Nathalie Jérôme

Proerectile effects of apomorphine in mice.

Dopaminergic pathways play a key role in the central control of sexual behavior. Stimulation of central dopaminergic receptors elicits penile erection in a variety of species and has been proposed as a treatment option for erectile dysfunction in humans. The present study investigated the proerectile effects of apomorphine in mice. In this species, subcutaneous injection of apomorphine (range: 0.11-110 microg/kg sc) elicited three different behavioral responses: erection, erection-like responses and genital grooming. Proerectile effects of apomorphine were dose-dependent. More than 50% of mice displayed erections after administration of 1.1-11 microg/kg of apomorphine sc. Proerectile effects of apomorphine were blocked by haloperidol, a central D2 antagonist, but not by domperidone, a peripherally active dopaminergic antagonist. We conclude that apomorphine elicits erection in mice. This effect is dose-dependent and due to activation of central D2 dopaminergic receptors. The mouse model may be useful for pharmacological approaches designed to provide a better understanding of the central mechanisms of penile erection and sexual behavior.

A mixture of odorant molecules potentially indicating oestrus in mammals elicits penile erections in male rats.

A common set of odorous molecules may indicate female receptiveness across species, as male rats display sexual arousal when exposed to the odour of oestrous faeces from rats, vixens and mares. More than 900 different compounds were identified by GC-MS analyses performed on faeces samples from di-oestrous and oestrous females and from males of the three species. Five carboxylic acids were found in lower concentrations in faeces from all oestrous females. We subjected 12 sexually trained male rats to a 30 min exposure to different dilutions of a mixture of these five molecules in the same proportions as found in female oestrous faeces. The behavioural responses of the rats were compared to those displayed when exposed to water (negative control) and faeces from oestrous female rats (positive control). Frequency of penile erections were found to be significantly dependent on mixture dilution, with two intermediate dilutions eliciting frequencies of penile erections that did not differ from those obtained during exposure to oestrous female rat faeces. Higher and lower dilutions did not elicit more penile erections than observed with water. These results support our hypothesis that a small set of odorous molecules may indicate sexual receptiveness in mammalian females.

Behavioural response of sexually naïve and experienced male rats to the smell of 6-methyl-5-hepten-2-one and female rat faeces

Sexually experienced male rats display penile erections when exposed to faeces from mammalian females in oestrus (Rampin et al., Behav Brain Res, 172:169, 2006), suggesting that specific odours indicate female receptiveness across species. However, it is unknown to what extent the sexual response observed results from an odorous conditioning acquired during sexual experience. We tested the behavioural response of male Brown Norway rats both when sexually naïve and experienced to four odours, including oestrous rat faeces and 6-methyl-5-hepten-2-one (methylheptenone; a molecule found in higher concentrations during oestrus in female rats, foxes and horses). Odour had a significant effect on the sexual response of the naïve rats, with oestrus faeces provoking significantly more erections than herb odour, and with methylheptenone and di-oestrus faeces being intermediate. This indicates that sexually naïve male rats have an unconditioned ability to detect oestrous mediated via odour. After gaining sexual experience, the response to methylheptenone, di- and oestrus faeces was significantly higher than that observed with herb odour. These results strongly suggest that methylheptenone is part of the odorous bouquet of oestrus and contributes to the olfactory determination of female receptiveness.

Are oestrus odours species specific

Adult male rats were exposed to faeces odours of three animal species (rat, fox and horse). They displayed erections in the presence of faeces from oestrous females (whatever the species). In addition, fox faeces (whatever the gender or hormonal status) elicited an expected freezing reaction. It is suggested that oestrous female faeces of these three species share common odorants which depend on the hormonal status and characterize female receptivity.

Brain processing of biologically relevant odors in the awake rat, as revealed by manganese-enhanced MRI.

Background So far, an overall view of olfactory structures activated by natural biologically relevant odors in the awake rat is not available. Manganese-enhanced MRI (MEMRI) is appropriate for this purpose. While MEMRI has been used for anatomical labeling of olfactory pathways, functional imaging analyses have not yet been performed beyond the olfactory bulb. Here, we have used MEMRI for functional imaging of rat central olfactory structures and for comparing activation maps obtained with odors conveying different biological messages. Methodology/Principal Findings Odors of male fox feces and of chocolate flavored cereals were used to stimulate conscious rats previously treated by intranasal instillation of manganese (Mn). MEMRI activation maps showed Mn enhancement all along the primary olfactory cortex. Mn enhancement elicited by male fox feces odor and to a lesser extent that elicited by chocolate odor, differed from that elicited by deodorized air. This result was partly confirmed by c-Fos immunohistochemistry in the piriform cortex. Conclusion/Significance By providing an overall image of brain structures activated in awake rats by odorous stimulation, and by showing that Mn enhancement is differently sensitive to different stimulating odors, the present results demonstrate the interest of MEMRI for functional studies of olfaction in the primary olfactory cortex of laboratory small animals, under conditions close to natural perception. Finally, the factors that may cause the variability of the MEMRI signal in response to different odor are discussed.

Sexual responses of male rats to odours from female rats in oestrus are not affected by female germ-free status

HighlightsGC–MS analysis was performed on faeces samples from germ‐free and conventional rats.Faeces from germ‐free rats contain fewer molecules and in lower abundance.Conventional rats have more penile erections when exposed to rat oestrous faeces.This was independent of the germ‐free status of the female.Thus, oestrous odours in rats appear not to be of microbial origin. Abstract Rats detect and use odorant molecules as a source of information about their environment. Some of these molecules come from conspecifics, and many arise as by‐products from microbial activity. Thus, compared to conventionally housed rats, germ‐free rats are raised in an environment with fewer odorants, but this reduction is rarely quantified. Using gas chromatography–mass spectrometry, we found that germ‐free rat faeces samples contained half as many volatile molecules than conventional rat faeces (52 vs 109 (±2.4) molecules; P < 0.001) and overall these were only 12% as abundant. We then investigated if odours from female germ‐free rats in oestrus would have pro‐erectile effects in conventional male rats. For this aim, conventionally housed Brown Norway (BN) rats (n = 16) with sexual experience with either Fischer or BN females, were exposed to four different odour types: faeces from germ‐free Fischer rat in oestrus, faeces from conventional rats in oestrus and di‐oestrus (either from Fischer or BN), and a control (either 1‐hexanol or male rat faeces). The number of penile erections per test as well as the duration of freezing behaviour was significantly higher with the oestrous odours (germ‐free and conventional) compared to the control, with intermediate responses to the di‐oestrous faeces. The findings indicate that, despite a significantly reduced composition in terms of volatiles compared to conventionally housed rats, the faeces of germ‐free rats contain sufficient odorants to evoke sexual responses in conventional male rats. Oestrous odours of rats thus appear not to be of microbial origin.

Central Processing of Behaviorally Relevant Odors in the Brain of Awake Rats, as Revealed by Functional Manganese-enhanced MRI

An overall view of olfactory structures activated by biologically relevant odors in conscious rats has not been available up to now. Manganese (Mn)-enhanced MRI (MEMRI) could be an appropriate method to provide such a view because it is based on the detection of Mn, a persistent intra-cellular functional contrast agent. Whereas MEMRI has been used for anatomical labeling of olfactory pathways, functional imaging analyses have not yet been performed beyond the olfactory bulb. Here, we have used MEMRI for the functional imaging of rat central olfactory structures and for comparing activation maps obtained with odors conveying different biological messages. The odors used were those of male fox feces, that triggers an innate fear reaction, and of chocolate-flavored cereals, that is linked to a food reward. They were used to stimulate conscious rats previously treated by intranasal instillation of Mn at a dose optimized to ensure reproducible contrast in MR images of whole brain at 4.7 T, while sparing olfactory perception. MEMRI activation maps showed Mn enhancement throughout the primary olfactory cortex. Mn enhancement elicited by fox odor differed from that elicited by deodorized air (used as a control), whereas Mn enhancement elicited by chocolate odor did not. By providing an overall image of brain structures activated in conscious rats by odorous stimulation, these results demonstrate the interest of MEMRI for functional studies of olfaction in small laboratory animals. Our results also suggest that the activation of deep brain olfactory structures depends on the biological significance of the odorous message.