Pharmacological Research, Vol. 46, No. 1, 2002 doi:10.1016/S1043-6618(02)00038-5, available online at http://www.idealibrary.com on MONOAMINERGIC AND CHOLINERGIC STIMULATION OF MASCULINE SEXUAL BEHAVIOR IN NEONATALLY DEMASCULINIZED MALE RATS A. MORALES-OTAL, A. FERREIRA-NUÑO and J. VELÁZQUEZ-MOCTEZUMA ∗ Department of Reproductive Biology, Universidad Autonoma Metropolitana-Iztapalapa, Mexico City, CP 09340, Mexico Accepted 4 April 2002 Sexual behavior during adulthood largely depends upon hormonal events that take place around birth. Administration of the antiestrogen Tamoxifen (Tx) to males immediately after birth induces a marked decrease of masculine sexual behavior during adulthood. On the other hand, it is well known that masculine sexual behavior can be stimulated by the administration of drugs acting specifi- cally on the monoaminergic or the cholinergic systems. This study was performed to analyze if masculine sexual behavior can be pharmacologically stimulated in adult male rats neonatally demas- culinized by the administration of Tx. Neonatal administration of Tx induced clear impairments of masculine sexual behavior during adulthood. Administration of oxotremorine (OXO), 8-OH-DPAT (8-hydroxy-2(di-n-propylaminotetraline)), yohimbine (YH), and apomorphine (APO), drugs that normally elicit a stimulation of masculine sexual behavior were unable to fully restore it in de- masculinized males. Only slight improvements of some behavioral parameters were observed with 8-OH-DPAT and YH. OXO seems to induce a worsening of sexual behavior impairments. Results obtained with APO were not significantly different from saline controls. Data suggest that neona- tal treatment with Tx induces permanent impairments of the neural circuitry regulating masculine sexual behavior not only limited to morphological changes but also functional alterations of the neurotransmitter systems. © 2002 Elsevier Science Ltd. All rights reserved. Key words: sexual differentiation, yohimbine, 8-OH-DPAT, oxotremorine, apomorphine. INTRODUCTION It is well known that brain sexual differentiation in ro- dents takes place during the early stages of life and largely depends on the hormonal environment [1]. It has been reported that cerebral tissue is sensitive to hormonal influ- ences during a critical period which extends from the last days of gestation to approximately 5 days of age [2, 3]. During this period, normal brain sexual differentiation can be altered either by gonadectomy or by the exogenous administration of gonadal steroids [4]. Male rats neona- tally castrated display a decrease of masculine sexual behavior during adulthood. This effect can be prevented by neonatal administration of testosterone or estradiol [5]. Administration of the antiestrogen Tamoxifen (Tx) to new born male rats induces a marked loss of masculine sexual behavior during adulthood as well as an increase in feminine sexual behavior [6, 7]. ∗ Corresponding author. Departamento de Biolog´ ıa de la Reproducci ´ on, Universidad Aut´ onoma Metropolitana-Iztapalapa, CP 09340, Iztapalapa, D.F. M´ exico. E-mail: jvm@xanum.uam.mx On the other hand, it is now well established that mascu- line sexual behavior in rodents is regulated by the activity of several neurotransmitter systems [8–13]. Stimulation of masculine sexual behavior activity can be readily achieved by the administration of drugs that act specifi- cally on the receptors of some neurotransmitter system. Pharmacological agents that have repeatedly demon- strated their ability to improve sexual behavior in rodents are: yohimbine (YH), a selective blocker of the alpha-2 adrenergic receptors; apomorphine (APO), an agonist of the D 2 dopaminergic receptors; oxotremorine (OXO), an agonist of the muscarinic receptors; and 8-OH-DPAT (8-hydroxy-2(di-n-propylaminotetraline)), a selective ag- onist of the 5-HT 1A serotonergic receptors (for review see [9]). Besides their well known effect on sexual be- havior, all of these drugs readily cross the blood brain barrier, possess a high specificity for their receptors and their pharmacological actions have been widely studied in the last decade. Thus, in order to analyze if there are some impairments in the neurotransmitter systems in de- masculinized rats, the monoaminergic and the cholinergic systems seem to be a suitable choice as the first step. 1043-6618/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved.