RESUMO
Learning processes in rats during early development are importantly mediated by the mother, which represents the primary source of environmental information. This study aimed to determine whether aversive early experiences can induce the expression of pups' fear responses toward a non-aversive stimulus as a consequence of a memory process. First, we determined pups' fear responses toward an anesthetized female after being exposed to this stimulus or an empty cage together with their mothers from Postnatal Day (PNDs) 1 to 4. Second, we evaluated if the administration of the protein synthesis inhibitor cycloheximide (CHX; 0.2 mg/kg, subcutaneously (sc).) disrupted the reconsolidation processes and abolished the fear response on PND 9. Only female pups previously exposed to the female intruder expressed fear responses toward an anesthetized female on PND 8. CHX administration to female pups immediately after exposure to an anesthetized female on PND 8 suppressed fear responses on PND 9, indicating that the fear expression was the result of a memory process, probably mediated by the mother. These findings demonstrated that early experiences can shape responses to social stimuli in a sex-dependent manner and emphasize the critical role of the mother in influencing fear learning in a social context.
Assuntos
Memória , Mães , Ratos , Animais , Feminino , Humanos , Medo/fisiologia , Aprendizagem , AfetoRESUMO
Maternal behavior in mammals encompasses a complex repertoire of activities that ensure the survival of the offspring and shape their neural and behavioral development. The laboratory rat has been employed as a classic model for investigating maternal behavior, and recently with the use of advanced techniques, the knowledge of its neural basis has been expanded significantly. However, the standard laboratory testing conditions in which rats take care of a single litter impose constraints on the study of maternal flexibility. Interestingly, the reproductive characteristics of this species, including the existence of a fertile postpartum estrus, allow us to study maternal behavior in more complex and ethologically relevant contexts, even in laboratory settings. Here we review how maternal and sexual motivations interact during the postpartum estrus, shaping the behavioral response of females according to the presence of the pups and males. Next, we describe how impregnation during the postpartum estrus creates a new reproductive context in which mothers simultaneously care for two successive litters, adapting their responses to different behavioral and physiological demands of pups. These findings illustrate the behavioral adaptability of maternal rats to pups' needs and the presence of other reinforcers, as well as its dependence on the context. In our view, future perspectives in the field, by incorporating the use of cutting-edge techniques, should analyze maternal flexibility and its neural substrates in models that incorporate complex and challenging contexts. This approach would allow a more comprehensive understanding of brain circuits involved in the adaptive and flexible nature of parenting.
RESUMO
Sexual behavior in the female rat is a highly motivated behavior first displayed during adolescence, a developmental period when neural circuits underlying motivation are not mature. This study characterizes the natural development of sexual motivation and behavior of female rats. We compared the incentive value of the male for mid-adolescent (PNDs:39-43), late adolescent (PNDs:49-53), and adult (PNDs:90-115) cycling females, using a male-female preference task and an ultrasonic vocalization emission test following exposure to a male or female stimulus animal. Furthermore, display of sexual and social behaviors during an interaction with a male or a nonreceptive female was assessed. Mid-adolescent rats exhibited a reduced preference for the male than adults and performed less attempts to access the male. Unlike late adolescent and adult females, mid-adolescent rats did not increase their ultrasonic vocalization emission after interacting with a male relative to a female. Although most of the sexual behavior did not differ between groups, mid-adolescent females showed lower lordosis magnitude and higher levels of play and social investigation during a sexual interaction, giving rise to a unique behavioral profile. Present results indicate that the sexual behavior repertoire is fully displayed by mid-adolescence, but sexual motivation is low and increases into late adolescence.
Assuntos
Motivação , Comportamento Sexual Animal , Animais , Feminino , Masculino , Ratos , Comportamento SocialRESUMO
The maternal behaviour of a rat dynamically changes during the postpartum period, adjusting to the characteristics and physiological needs of the pups. This adaptation has been attributed to functional modifications in the maternal circuitry. Maternal behaviour can also flexibly adapt according to different litter compositions. Thus, mothers with two overlapping litters can concurrently take care of neonate and juvenile pups, mostly directing their attention to the newborns. We hypothesised that the maternal circuitry of these mothers would show a differential activation pattern after interacting with pups depending on the developmental stage of their offspring. Thus, we evaluated the activation of several areas of the maternal circuitry in mothers of overlapping litters, using c-Fos immunoreactivity as a marker of neuronal activation, after interacting with newborns or juveniles. The results showed that mothers with overlapping litters display different behavioural responses towards their newborn and their juvenile pups. Interestingly, these behavioural displays co-occurred with specific patterns of activation of the maternal neural circuitry. Thus, a similar expression of c-Fos was observed in some key brain areas of mothers that interacted with newborns or juveniles, such as the medial preoptic area and the nucleus accumbens, whereas a differential activation was quantified in the ventral region of the bed nucleus of the stria terminalis, the infralimbic and prelimbic subregions of the medial prefrontal cortex and the basolateral and medial nuclei of the amygdala. We posit that the specific profile of activation of the neural circuitry controlling maternal behaviour in mothers with overlapping litters enables dams to respond adequately to the newborn and the juvenile pups.
Assuntos
Encéfalo/fisiologia , Comportamento Materno/fisiologia , Tonsila do Cerebelo/fisiologia , Animais , Animais Recém-Nascidos , Feminino , Masculino , Núcleo Accumbens/fisiologia , Córtex Pré-Frontal/fisiologia , Área Pré-Óptica/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Wistar , Núcleos Septais/fisiologiaRESUMO
HIGD1A (hypoxia-induced gene domain protein-1a), a mitochondrial inner membrane protein present in various cell types, has been mainly associated with anti-apoptotic processes in response to stressors. Our previous findings have shown that Higd1a mRNA is widely expressed across the central nervous system (CNS), exhibiting an increasing expression in the spinal cord from postnatal day 1 (P1) to 15 (P15) and changes in the distribution pattern from P1 to P90. During the first weeks of postnatal life, the great plasticity of the CNS is accompanied by cell death/survival decisions. So we first describe HIGD1A expression throughout the brain during early postnatal life in female and male pups. Secondly, based on the fact that in some areas this process is influenced by the sex of individuals, we explore HIGD1A expression in the sexual dimorphic nucleus (SDN) of the medial preoptic area, a region that is several folds larger in male than in female rats, partly due to sex differences in the process of apoptosis during this period. Immunohistochemical analysis revealed that HIGD1A is widely but unevenly expressed throughout the brain. Quantitative Western blot analysis of the parietal cortex, diencephalon, and spinal cord from both sexes at P1, P5, P8, and P15 showed that the expression of this protein is predominantly high and changes with age but not sex. Similarly, in the sexual dimorphic nucleus, the expression of HIGD1A varied according to age, but we were not able to detect significant differences in its expression according to sex. Altogether, these results suggest that HIGD1A protein is expressed in several areas of the central nervous system following a pattern that quantitatively changes with age but does not seem to change according to sex.
Assuntos
Sistema Nervoso Central/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Neoplasias/genética , Animais , Sistema Nervoso Central/crescimento & desenvolvimento , Feminino , Masculino , Ratos , Ratos WistarRESUMO
In rats, successful mating during the postpartum estrus results in the temporal overlapping of successive litters within the maternal nest. Mothers with two overlapping-litters (OLM) simultaneously take care of neonate and juvenile pups; however, they mostly direct their attention to the neonates. We hypothesized that these differences reflect an adaptation to the specific characteristics and needs of the two litters and not a lack of interest in the juveniles. To test this hypothesis, we assessed the relative incentive value of newborns and juveniles for OLM in a preference test and compared it with that exhibited by mothers in early (EPM) and late (LPM) postpartum, which were raising only newborns or only juveniles, respectively. Results showed that OLM spent similar time in the newborns and juveniles compartments and did not prefer the newborns as did the EPM, however, similarly to them, OLM made more attempts to get access to the newborns than the juveniles. On the other hand, OLM and LPM did not exhibit a clear preference between the stimuli. These results indicate that both neonates and juveniles have incentive value for OLM, although these mothers invest more effort in the newborns. These results point out to a unique behavioral profile of OLM, which shows similarities with EPM and LPM on different behavioral measures. They also support the idea that motivational processes underlying maternal behavior are complex and dynamic, adapting the response of the mother to pups' needs and the context.
Assuntos
Comportamento Animal/fisiologia , Comportamento Materno/fisiologia , Motivação/fisiologia , Fatores Etários , Animais , Animais Recém-Nascidos , Feminino , Masculino , Período Pós-Parto , Ratos , ReproduçãoRESUMO
Pups have greater incentive value than males for rats during the postpartum estrus (PPE); a period when females are both maternally and sexually motivated. Mesolimbic dopaminergic system has been proposed as a general motivational circuit; however in the literature it has been more related to the control of the motivational aspects of maternal than sexual motivation of females. Therefore, we aimed to assess the effect of antagonizing dopaminergic neurotransmission of PPE females on their preference for pups over a male. To achieve this objective we tested PPE rats in a Y-maze with three-choice chambers (one containing eight pups, the other a male and the last one no stimulus) after the systemic administration of the dopaminergic antagonist haloperidol (0.0; 0.025 or 0.05â¯mg/kg). Furthermore, to determine if this dopaminergic antagonist differentially affects maternal and sexual motivations when pups and male are not competing, we evaluated the effect of haloperidol in the preference of females for pups vs. a non-receptive female and for a male vs. a non-receptive female. In the preference test for pups vs. male, both doses of haloperidol decreased the time that females spent in pups' chamber while increased the time that they spent in male's chamber, resulting in a lack of preference between both incentives. Besides, haloperidol reduced the effort -attempts to get access to the stimuli- made by the females to obtain the pups. Conversely, 0.05â¯mg/kg of haloperidol did not affect the preference for both incentives when they were confronted to a non-receptive female. Together, these results indicate that the dopaminergic activity mediates pups' preference over male during the PPE and point toward a more relevant role of this system in females' behavioral output when incentives are competing.
Assuntos
Comportamento de Escolha/efeitos dos fármacos , Discriminação Psicológica/fisiologia , Dopamina/farmacologia , Estro/fisiologia , Comportamento Materno/fisiologia , Período Pós-Parto/metabolismo , Animais , Animais Recém-Nascidos , Antagonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Estro/efeitos dos fármacos , Estro/metabolismo , Feminino , Haloperidol/farmacologia , Masculino , Comportamento Materno/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Motivação , Período Pós-Parto/efeitos dos fármacos , Gravidez , Ratos , Ratos Wistar , Fatores Sexuais , Comportamento Sexual Animal/fisiologia , Estatísticas não ParamétricasRESUMO
During the stress hypo-responsive period, rat pups do not display fear responses toward adult males, yet they exhibit distress behavior in isolation. Since the mother modulates her offspring's affective development, we hypothesized that by altering the mother's behavior, a prolonged stressful situation would modify the ontogeny of the fear responses and distress behaviors in pups. Therefore, we repeatedly exposed the mother-litter dyad to different socially stressful stimuli and subsequently evaluated in 8-day-old pups their fear responses toward an anesthetized male, as well as their distress behavior in isolation. Our results show that repeated exposure to unfamiliar males and females, which altered maternal behavior by eliciting aggression in the mother, was associated with the precocious fear responses in pups, though without altering their distress behavior in isolation. We propose that the mother, as the principal mediator of environmental influences, provokes the precocious expression of fear in pups through alterations in her maternal behavior.
Assuntos
Comportamento Animal/fisiologia , Medo/fisiologia , Comportamento Materno/fisiologia , Estresse Psicológico/fisiopatologia , Vocalização Animal/fisiologia , Agressão/fisiologia , Animais , Animais Recém-Nascidos , Feminino , Masculino , Mães , Ratos , Ratos Wistar , Isolamento SocialRESUMO
We have investigated whether the chemical components of fetal fluids (FFs), which elicit repulsion in late gestating ewes, are also those responsible for the attractiveness of fetal fluids at parturition. An aqueous fraction of FFs (A1), obtained after extraction with hexane, was tested for repulsion in late-pregnant ewes and for attraction at parturition. We also investigated if the repulsive and attractive characteristics of this A1 fraction were maintained after an additional extraction with dichloromethane (DCM, CH(2)Cl(2)) that produced two more fractions (aqueous/high polarity: A2 and dichloromethane/medium polarity: DCM). Thus, late-pregnant ewes were tested for repulsion of aqueous extracts of FFs (A1, A2 and DCM fractions) in a two-choice test of food preference, whereas parturient ewes were tested for attraction toward these same fractions in a two-choice test of licking warm spongy cloths. The A1 fraction was repulsive to late-pregnant ewes and attractive to parturient females. In contrast, neither the A2 nor the DCM fractions were repulsive to late-pregnant ewes, whereas both fractions were attractive to parturient ones. The discordance between the repulsive and attractive properties of the A2 and DCM fractions suggests that the attractiveness of FFs for parturient ewes and its repulsiveness for females outside the peripartum period depend on mixtures of substances that are at least partially different. Some compounds with high and medium polarity in the A2 and DCM fractions would act synergistically to generate the repulsiveness of FFs, whereas both high and medium polarity compounds can evoke attraction independently of each other.
Assuntos
Líquido Amniótico/química , Comportamento Alimentar/fisiologia , Feto/química , Preferências Alimentares/fisiologia , Parto/metabolismo , Fatores Etários , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Recém-Nascidos , Comportamento de Escolha/efeitos dos fármacos , Comportamento de Escolha/fisiologia , Dexametasona/administração & dosagem , Comportamento Alimentar/efeitos dos fármacos , Feminino , Preferências Alimentares/efeitos dos fármacos , Idade Gestacional , Gravidez , Tempo de Reação/efeitos dos fármacos , Ovinos , Estatísticas não ParamétricasRESUMO
Several cellular and molecular events responsible for the development of the central nervous system (CNS), particularly those related to the development of ordered neural connections, occur during the first days of postnatal life, being days 1 through 10 a critical period to reach maturity and establish innervations. We have previously characterized hypoxia-induced gene 1 (Hig-1) and described an increase in its expression from day 1 to 15 of postnatal life in the spinal cord. Hig-1 mRNA has an open reading frame for a 93 amino acid protein, but its function has not been completely elucidated. Recently, several analyses in many cell types have related Hig-1 expression with differentiation or cell death/survival balance. With the aim of further characterizing the presence of Hig-1 in the CNS, we analyzed the cellular distribution of HIG-1 protein in rat's spinal cord at postnatal days 1, 8, 15, and 90 (P1-P90). We found an interesting change in the protein expression pattern, shifting from neurons at P1 to glial cells at P90, which points towards a functional role for this protein in the spinal cord throughout development. We also compared the protein distribution with the cellular distribution of the mRNA and of an antisense RNA.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Fator 1 Induzível por Hipóxia/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Medula Espinal/crescimento & desenvolvimento , Medula Espinal/fisiologia , Animais , Animais Recém-Nascidos , Biomarcadores/metabolismo , Fator 1 Induzível por Hipóxia/genética , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/fisiologia , Medula Espinal/citologiaRESUMO
The sexually active female rat solicits the male to approach for copulation, while the maternal dam displays aggression to expel him from the nest, suggesting that both behaviors are mutually exclusive. However, the rat has a postpartum estrus during which she is sexual and maternally motivated. Can she perceive the male as attractive and aversive, soliciting and attacking him at the same time? This study shows that postpartum estrous females exhibit a merge of sexual and maternal aggressive responses toward male intruders in the home cage. The concurrent expression of these behaviors did not affect their intensities, although the stimulation of maternal behavior increased maternal aggression without modifying sexual solicitation. These results indicate that the postpartum estrous rat can optimally express two opposite and independently regulated motivations, and that the male can be perceived as an ambivalent stimulus.
Assuntos
Agressão/psicologia , Comportamento Materno/psicologia , Motivação/fisiologia , Comportamento Sexual Animal/fisiologia , Agressão/fisiologia , Animais , Estro , Feminino , Masculino , Comportamento Materno/fisiologia , Período Pós-Parto/psicologia , Ratos , Ratos WistarRESUMO
Female rats show postpartum estrus, a unique stage in their reproductive cycle in which they are able to display maternal and sexual responses at the same time. To assess the relative value of pups or males for sexually receptive mothers with different hormonal profiles and reproductive experiences, we employed a 3-point star maze with 3 choice compartments containing: pups, a sexually active male, or no stimulus (neutral). Cycling maternal and nonmaternal females in late proestrus, independently of their previous reproductive experience, strongly preferred the male to the pups, although most postpartum estrous dams did not exhibit preference for the male. The majority of the postpartum primiparous females did not prefer the litter's chamber either, but a previous reproductive experience strongly determined their preference for the pups. These results suggest that the hormonal changes of the proestrus, in contrast to those of the postpartum estrus, promote a strong preference for the male that is not diminished by the maternal condition. Conversely, the endocrine changes of the postpartum facilitate the effect of previous reproductive experience in strengthening the incentive value of the pups.
Assuntos
Discriminação Psicológica/fisiologia , Comportamento Materno/fisiologia , Reprodução/fisiologia , Comportamento Sexual Animal/fisiologia , Olfato/fisiologia , Animais , Animais Recém-Nascidos , Comportamento Animal , Comportamento de Escolha/fisiologia , Feminino , Masculino , Motivação , Ratos , Ratos Wistar , Tempo de Reação/fisiologia , Estatísticas não ParamétricasRESUMO
The aim of the present study was to explore putative differences in the responses assessed in an animal model of obsessive-compulsive disorder (OCD) according to the sex and the reproductive cycle of female rats. The model consists of the induction of perseveration (repetitive choices of the same arm in a T-maze) by 8-OH-DPAT (1.0mg/kg). Males and females (pooled in all stages of their oestrous cycle) persevered after 8-OH-DPAT administration and no differences were observed between groups. During the oestrous cycle, this 5-HT(1A) agonist induced perseveration in metoestrus, dioestrus and prooestrus and reduced levels of this behaviour in oestrus. 8-OH-DPAT provoked perseveration in mid-gestation, an effect that was reduced in late-gestation and blocked during lactation. Reproductive cycle changes in the induced perseveration are discussed from the standpoint of the ovarian steroids' action on the serotoninergic system and on the bases of the variations in stress responsiveness along the reproductive cycle of the female. Present results validate the use of females in this model of OCD and could be relevant for studying the role of reproductive hormones in the pathophysiology of this disorder.
Assuntos
Comportamento Compulsivo/fisiopatologia , Ciclo Estral/fisiologia , Caracteres Sexuais , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Análise de Variância , Animais , Comportamento de Escolha/efeitos dos fármacos , Comportamento Compulsivo/induzido quimicamente , Comportamento Compulsivo/psicologia , Modelos Animais de Doenças , Feminino , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Agonistas do Receptor de Serotonina/farmacologia , Fatores SexuaisRESUMO
Although recent studies have provided a detailed understanding of cellular interactions occurring during the development of the CNS, little is known about the molecular signals which during the peri and postnatal periods ensure its maturation and functionality. Using the mammalian spinal cord as a model, we have designed experiments to examine the main changes in gene expression occurring during this critical transition. In this paper we describe the cloning and characterization of the rat hypoxia induced gene-1 (Hig-1), its expression pattern during spinal cord maturation and in situ localization of its mRNA. We show an increase in Hig-1 expression between P1 and P15 in the spinal cord and a differential spatial pattern. In the P1 spinal cord we observed preferential expression in regions of dorsal laminae II and III and laminae IX ventrally; while in P8, the distribution was more widespread and overall expression was increased. Hig-1 is also widely expressed in the brain. Results of in situ hybridization experiments, as well as particular features concerning ESTs, led us to propose the expression of an antisense mRNA. Primer-specific RTPCR demonstrates the presence of this aHig-1 transcript whose structure has not yet been characterized. The high homology between putative rHig-1 protein and human- and murine-predicted sequences, as well as its characteristic expression in the Central Nervous System, are indicative of a specific role which could be related to apoptosis signaling during postnatal maturation.
Assuntos
Regulação da Expressão Gênica , Hipóxia/genética , Proteínas de Neoplasias/genética , RNA Antissenso/metabolismo , Medula Espinal/metabolismo , Sequência de Aminoácidos , Animais , Animais Recém-Nascidos , Sequência de Bases , DNA Complementar , Humanos , Hipóxia/metabolismo , Hibridização In Situ , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas Mitocondriais , Dados de Sequência Molecular , Proteínas de Neoplasias/metabolismo , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de AminoácidosRESUMO
Luego del parto las ratas desarrollan conductas de cuidado de las crías y se vuelven agresivas ante congéneres intrusos. Las ratas vírgenes ovariectomizadas, luego de un tratamiento hormonal que simula los cambios endócrinos de la gestación y el parto y sometidas al contacto con crías neonatas, muestran comportamiento maternal y agresión ante intrusos. Este proceso se denomina sensibilización. El objetivo de este trabajo fue determinar si ratas vírgenes sensibilizadas sin tratamiento hormonal son agresivas frente a machos intrusos. Nuestros resultados mostraron que estos animales desarrollaron comportamiento maternal y aumentaron la agresión ante los intrusos en comparación con las ratas vírgenes ovariectomizadas no-maternales. Sin embargo, las madres lactantes fueron considerablemente más agresivas que las vírgenes sensibilizadas. Estos resultados sugieren que la agresión maternal podría asociarse al desarrollo del comportamiento maternal y no dependería exclusivamente de factores endócrinos [AU]