Neonatal handling induces alteration in progesterone secretion after sexual behavior but not in angiotensin II receptor density in the medial amygdala: Implications for reproductive success Ca ´rmen Marilei Gomes a , Ma ´rcio Vinı ´cius Fagundes Donadio a , Janete Anselmo-Franci b , Celso Rodrigues Franci c , Aldo Bolten Lucion a , Gilberto Luiz Sanvitto a, * a Laborato ´rio de Neuroendocrinologia do Comportamento, Departamento de Fisiologia, Instituto de Cie ˆncias Ba ´sicas da Sau ´de (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite 500, Porto Alegre, Rio Grande do Sul (RS), 90050-170, Brazil b Laborato ´rio de Neuroendocrinologia, Departamento de Fisiologia, Morfologia e Estomatologia, Faculdade de Odontologia de Ribeira ˜o Preto, Universidade de Sa ˜o Paulo, Ribeira ˜o Preto, Sa ˜o Paulo (SP), Brazil c Departamento de Fisiologia, Faculdade de Medicina de Ribeira ˜o Preto, Universidade de Sa ˜o Paulo, Ribeira ˜o Preto, Sa ˜o Paulo (SP), Brazil Received 20 June 2005; accepted 7 November 2005 Abstract Neonatal handling affects the hypothalamus – pituitary – gonadal axis in female rats. Indeed, postnatal handling induces anovulatory estrous cycles and decreases sexual receptiveness. On the other hand, Angiotensin II (Ang II) infused into the medial amygdala (MeA) reduces sexual behavior in male and female rats. Considering this, and that gonadal steroid secretion after copulatory behavior is important for reproductive success, the purpose of the present study was to investigate whether the reduction in sexual receptiveness in neonatally handled female rats is mediated by changes in Ang II receptor density in MeA. Moreover, gonadal steroid secretion after sexual behavior was analyzed. Two groups of female Wistar rats were studied: nonhandled (pups were left undisturbed) and handled (pups were handled for 1 min once a day during the first 10 days of life). Once they were 80– 85 days old in the evening of the proestrus day, sexual receptiveness was recorded and after that the animals were killed by decapitation. Trunk blood samples were collected, and plasma estradiol and progesterone were measured by radioimmunoassay. The brains were removed for Ang II receptor autoradiography in MeA. The decreased lordosis quotient in the neonatally handled group was confirmed in the present study. Neonatal handling also reduced the progesterone concentration in the plasma, but did not change the estradiol and the density of Ang II receptors in MeA. The reduced progesterone could be due to the decreased lordosis frequency of handled females. However, this decreased sexual receptiveness is not mediated by changes in Ang II receptors in MeA. D 2005 Elsevier Inc. All rights reserved. Keywords: Neonatal handling; Female rats; Sexual behavior; Progesterone; Angiotensin II receptors; Medial amygdala Introduction Neonatal handling has been used as an experimental model to examine the mechanisms by which early environmental changes could affect neural systems, leading to stable behavioral and neuroendocrine changes (Meerlo et al., 1999). In rats, early postnatal handling reduces emotional responses in adulthood, which is expressed as an increased exploratory activity and interpreted as a decreased fear of novel environments (Levine et al., 1967; Meerlo et al., 1999). Postnatally handled rats, as adults, synthesize and secrete less corticotrophin-releasing hormone (CRH), adrenocorticotrophin (ACTH) and corticoste- rone to a wide variety of stressors and show a faster return to basal levels following the termination of the stimulus (Levine et al., 1967; Liu et al., 2000). Moreover, neonatal handling increases the expression of glucocorticoid receptors in the hippocampus and frontal cortex, which explains the increased stress negative feedback (Meaney et al., 1985). Neonatal stimulation may affect not only the hypothalamus – pituitary–adrenal axis, as previously demonstrated (Levine et al., 1967; Liu et al., 2000; Meerlo et al., 1999; Padoin et al., 2001), but also the hypothalamus–pituitary–gonadal (HPG) axis (Gomes et al., 1999, 2005; Padoin et al., 2001). In fact, 0024-3205/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.lfs.2005.11.007 * Corresponding author. Tel.: +55 51 3316 3359; fax: +55 51 3316 3656. E-mail address: sanvitto@portoweb.com.br (G.L. Sanvitto). Life Sciences 78 (2006) 2867 – 2871 www.elsevier.com/locate/lifescie