Early stimulation has been shown to produce long-lasting effects in many species. Prenatal exposure to some strong stressors may affect development of the nervous system leading to behavioral impairment in adult life. The purpose of the present work was to study the postnatal harmful effects of exposure to variable mild stresses in rats during pregnancy. Female Holtzman rats were submitted daily to one session of a chronic variable stress (CVS) during pregnancy (prenatal stress; PS group). Control pregnant rats (C group) were undisturbed. The pups of PS and C dams were weighed and separated into two groups 48 h after delivery. One group was maintained with their own dams (PS group, N = 70; C group, N = 36) while the other PS pups were cross-fostered with C dams (PSF group, N = 47) and the other C pups were cross-fostered with PS dams (CF group, N = 58). Pups were undisturbed until weaning (postnatal day 28). The male offspring underwent motor activity tests (day 28), enriched environment tests (day 37) and social interaction tests (day 42) in an animal activity monitor. Body weight was recorded on days 2, 28 and 60. The PS pups showed lower birth weight than C pups (Duncans test, P<0.05). The PS pups suckling with their stressed mothers displayed greater preweaning mortality (C: 23%, PS: 60%; c 2 test, P<0.05) and lower body weight than controls at days 28 and 60 (Duncans test, P<0.05 and P<0.01, respectively). The PS, PSF and CF groups showed lower motor activity scores than controls when tested at day 28 (Duncans test, P<0.01 for PS group and P<0.05 for CF and PSF groups). In the enriched environment test performed on day 37, between-group differences in total motor activity were not detected; however, the PS, CF and PSF groups displayed less exploration time than controls (Duncans test, P<0.05). Only the PS group showed impaired motor activity and impaired social behavior at day 42 (Duncans test, P<0.05). In fact, CVS treatment during gestation plus suckling with a previously stressed mother caused long-lasting physical and behavioral changes in rats. Cross-fostering PS-exposed pups to a dam which was not submitted to stress counteracted most of the harmful effects of the treatment. It is probable that prenatal stress plus suckling from a previously stressed mother can induce long-lasting changes in the neurotransmitter systems involved in emotional regulation. Further experiments using neurochemical and pharmacological approaches would be interesting in this model. Correspondence

We have reported that exposure of preweaning male and female rats to a model of unpredictable mild physical stressors (Neo-A) can decrease the behavioral and hormonal responses to acute and chronic stress as adults. In this paper we have analyzed the effect of Neo-A on development of social behaviors, including aggressiveness, social dominance, and sexual behavior in adulthood. The subjects were divided into two groups: Neo-A (daily exposed to unpredictable mild stresses- from day 2 up to day 15 of suckling; n = 30 litters) and controls (C) (undisturbed rats, except for testing, during the same period of life; n = 26 litters). When day 6 pups were submitted to a social clustering test the Neo-A group showed a higher rate of litter-mate clustering than C. The 35 days Neo-A males and Neo-A females submitted to a social behavior test after 24 h of social isolation also showed higher scores of time spent in active social interaction than controls, as well as a higher ratio of animals showing aggressive playing. A second social behavior test performed after 48 h of social isolation at days 75-80 of age revealed that only Neo-A females displayed increased social behavior and aggressive behaviors, whereas controls did not. A water competition test performed at 24 and 48 h after water deprivation showed that Neo-A adult males spent more time in possession of the drinking device and drank more frequently than C. When adult proestrous females were exposed to a sexual behavior test, the Neo-A group showed shorter latency and higher scores of lordosis quotient. These results support the view that exposure to this model of repeated mild stress early in life stimulates the development of social behavior, dominance and sexual behavior.

El rol de las hormonas sexuales sobre el comportamiento reproductivo ha sido extensamente documentado. La fluctuación periódica de hormonas sexuales en hembras de numerosas especies ha sido relacionada con cambios comportamentales no sexuales tales como humor, ansie dad, agresión y respuesta a estrés. El sustrato bioló-gico-neural de estos cambios se basa en los cambios que estas hormonas inducen en el Sistema Nervioso Central. Este trabajo resume algunos cambios que afectan a receptores y neurotrasmisores de los sistemas GABAérgico, serotoninér-gico, dopaminérgico y péptido liberador de prolactina del SNC de la rata. La rata hembra posee un ciclo sexual de 4 días de duración, denominado ciclo estrual. La presente revisión se informa en tres secciones. (1) Se presenta una breve descripción de la variación de tres hormonas sexuales principales con acción directa sobre el SNC: estrógenos (E2), progesterona (P4) y prolactina (PRL). Se han descripto propiedades ansiolíticas para P4 y anti-estrés para PRL; para E2, la bibliografía es controvertida, describiéndose acciones excitatorias y anti-estrés. (2) Se informan algunos cambios cerebrales y comportamentales que tienen lugar en cada estadio del ciclo estrual. Las fluctuaciones hormonales se consideran bá-sicas para la interpretación de tales cambios. (3) Se mencionan algunos hallazgos acerca de la influencia hormonal cíclica sobre los sistemas de neurotransmisión del SNC y sobre un nuevo pép-tido propuesto como mediador de la respuesta a INTERDISCIPLINARIA, 2012, 29, 1, 63-77 63 INFLUENCE OF THE ESTROUS ABSTRACTSex hormone fluctuations in females are involv ed in some behavioral states such as mood, anxiety, aggression and stress response, due to functional changes in the central nervous system (CNS) activity induced by the cyclic sex hormone fluctuation. This review includes three sections.1.-A description of the three major hormone fluctuations in the estrous cycle: estrogens (E2), progesterone (P4) and prolactine (PRL). E2 achieves the maximum circulation levels during P. E2 is mainly excitatory and has been considered to have an antidepressive action. The highest plasma levels of P4 and its metabolite allopregnenolone (ALLO) occur in P. Ovulation takes place in the night of P, and the resulting corpora lutea produces a secondary increase in P4 (and ALLO) on D. The P4 peak level occurring in D1 and in the evening of P was shown to exert benzodiazepine-like effects, including sedation. It has been proposed that ALLO, rather than P4 is the one acting on GABA systems. Circulating levels of ALLO parallel those of P4 across the estrous cycle and is known to have anxiolytic properties.PRL is produced mainly in the adeno hy pophysis, though synthesis in other sites of the brain also occurs. Its regulation is mostly inhibitory and is exerted by dopamine (DA) released in the hypothalamus. A surge in PRL secretion occurs during P. PRL would be a modulator of the HPA-axis, and is considered as a stress hormone.2.-Some behavioral and neural changes occur at each stage ...

The probable role of prolactin (PRL) on the behavioral responses evoked by chronic unpredictable stress (CUS) was studied in adult male rats. Three experiments were performed examining the effect of CUS on behavioral performance in: (i) intact rats with normal endogenous PRL levels, (ii) rats with high endogenous PRL levels, and (iii) rats with low endogenous PRL levels. Behavioral parameters studied were: locomotion, head-dipping, rearing and grooming. Endocrine parameters studied were: PRL and corticosterone (C) plasma concentrations. In Experiment (i) results showed that CUS inhibited significantly locomotion, head-dipping and rearing activity. No variations in PRL plasma levels were found but a significant increase in C was detected. In Experiment (ii) the hyperprolactinaemia induced by pituitary transplants in the kidney capsule blocked partially the inhibition of locomotion due to CUS. No modifications on head-dipping, rearing and grooming were observed. PRL levels in these rats were consistently high as expected and CUS regimen did not change the hormone concentrations in blood. The C response due to CUS, however was completely blocked in the pituitary-implanted group. In Experiment (iii), repeated treatment with bromocriptine (5 mg/kg i.p.) significantly increased the inhibitory effect of CUS on locomotion, head-dipping and rearing. Grooming was also decreased in CUS-treated rats. PRL levels in these animals was low as expected and the C response due to CUS was significantly increased. Results give support to the concept that PRL may have a regulatory role in CUS.