissues","volume":"357","author":"Metzger","year":"1995","journal-title":"FEBS Lett."},{"key":"2021113010462019800_B6","doi-asserted-by":"publisher","first-page":"H1416","DOI":"10.1152\/ajpheart.00141.2007","article-title":"Immunofluorescence localization of the receptor Mas in cardiovascular-related areas of the rat brain","volume":"293","author":"Becker","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2021113010462019800_B7","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1042\/CS20120461","article-title":"Angiotensin-(1\u20137): beyond the cardio-renal actions","volume":"124","author":"Passos-Silva","year":"2013","journal-title":"Clin. Sci. (Lond.)"},{"key":"2021113010462019800_B8","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.nlm.2011.10.003","article-title":"Angiotensin-(1-7)\/Mas axis integrity is required for the expression of object recognition memory","volume":"97","author":"Lazaroni","year":"2012","journal-title":"Neurobiol. Learn. Mem."},{"key":"2021113010462019800_B9","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.mcn.2005.03.012","article-title":"Angiotensin-(1\u20137) enhances LTP in the hippocampus through the G-protein-coupled receptor Mas","volume":"29","author":"Hellner","year":"2005","journal-title":"Mol. Cell Neurosci."},{"key":"2021113010462019800_B10","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.jad.2012.07.024","article-title":"Angiotensin-(1\u20137) central administration induces anxiolytic-like effects in elevated plus maze and decreased oxidative stress in the amygdala","volume":"145","author":"Bild","year":"2013","journal-title":"J. Affect. Disord."},{"key":"2021113010462019800_B11","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1113\/expphysiol.2007.040345","article-title":"Genetically altered animal models for Mas and angiotensin-(1\u20137)","volume":"93","author":"Alenina","year":"2008","journal-title":"Exp. Physiol"},{"key":"2021113010462019800_B12","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.bbr.2013.09.003","article-title":"Angiotensin-(1\u20137) attenuates the anxiety and depression-like behaviors in transgenic rats with low brain angiotensinogen","volume":"257","author":"Kangussu","year":"2013","journal-title":"Behav. Brain Res."},{"key":"2021113010462019800_B13","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1038\/nn.4086","article-title":"Mechanisms of stress in the brain","volume":"18","author":"McEwen","year":"2015","journal-title":"Nat. Neurosci."},{"key":"2021113010462019800_B14","doi-asserted-by":"crossref","first-page":"261","DOI":"10.31887\/DCNS.2015.17.3\/sbrooks","article-title":"A systematic review of the neural bases of psychotherapy for anxiety and related disorders","volume":"17","author":"Brooks","year":"2015","journal-title":"Dialogues Clin. Neurosci."},{"key":"2021113010462019800_B15","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1002\/da.22227","article-title":"Neurobiology of stress, depression, and rapid acting antidepressants: remodeling synaptic connections","volume":"31","author":"Duman","year":"2014","journal-title":"Depress. Anxiety"},{"key":"2021113010462019800_B16","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.neubiorev.2014.03.020","article-title":"Executive and modulatory neural circuits of defensive reactions: implications for panic disorder","volume":"46","author":"Canteras","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"2021113010462019800_B17","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/344541a0","article-title":"Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene","volume":"344","author":"Mullins","year":"1990","journal-title":"Nature"},{"key":"2021113010462019800_B18","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S0924-977X(98)00031-5","article-title":"Hippocampal 5-HT and NE release in the transgenic rat TGR(mRen2)27 related to behavior on the elevated plus maze","volume":"9","author":"Voigt","year":"1999","journal-title":"Eur. Neuropsychopharmacol."},{"key":"2021113010462019800_B19","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.brainres.2005.03.048","article-title":"Brain angiotensin and anxiety-related behavior: the transgenic rat TGR(ASrAOGEN)680","volume":"1046","author":"Voigt","year":"2005","journal-title":"Brain Res."},{"key":"2021113010462019800_B20","first-page":"1","article-title":"Behaviour of the transgenic (mRen2)27 rat","volume":"729","author":"Wilson","year":"1996","journal-title":"Brain Res."},{"key":"2021113010462019800_B21","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1016\/0006-3223(86)90334-3","article-title":"Captopril treatment of depression","volume":"21","author":"Deicken","year":"1986","journal-title":"Biol. Psychiatry"},{"key":"2021113010462019800_B22","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1161\/01.HYP.23.4.439","article-title":"Effects of converting enzyme inhibitors on angiotensin and bradykinin peptides","volume":"23","author":"Campbell","year":"1994","journal-title":"Hypertension"},{"key":"2021113010462019800_B23","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/0196-9781(93)90063-M","article-title":"Angiotensin(1\u20137) in the spontaneously hypertensive rat","volume":"14","author":"Kohara","year":"1993","journal-title":"Peptides"},{"key":"2021113010462019800_B24","volume-title":"The Rat Brain in Stereotaxic Coordinates","author":"Paxinos","year":"1997","edition":"3rd edn"},{"key":"2021113010462019800_B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/BF00504983","article-title":"Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of \u2018fear\u2019-motivated behaviour","volume":"327","author":"Handley","year":"1984","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"2021113010462019800_B26","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.bbr.2013.05.027","article-title":"Modulation of anxiety-like behavior by the endocannabinoid 2-arachidonoylglycerol (2-AG) in the dorsolateral periaqueductal gray","volume":"252","author":"Almeida-Santos","year":"2013","journal-title":"Behav. Brain Res."},{"key":"2021113010462019800_B27","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1161\/01.HYP.7.2.244","article-title":"An improved fluorometric assay of rat serum and plasma converting enzyme","volume":"7","author":"Santos","year":"1985","journal-title":"Hypertension"},{"key":"2021113010462019800_B28","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1007\/BF00181937","article-title":"The effects of chronic antidepressant treatment in an animal model of anxiety","volume":"95","author":"Bodnoff","year":"1988","journal-title":"Psychopharmacology (Berl.)"},{"key":"2021113010462019800_B29","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/BF00442264","article-title":"A comparison of the effects of diazepam versus several typical and atypical anti-depressant drugs in an animal model of anxiety","volume":"97","author":"Bodnoff","year":"1989","journal-title":"Psychopharmacology (Berl.)"},{"key":"2021113010462019800_B30","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/S0165-6147(02)02017-5","article-title":"Assessing antidepressant activity in rodents: recent developments and future needs","volume":"23","author":"Cryan","year":"2002","journal-title":"Trends Pharmacol. Sci."},{"key":"2021113010462019800_B31","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1038\/266730a0","article-title":"Depression: a new animal model sensitive to antidepressant treatments","volume":"266","author":"Porsolt","year":"1977","journal-title":"Nature"},{"key":"2021113010462019800_B32","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1113\/expphysiol.2011.058578","article-title":"Cerebroprotection by angiotensin-(1\u20137) in endothelin-1-induced ischaemic stroke","volume":"96","author":"Mecca","year":"2011","journal-title":"Exp. Physiol."},{"key":"2021113010462019800_B33","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.fertnstert.2010.06.060","article-title":"Angiotensin-(1\u20137), its receptor Mas, and the angiotensin-converting enzyme type\u00a02 are expressed in the human ovary","volume":"95","author":"Reis","year":"2011","journal-title":"Fertil. Steril."},{"key":"2021113010462019800_B34","doi-asserted-by":"publisher","first-page":"5569","DOI":"10.4049\/jimmunol.1000314","article-title":"Anti-inflammatory effects of the activation of the angiotensin-(1\u20137) receptor, MAS, in experimental models of arthritis","volume":"185","author":"da Silveira","year":"2010","journal-title":"J. Immunol."},{"key":"2021113010462019800_B35","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1176\/ajp.141.10.1306","article-title":"Mood-elevating effect of captopril in depressed patients","volume":"141","author":"Zubenko","year":"1984","journal-title":"Am. J. Psychiatry."},{"key":"2021113010462019800_B36","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1056\/NEJM198606263142602","article-title":"The effects of antihypertensive therapy on the quality of life","volume":"314","author":"Croog","year":"1986","journal-title":"N. Engl. J. Med."},{"key":"2021113010462019800_B37","first-page":"133","article-title":"Differential effects of antihypertensive medications on cognitive functioning","volume":"25","author":"Sudilovsky","year":"1989","journal-title":"Psychopharmacol. Bull."},{"key":"2021113010462019800_B38","doi-asserted-by":"publisher","first-page":"3880","DOI":"10.1210\/endo.142.9.8366","article-title":"Peripheral administration of an angiotensin II AT(1) receptor antagonist decreases the hypothalamic\u2013pituitary\u2013adrenal response to isolation stress","volume":"142","author":"Armando","year":"2001","journal-title":"Endocrinology"},{"key":"2021113010462019800_B39","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1515\/JBCPP.2003.14.4.323","article-title":"Captopril and enalapril improve cognition and depressed mood in hypertensive patients","volume":"14","author":"Braszko","year":"2003","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"2021113010462019800_B40","first-page":"591","article-title":"(The effect of enalapril and captopril on emotional processes in hypertensive patients)","volume":"36","author":"Karwowska-Polecka","year":"2002","journal-title":"Psychiatr. Pol."},{"key":"2021113010462019800_B41","first-page":"271","article-title":"Effects of angiotensin II and its receptor antagonists on motor activity and anxiety in rats","volume":"54","author":"Braszko","year":"2003","journal-title":"J. Physiol. Pharmacol."},{"key":"2021113010462019800_B42","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/S1734-1140(12)70730-2","article-title":"Anxiolytic-like effect of losartan injected into amygdala of the acutely stressed rats","volume":"64","author":"Llano Lopez","year":"2012","journal-title":"Pharmacol. Rep."},{"key":"2021113010462019800_B43","first-page":"183248","article-title":"Fear-potentiated behaviour is modulated by central amygdala angiotensin II AT1 receptors stimulation","volume":"2014","author":"Marinzalda Mde","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"2021113010462019800_B44","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.pbb.2014.05.006","article-title":"Valsartan reverses depressive\/anxiety-like behavior and induces hippocampal neurogenesis and expression of BDNF protein in unpredictable chronic mild stress mice","volume":"124","author":"Ping","year":"2014","journal-title":"Pharmacol. Biochem. Behav."},{"key":"2021113010462019800_B45","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1152\/physrev.1977.57.2.313","article-title":"Renin\u2013angiotensin system: biochemistry and mechanisms of action","volume":"57","author":"Peach","year":"1977","journal-title":"Physiol. Rev."},{"key":"2021113010462019800_B46","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1161\/01.HYP.31.1.362","article-title":"Metabolism of angiotensin-(1\u20137) by angiotensin-converting enzyme","volume":"31","author":"Chappell","year":"1998","journal-title":"Hypertension"},{"key":"2021113010462019800_B47","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1161\/01.HYP.37.5.1309","article-title":"Baroreflex improvement in shr after ace inhibition involves angiotensin-(1\u20137)","volume":"37","author":"Heringer-Walther","year":"2001","journal-title":"Hypertension"},{"key":"2021113010462019800_B48","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1161\/01.HYP.30.3.549","article-title":"Role of angiotensin-(1\u20137) in the modulation of the baroreflex in renovascular hypertensive rats","volume":"30","author":"Britto","year":"1997","journal-title":"Hypertension"},{"key":"2021113010462019800_B49","first-page":"32","article-title":"Effect of angiotensin II on the Vogel conflict paradigm and on the content of dopamine and noradrenaline in rat brain","volume":"16","author":"Georgiev","year":"1990","journal-title":"Acta Physiol. Pharmacol. Bulg."},{"key":"2021113010462019800_B50","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/S0143-4179(97)90021-4","article-title":"Behavioral effects of angiotensin II microinjected into CA1 hippocampal area","volume":"31","author":"Belcheva","year":"1997","journal-title":"Neuropeptides"},{"key":"2021113010462019800_B51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0014-2999(02)01283-9","article-title":"The role of angiotensin II in cognition and behaviour","volume":"438","author":"Gard","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"2021113010462019800_B52","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.brainres.2012.02.021","article-title":"Cardiovascular responses evoked by activation or blockade of GABA(A) receptors in the hypothalamic PVN are attenuated in transgenic rats with low brain angiotensinogen","volume":"1448","author":"Gomes da Silva","year":"2012","journal-title":"Brain Res."},{"key":"2021113010462019800_B53","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/0196-9781(94)90051-5","article-title":"Increased expression of angiotensin peptides in the brain of transgenic hypertensive rats","volume":"15","author":"Senanayake","year":"1994","journal-title":"Peptides"},{"key":"2021113010462019800_B54","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1038\/nprot.2012.044","article-title":"Using the rat forced swim test to assess antidepressant-like activity in rodents","volume":"7","author":"Slattery","year":"2012","journal-title":"Nat. Protoc."}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/130\/14\/1247\/447862\/cs1301247.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/130\/14\/1247\/447862\/cs1301247.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T11:34:17Z","timestamp":1638272057000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/130\/14\/1247\/71499\/Anxiolytic-and-antidepressant-like-effects-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,13]]},"references-count":54,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2016,7,1]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20160116","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,13]]}}}