Glutamate and opioid antagonists modulate dopamine levels evoked by innately attractive male chemosignals in the nucleus accumbens of female rats

Sexual chemosignals detected by vomeronasal and olfactory systems mediate intersexual attraction in rodents, and act as a natural reinforcer to them. The mesolimbic pathway processes natural rewards, and the nucleus accumbens receives olfactory information via glutamatergic projections from the amygdala. Thus, the aim of this study was to investigate the involvement of the mesolimbic pathway in the attraction toward sexual chemosignals. Our data show that female rats with no previous experience with males or their chemosignals display an innate preference for male-soiled bedding. Focal administration of the opioid antagonist b-funaltrexamine into the posterior ventral tegmental area does no…

The maternal hormone in the male brain: Sexually dimorphic distribution of prolactin signalling in the mouse brain.

Research of the central actions of prolactin is highly focused on females, but this hormone has also documented roles in male physiology and behaviour. Here, we provide the first description of the pattern of prolactin-derived signalling in the male mouse brain, employing the immunostaining of phosphorylated signal transducer and activator of transcription 5 (pSTAT5) after exogenous prolactin administration. Next, we explore possible sexually dimorphic differences by comparing pSTAT5 immunoreactivity in prolactin-supplemented males and females. We also assess the role of testosterone in the regulation of central prolactin signalling in males by comparing intact with castrated prolactin-supp…

Intraspecific Communication Through Chemical Signals in Female Mice: Reinforcing Properties of Involatile Male Sexual Pheromones

In rodents, social and reproductive behaviors critically depend on chemical signals, including sexual pheromones that have been suggested (but not demonstrated) to be rewarding. In this work, we analyze this issue by studying the chemoinvestigatory behavior of adult female mice (without experience with male-derived chemicals) toward 1) the synthetic odorant citralva, 2) bedding soiled by different conspecifics (females, males, and castrated males), and 3) volatiles derived from bedding soiled by males and castrated males (confronted in 2-choice tests). We also study whether these chemical signals are able to induce conditioned place preference, a reliable test for rewarding properties of st…

Sexual pheromones and the evolution of the reward system of the brain: the chemosensory function of the amygdala.

The amygdala of all tetrapod vertebrates receives direct projections from the main and accessory olfactory bulbs, and the strong similarities in the organization of these projections suggest that they have undergone a very conservative evolution. However, current ideas about the function of the amygdala do not pay sufficient attention to its chemosensory role, but only view it as the core of the emotional brain. In this study, we propose that both roles of the amygdala are intimately linked since the amygdala is actually involved in mediating emotional responses to chemical signals. The amygdala is the only structure in the brain receiving pheromonal information directly from the accessory …

Pregnancy Changes the Response of the Vomeronasal and Olfactory Systems to Pups in Mice

Motherhood entails changes in behavior with increased motivation for pups, induced in part by pregnancy hormones acting upon the brain. This work explores whether this alters sensory processing of pup-derived chemosignals. To do so, we analyse the expression of immediate early genes (IEGs) in the vomeronasal organ (VNO; Egr1) and centers of the olfactory and vomeronasal brain pathways (cFos) in virgin and late-pregnant females exposed to pups, as compared to buttons (socially neutral control). In pup-exposed females, we quantified diverse behaviors including pup retrieval, sniffing, pup-directed attack, nest building and time in nest or on nest, as well as time off nest. Pups induce Egr1 ex…

Avoidance and contextual learning induced by a kairomone, a pheromone and a common odorant in female CD1 mice

Copyright © 2015 Fortes-Marco, Lanuza, Martínez-García and Agustín-Pavón.

MeCP2 haplodeficiency and early-life stress interaction on anxiety-like behavior in adolescent female mice

Abstract Background Early-life stress can leave persistent epigenetic marks that may modulate vulnerability to psychiatric conditions later in life, including anxiety, depression and stress-related disorders. These are complex disorders with both environmental and genetic influences contributing to their etiology. Methyl-CpG Binding Protein 2 (MeCP2) has been attributed a key role in the control of neuronal activity-dependent gene expression and is a master regulator of experience-dependent epigenetic programming. Moreover, mutations in the MECP2 gene are the primary cause of Rett syndrome and, to a lesser extent, of a range of other major neurodevelopmental disorders. Here, we aim to study…

Role of the vomeronasal system in intersexual attraction in female mice

Although it is generally accepted that rodents' sociosexual behavior relies mainly on chemosignals, the specific roles played by the vomeronasal and olfactory systems in detecting these signals are presently unclear. This work reports the results of three experiments aimed at clarifying the role of the vomeronasal system on gender recognition and intersexual attraction, by analyzing the effects of lesions of the accessory olfactory bulbs (AOB) in chemically naive female mice. The first experiment demonstrates that lesions of the AOB abolish the preference that females show for male-soiled bedding in tests in which the females can contact the bedding, thus having access to both volatile and …

Refining the dual olfactory hypothesis: Pheromone reward and odour experience

In rodents, sexual advertisement and gender recognition are mostly (if not exclusively) mediated by chemosignals. Specifically, there is ample evidence indicating that female mice are ‘innately’ attracted by male sexual pheromones that have critical non-volatile components and are detected by the vomeronasal organ. These pheromones can only get access to the vomeronasal organ by active pumping mechanisms that require close contact with the source of the stimulus (e.g. urine marks) during chemoinvestigation. We have hypothesised that male sexual pheromones are rewarding to female mice. Indeed, male-soiled bedding can be used as a reinforcer to induce conditioned place preference, provided co…

Focal Lesions within the ventral striato-pallidum abolish attraction for male chemosignals in female mice

In rodents, socio-sexual behaviour is largely mediated by chemosensory cues, some of which are rewarding stimuli. Female mice display an innate attraction towards male chemosignals, dependent on the vomeronasal system. This behaviour likely reflects the hedonic value of sexual chemosignals. The anteromedial aspect of the olfactory tubercle, along with its associated islands of Calleja, receives vomeronasal inputs and sexually-dimorphic vasopressinergic innervation. Thus, we hypothesised that this portion of the ventral striato-pallidum, known to be involved in reward processing, might be important for sexual odorant-guided behaviours. In this study, we demonstrate that lesions of this regio…

Activation of MORs in the VTA induces changes on cFos expression in different projecting regions: Effect of inflammatory pain.

Abstract Chronic pain is a worldwide major health problem and many pain-suffering patients are under opioid based therapy. Epidemiological data show that pain intensity correlates with the risk of misuse of prescription opioids, and other drugs of abuse including alcohol. This increased vulnerability to suffer Substance Use Disorders could be, in part, caused by functional changes that occur over the mesocorticolimbic system, a brain pathway involved in reward processing and addiction. Previous data in rats revealed that inflammatory pain desensitizes mu opioid receptors (MORs) in the ventral tegmental area (VTA). As a consequence, pain alters dopamine release in the nucleus accumbens (NAc)…

Corrigendum: Wired for motherhood: induction of maternal care but not maternal aggression in virgin female CD1 mice

Crosstalk between Mu-Opioid receptors and neuroinflammation: Consequences for drug addiction and pain

Mu-Opioid Receptors (MORs) are well-known for participating in analgesia, sedation, drug addiction, and other physiological functions. Although MORs have been related to neuroinflammation their biological mechanism remains unclear. It is suggested that MORs work alongside Toll-Like Receptors to enhance the release of pro-inflammatory mediators and cytokines during pathological conditions. Some cytokines, including TNF-α, IL-1β and IL-6, have been postulated to regulate MORs levels by both avoiding MOR recycling and enhancing its production. In addition, Neurokinin-1 Receptor, also affected during neuroinflammation, could be regulating MOR trafficking. Therefore, inflammation in the central …

Maternal Motivation: Exploring the Roles of Prolactin and Pup Stimuli

Motherhood entails increased motivation for pups, which become strong reinforcers and guide maternal behaviours. This depends on steroids and lactogens acting on the brain of females during pregnancy and postpartum. Since virgin female mice exposed to pups are nearly spontaneously maternal, the specific roles of endocrine and pup-derived signals in the induction of maternal motivation remain unclear. This work investigates maternal motivation in dams and virgin female mice, using a novel variant of the pup retrieval paradigm, the motivated pup retrieval test. We also analyse the role of prolactin (PRL) and of stimuli derived from a litter of pups and its mother, in the acquisition of matern…

Neuroquímica del refuerzo inducido por feromonas.

RESUMEN Las feromonas sexuales masculinas atraen a de manera innata a las hembras de ratón. Estos estímulos no sólo son explorados intensa y preferentemente por las hembras sino que inducen preferencia condicionada de lugar (PCL), lo cual constituye una prueba de que la detección de las feromonas de macho es una recompensa para las hembras. Así pues, la utilización de feromonas sexuales proporciona un modelo novedoso para para el estudio de los mecanismos y las bases neurales de los procesos de refuerzo. En la tesis doctoral Neuroquímica del refuerzo inducido por feromonas se pretendió explorar cuales son los neurotransmisores que regulan el comportamiento de atracción innata por feromonas …

Motherhood‐induced gene expression in the mouse medial amygdala: Changes induced by pregnancy and lactation but not by pup stimuli

During lactation, adult female mice display aggressive responses toward male intrud-ers, triggered by male- derived chemosensory signals. This aggressive behavior is not shown by pup- sensitized virgin females sharing pup care with dams. The genetic mechanisms underlying the switch from attraction to aggression are unknown. In this work, we investigate the differential gene expression in lactating females ex-pressing maternal aggression compared to pup- sensitized virgin females in the me-dial amygdala (Me), a key neural structure integrating chemosensory and hormonal information. The results showed 197 genes upregulated in dams, including genes encoding hormones such as prolactin, growth h…

Distinct patterns of Fos immunoreactivity in striatum and hippocampus induced by different kinds of novelty in mice.

In this study the immediate-early gene Fos was used to investigate the response to different novel stimuli in a wide array of brain regions including the hippocampus, the rhinal cortex, the frontal cortex and different components of the striatal complex. Independent groups of CD-1 mice were exposed to three different novelty conditions: (1) novel environment (empty open field); (2) complex novel environment (i.e. open field containing objects); and (3) identity-based detection of novel objects. We observed that a complex novel environment and a knowledge-based novelty modulated Fos levels in both the dorsal and the ventral components of the striatum, while Fos immunoreactivity in the medial…

Corrigendum: Wired for motherhood: induction of maternal care but not maternal aggression in virgin female CD1 mice

Virgin adult female mice display nearly spontaneous maternal care towards foster pups after a short period of sensitization. This indicates that maternal care is triggered by sensory stimulation provided by the pups and that its onset is largely independent on the physiological events related to gestation, parturition and lactation. Conversely, the factors influencing maternal aggression are poorly understood. In this study, we sought to characterize two models of maternal sensitization in the outbred CD1 strain. To do so, a group of virgin females (godmothers) were exposed to continuous cohabitation with a lactating dam and their pups from the moment of parturition, whereas a second group …

Role of nitric oxide in pheromone-mediated intraspecific communication in mice

Nitric oxide is known to take part in the control of sexual and agonistic behaviours. This is usually attributed to its role in neural transmission in the hypothalamus and other structures of the limbic system. However, socio-sexual behaviours in rodents are mainly directed by chemical signals detected by the vomeronasal system, and nitric oxide is abundant in key structures along the vomeronasal pathway. Thus, here we check whether pharmacological treatments interfering with nitrergic transmission could affect socio-sexual behaviour by impairing the processing of chemical signals. Treatment with an inhibitor of nitric oxide synthesis (Nomega-Nitro-l-arginine methyl ester hydrochloride, L-N…