Effects of Angiotensin II Microinjected into Medial Amygdala on Male Sexual Behavior in Rats M. K. Breigeiron,* M. Morris,† A. B. Lucion,* and G. L. Sanvitto* ,1 *Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; and †Department of Pharmacology and Toxicology, Wright State University School of Medicine, Dayton, Ohio Received December 1, 2000; revised June 4, 2001; accepted October 9, 2001 Research was undertaken to study the role of central angiotensin in the modulation of male sexual behavior, testing the effect of angiotensin II (Ang II) injections into the medial amygdaloid nucleus (MeA). The sexual behav- ior of adult male Wistar rats was evaluated, 15 min after bilateral intra-amygdaloid microinjection (0.3 l) of sa- line and 5 doses of Ang II: 10; 25; 50; 100, and 150 fmol. The effects of the Ang II receptor blockade were also studied. We tested the effect of coinjection of Ang II (50 fmol) with the AT 1 antagonist, losartan (20 pmol) and the AT 2 antagonist, CGP 42112 (1 pmol). Ang II inhibited sexual behavior and this inhibition was prevented by the coinjection of AT 1 antagonist, losartan, or the AT 2 antag- onist, CGP 42112. Results show that Ang II has a pow- erful effect on male sexual behavior, which may be me- diated by both AT 1 and AT 2 receptors. © 2002 Elsevier Science (USA) Key Words: angiotensin II; medial amygdala; losartan; angiotensin II receptors; sexual behavior; rat. Ang II is a regulatory peptide well known for its role in the control of fluid balance and autonomic and cardiovascular functions (Saavedra, 1992; Sanvitto, Joh- ren, Hauser, and Saavedra, 1997; Thunhorst, Morris, and Johnson 1994; Morris, Li, Callahan, Oliverio, Coff- man, Bosch, and Diz, 1999). Ang II is also well recog- nized as an actor in the pathogenesis of experimental and clinical hypertension (Unger, Kauffamn-Buhler, Scholkens, and Banten, 1981). Blockade of Ang II for- mation by angiotensin converting enzyme inhibition is one of the standard therapies in human essential hypertension. Results obtained in animal models sup- port the hypothesis that an overactive brain angio- tensinergic system is involved in the development and maintenance of hypertension (Gyurko, Wielbo, and Phillips, 1993; Phillips, Mann, Haebara, Hoffmann, Dietz, Schelling, and Ganten, 1977). On the other hand, with the exception of drinking, there is little information on the role of angiotensin in behavior. Hypertension is associated with an increased inci- dence of sexual dysfunction; however, the under- standing of this relationship is still controversial (Feld- man, Goldstein, Hatzichristou, Krane, and McKinlay, 1994; Muller, Damanhoury, Ruth, and Lue, 1991; Bul- pitt, Dollery, and Carne, 1976). Many new antihyper- tensive drugs, like losartan, act by antagonizing the effect of Ang II at the level of the AT 1 receptor (Li, Touyz, and Schiffrin, 1998). It is suggested that one of the advantages of losartan compared to the classical antihypertensive drugs is the lack of effect on quality of life, for example, on sexual function (Chan, Liu, Tong, Chen, Wang, Tomlinson, and Cheng, 1999). Over the past few years, it has been shown that Ang II may regulate the functions of the hypothalamo– pituitary– gonadal axis. The presence of Ang II, dem- onstrated by immunohistochemistry (Lind, Swanson, and Ganten, 1985), as well as Ang II receptors, by in situ hybridization and binding techniques, were shown in brain areas that exert control on the repro- ductive function (Jo ¨ hren et al., 1997; Seltzer, Tsutsumi, Shigematsu, and Saavedra, 1993). The action of Ang II in the nervous system can be exerted by the peptide produced locally in the brain as well as by peripheral Ang II through the circumventricular organs (Saave- dra, 1992). 1 To whom correspondence and reprint requests should be ad- dressed. Fax: 55 (51) 3316-3453. E-mail: sanvitto@portoweb.com.br. Hormones and Behavior 41, 267–274 (2002) doi:10.1006/hbeh.2002.1771, available online at http://www.idealibrary.com on 0018-506X/02 $35.00 © 2002 Elsevier Science (USA) All rights reserved. 267