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1.
Front Behav Neurosci ; 17: 1089631, 2023.
Article in English | MEDLINE | ID: mdl-36815182

ABSTRACT

Rats produce ultrasonic vocalisation (USVs) that are classified into different types, based on their average frequency. In pups 40 kHz USVs are produced upon social isolation, and in adults USVs can be associated with affective states and specific behavioural patterns (i.e., appetitive 50 kHz vocalisations of frequency range 30-100 kHz, or aversive 20 kHz vocalisations of frequency range 18-30 kHz). Generally, USVs of frequency around 50 kHz are linked to activation of brain reward pathways, during anticipation or experience of rewarding stimuli. Previous studies have described several subtypes of 50 kHz USVs, according to their acoustic properties. We asked whether USV production might be relevant to feeding behaviour. We recorded USVs from 14-week old adult rats during the satisfaction of a physiological need: refeeding following mild food deprivation (17 h overnight fast). We analysed a 10 min consummatory phase, preceded by a 10 min anticipatory phase, as a control for the experimental meal. Following identification of USV subtypes, we applied frequentist and Bayesian (Monte Carlo shuffling) statistical analyses to investigate the relationship between USV emission and rat behaviour. We found that it was not total USV quantity that varied in response to food consumption, but the subtype of USV produced. Most importantly we found that rats who feed tend to produce flat USVs of a frequency around 40 kHz. Beyond the previous reports of circumstantial association feeding-flat USVs, our observation directly correlate vocalisation and ingestive behaviour. Our study highlights that, in addition to quantification of the production rate, study of USV subtypes might inform us further on rat consummatory behaviour. Since this vocalisation behaviour can have a communicative purpose, those findings also illustrate nutrition studies might benefit from considering the possible social dimension of feeding behaviour.

2.
Biomedicines ; 10(5)2022 May 12.
Article in English | MEDLINE | ID: mdl-35625863

ABSTRACT

Food odour is a potent stimulus of food intake. Odour coding in the brain occurs in synergy or competition with other sensory information and internal signals. For eliciting feeding behaviour, food odour coding has to gain signification through enrichment with additional labelling in the brain. Since the ventral striatum, at the crossroads of olfactory and reward pathways, receives a rich dopaminergic innervation, we hypothesized that dopamine plays a role in food odour information processing in the ventral striatum. Using single neurones recordings in anesthetised rats, we show that some ventral striatum neurones respond to food odour. This neuronal network displays a variety of responses (excitation, inhibition, rhythmic activity in phase with respiration). The localization of recorded neurones in a 3-dimensional brain model suggests the spatial segregation of this food-odour responsive population. Using local field potentials recordings, we found that the neural population response to food odour was characterized by an increase of power in the beta-band frequency. This response was modulated by dopamine, as evidenced by its depression following administration of the dopaminergic D1 and D2 antagonists SCH23390 and raclopride. Our results suggest that dopamine improves food odour processing in the ventral striatum.

3.
J Nutr ; 151(5): 1311-1319, 2021 05 11.
Article in English | MEDLINE | ID: mdl-33693927

ABSTRACT

BACKGROUND: A low-protein diet can induce compensatory intake of excess energy. This must be better evaluated to anticipate the obesogenic risk that may result from the dietary recommendations for reducing animal protein consumption. OBJECTIVES: We aimed to further characterize the behavioral and physiological responses to a reduction in dietary protein and to identify the determinants of protein appetite. METHODS: Thirty-two male Wistar rats [4 wk old, (mean ± SEM) 135 ± 32 g body weight] were fed a low-protein (LP; 6% energy value) or normal-protein (NP; 20%) diet for 8 wk. Food intake and body mass were measured during the entire intervention. During self-selection sessions after 4 wk of experimental diets, we evaluated rat food preference between LP, NP, or high-protein (HP; 55%) pellets. At the end of the experiment, we assessed their hedonic response [ultrasonic vocalizations (USVs)] and c-Fos neuronal activation in the olfactory tubercle and nucleus accumbens (NAcc) associated with an LP or HP meal. RESULTS: Rats fed an LP diet had greater food intake (24%), body weight (5%), and visceral adiposity (30%) than NP rats. All LP rats and half of the NP rats showed a nearly exclusive preference for HP pellets during self-selection sessions, whereas the other half of the NP rats showed no preference. This suggests that the appetite for proteins is driven not only by a low protein status but also by individual traits in NP rats. LP or HP meal induced similar USV emission and similar neuronal activation in the NAcc in feed-deprived LP and NP rats, showing no specific response linked to protein appetite. CONCLUSIONS: Protein appetite in rats is driven by low protein status or individual preferences in rats receiving adequate protein amounts. This must be considered and further analyzed, in the context of current recommendations for protein intake reduction.


Subject(s)
Appetite/drug effects , Diet, Protein-Restricted , Dietary Proteins/pharmacology , Eating/drug effects , Energy Intake/drug effects , Food Preferences/drug effects , Phenotype , Adiposity , Animals , Body Weight , Dietary Proteins/administration & dosage , Intra-Abdominal Fat , Male , Meat , Nucleus Accumbens , Obesity , Olfactory Tubercle , Rats, Wistar
4.
Brain Behav Immun ; 89: 579-586, 2020 10.
Article in English | MEDLINE | ID: mdl-32629042

ABSTRACT

Anosmia is one of the most prevalent symptoms of SARS-CoV-2 infection during the COVID-19 pandemic. However, the cellular mechanism behind the sudden loss of smell has not yet been investigated. The initial step of odour detection takes place in the pseudostratified olfactory epithelium (OE) mainly composed of olfactory sensory neurons surrounded by supporting cells known as sustentacular cells. The olfactory neurons project their axons to the olfactory bulb in the central nervous system offering a potential pathway for pathogens to enter the central nervous system by bypassing the blood brain barrier. In the present study, we explored the impact of SARS-CoV-2 infection on the olfactory system in golden Syrian hamsters. We observed massive damage of the OE as early as 2 days post nasal instillation of SARS-CoV-2, resulting in a major loss of cilia necessary for odour detection. These damages were associated with infection of a large proportion of sustentacular cells but not of olfactory neurons, and we did not detect any presence of the virus in the olfactory bulbs. We observed massive infiltration of immune cells in the OE and lamina propria of infected animals, which may contribute to the desquamation of the OE. The OE was partially restored 14 days post infection. Anosmia observed in COVID-19 patient is therefore likely to be linked to a massive and fast desquamation of the OE following sustentacular cells infection with SARS-CoV-2 and subsequent recruitment of immune cells in the OE and lamina propria.


Subject(s)
Coronavirus Infections/pathology , Olfactory Bulb/pathology , Olfactory Mucosa/pathology , Pneumonia, Viral/pathology , Animals , Betacoronavirus , COVID-19 , Cilia/pathology , Coronavirus Infections/physiopathology , Mesocricetus , Olfaction Disorders/pathology , Olfaction Disorders/physiopathology , Olfactory Bulb/virology , Olfactory Mucosa/virology , Olfactory Receptor Neurons/pathology , Olfactory Receptor Neurons/virology , Pandemics , Pneumonia, Viral/physiopathology , SARS-CoV-2
5.
Behav Brain Res ; 362: 1-6, 2019 04 19.
Article in English | MEDLINE | ID: mdl-30597250

ABSTRACT

In the olfactory epithelium, olfactory sensitive neurons and their axons are surrounded by glia-like cells called sustentacular cells, which maintain both the structural and ionic integrity of the olfactory mucosa. We have previously found that endothelin-1 (ET-1) can uncouple sustentacular cell gap junctions in vitro similarly as carbenoxolone, a known gap junction uncoupling agent. The role of gap junctions in odorant transduction remains controversial and we explored here if ET-1 naturally produced by the olfactory mucosa could impact odorant detection. Using calcium imaging on olfactory mucosa explant, we first confirmed that ET-1 uncouples gap junctions in an olfactory mucosa preparation preserving the tissue integrity. We next measured the olfactory epithelium responses to odorant stimulation using electro-olfactogram recordings. While the amplitude of the response was not modified by application of ET-1 and carbenoxolone, its repolarizing phase was slower after both treatments. We finally examined the behavioral performances of rat pups in an orientation test based on maternal odor recognition after intranasal instillations of ET-1 or carbenoxolone. While rat pups performances were decreased after ET-1 treatment, it was unchanged after carbenoxolone treatment. Overall, our results indicate that ET-1 modulates olfactory responses at least partly through gap junction uncoupling.


Subject(s)
Behavior, Animal/drug effects , Endothelin-1/pharmacology , Olfactory Mucosa/drug effects , Smell/drug effects , Animals , Animals, Newborn , Calcium/metabolism , Male , Neuroglia/drug effects , Neurons/drug effects , Odorants , Olfactory Mucosa/physiology , Rats, Wistar , Smell/physiology
6.
Chem Senses ; 43(2): 105-115, 2018 02 02.
Article in English | MEDLINE | ID: mdl-29228118

ABSTRACT

TMT (2,5-dihydro-2,4,5-trimethylthiazoline) is known as a component of fox feces inducing fear in rodents. However, no recent chemical analyses of fox feces are available, and few studies make direct comparisons between TMT and fox feces. Fox feces from 3 individuals were used to prepare 24 samples to be analyzed for the presence of TMT using gas chromatography-mass spectrometry (GC-MS). When TMT was added in low amounts (50-2000 nmol/g), TMT was detected in 10 out of 11 samples. When no TMT was added, TMT was detected in only 1 out of 13 samples. In a second experiment, we tested the behavioral response of male Brown Norway (BN) and Wistar rats to either fox feces, a low amount of TMT (0.6 nmol) or 1-hexanol. TMT induced freezing in the rats, but fox feces induced significantly more freezing episodes and longer total duration of freezing in both rat strains. In experiment 3, male BN rats were exposed over several days to fox feces, rat feces, 1-hexanol, cadaverine, 2-phenylethylamine, and TMT, one odor at a time. Fox feces induced significantly more freezing episodes of a longer total duration than any of the other odors, with rat feces and 1-hexanol giving rise to the lowest amount of freezing. This finding, together with our inability to verify the presence of TMT in fox feces, indicates that the concentration of TMT in our fox feces samples was below 50 nmol/g. It may also be that other compounds in fox feces play a role in its fear-inducing properties.


Subject(s)
Behavior, Animal/physiology , Fear/physiology , Feces/chemistry , Foxes/physiology , Gas Chromatography-Mass Spectrometry/methods , Odorants , Rats/psychology , Thiazoles/analysis , Animals , Freezing Reaction, Cataleptic , Male , Rats, Wistar , Species Specificity
7.
Front Neurosci ; 9: 226, 2015.
Article in English | MEDLINE | ID: mdl-26161069

ABSTRACT

It has long been known that the behavior of an animal can be affected by odors from another species. Such interspecific effects of odorous compounds (allelochemics) are usually characterized according to who benefits (emitter, receiver, or both) and the odors categorized accordingly (allomones, kairomones, and synomones, respectively), which has its origin in the definition of pheromones, i.e., intraspecific communication via volatile compounds. When considering vertebrates, however, interspecific odor-based effects exist which do not fit well in this paradigm. Three aspects in particular do not encompass all interspecific semiochemical effects: one relates to the innateness of the behavioral response, another to the origin of the odor, and the third to the intent of the message. In this review we focus on vertebrates, and present examples of behavioral responses of animals to odors from other species with specific reference to these three aspects. Searching for a more useful classification of allelochemical effects we examine the relationship between the valence of odors (attractive through to aversive), and the relative contributions of learned and unconditioned (innate) behavioral responses to odors from other species. We propose that these two factors (odor valence and learning) may offer an alternative way to describe the nature of interspecific olfactory effects involving vertebrates compared to the current focus on who benefits.

8.
Physiol Behav ; 120: 150-5, 2013 Aug 15.
Article in English | MEDLINE | ID: mdl-23911690

ABSTRACT

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.


Subject(s)
Behavior, Animal/physiology , Feces/chemistry , Ketones/pharmacology , Sexual Behavior, Animal/drug effects , Smell/physiology , Animals , Diestrus/physiology , Estrus/physiology , Female , Male , Odorants , Penile Erection/physiology , Rats , Rats, Inbred BN
9.
PLoS One ; 7(10): e48491, 2012.
Article in English | MEDLINE | ID: mdl-23119035

ABSTRACT

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.


Subject(s)
Brain/physiology , Magnetic Resonance Imaging , Manganese , Odorants , Olfactory Perception/physiology , Animals , Image Enhancement , Male , Olfactory Pathways/diagnostic imaging , Olfactory Pathways/physiology , Proto-Oncogene Proteins c-fos/metabolism , Radionuclide Imaging , Rats
10.
Eur J Neurosci ; 35(1): 97-105, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22118424

ABSTRACT

Biologically relevant odours were used to stimulate olfactory tubercle neurons in anaesthetized male rats. Among 120 recorded neurons, 118 showed spontaneous activity (mean firing rate, 15.0 ± 1.4 spikes/s). Ninety-eight neurons were exposed to at least one of the four following odour sources: an empty vial, or a vial containing food pellets (familiar odour), a sample of oestrous rat faeces (conspecific sexual odour), or a sample of male fox faeces (predator odour). The proportion of neurons responding with a change in activity was significantly linked to the odour applied. Repetition of the stimulation with the same odour elicited the same activity change. Between 50 and 70% of neuronal activity changes were not accompanied by respiration changes. Fifty-six neurons were exposed successively to all four odours, and 38 of them showed an activity change in response to at least one. The response of a neuron to an odour was not affected by its response to the previous one, and no neuron responded in the same manner to all odours. Conversely, no odour elicited a unique response in this population of neurons. However, the proportions of excited, inhibited and insensitive neurons depended significantly on the odour applied, suggesting that the recruitment of olfactory tubercle neurons is directly dependent on the biological significance of the odour.


Subject(s)
Action Potentials/physiology , Neurons/physiology , Odorants , Olfactory Pathways/cytology , Animals , Electrophysiology , Male , Neurons/cytology , Olfactory Pathways/physiology , Rats , Stimulation, Chemical
11.
Behav Brain Res ; 225(2): 584-9, 2011 Dec 01.
Article in English | MEDLINE | ID: mdl-21884731

ABSTRACT

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.


Subject(s)
Carboxylic Acids/analysis , Estrus/physiology , Feces/chemistry , Penile Erection/physiology , Sexual Behavior, Animal/physiology , Administration, Inhalation , Animals , Carboxylic Acids/administration & dosage , Female , Foxes , Horses , Male , Odorants , Penile Erection/drug effects , Rats , Sexual Behavior, Animal/drug effects
12.
PLoS One ; 5(2): e8974, 2010 Feb 01.
Article in English | MEDLINE | ID: mdl-20126542

ABSTRACT

BACKGROUND: The caudal brainstem plays an important role in short-term satiation and in the control of meal termination. Meal-related stimuli sensed by the gastrointestinal (GI) tract are transmitted to the area postrema (AP) via the bloodstream, or to the nucleus tractus solitarii (NTS) via the vagus nerve. Little is known about the encoding of macronutrient-specific signals in the caudal brainstem. We hypothesized that sucrose and casein peptone activate spatially distinct sub-populations of NTS neurons and thus characterized the latter using statistical three-dimensional modeling. METHODOLOGY/PRINCIPAL FINDINGS: Using immunolabeling of the proto-oncogene Fos as a marker of neuronal activity, in combination with a statistical three-dimensional modeling approach, we have shown that NTS neurons activated by sucrose or peptone gavage occupy distinct, although partially overlapping, positions. Specifically, when compared to their homologues in peptone-treated mice, three-dimensional models calculated from neuronal density maps following sucrose gavage showed that Fos-positive neurons occupy a more lateral position at the rostral end of the NTS, and a more dorsal position at the caudal end. CONCLUSION/SIGNIFICANCE: To our knowledge, this is the first time that subpopulations of NTS neurons have be distinguished according to the spatial organization of their functional response. Such neuronal activity patterns may be of particular relevance to understanding the mechanisms that support the central encoding of signals related to the presence of macronutrients in the GI tract during digestion. Finally, this finding also illustrates the usefulness of statistical three-dimensional modeling to functional neuroanatomical studies.


Subject(s)
Brain Stem/anatomy & histology , Brain Stem/metabolism , Models, Anatomic , Proto-Oncogene Proteins c-fos/biosynthesis , Animals , Brain Stem/cytology , Caseins/administration & dosage , Dietary Proteins/administration & dosage , Dietary Sucrose/administration & dosage , Immunohistochemistry , Male , Mice , Mice, Inbred C57BL , Neurons/cytology , Neurons/drug effects , Neurons/metabolism , Solitary Nucleus/anatomy & histology , Solitary Nucleus/cytology , Solitary Nucleus/metabolism , Sucrose/administration & dosage
13.
J Comp Neurol ; 513(5): 483-95, 2009 Apr 10.
Article in English | MEDLINE | ID: mdl-19226531

ABSTRACT

An algorithm for the three-dimensional statistical representation of neuronal populations was designed and implemented. Using this algorithm a series of 3D models, calculated from repeated histological experiments, can be combined to provide a synthetic vision of a population of neurons taking into account biological and experimental variability. Based on the point process theory, our algorithm allows computation of neuronal density maps from which isodensity surfaces can be readily extracted and visualized as surface models revealing the statistical organization of the neuronal population under study. This algorithm was applied to the spatial distribution of locus coeruleus (LC) neurons of 30- and 90-day-old control and quaking mice. By combining 12 3D models of the LC, a region of the nucleus in which a subpopulation of neurons loses its noradrenergic phenotype between 30 and 90 days postnatally was demonstrated in control mice but not in quaking mice, leading to the hyperplasia previously reported in adult mutants. Altogether, this algorithm allows computation of 3D statistical and graphical models of neuronal populations, providing a contribution to quantitative 3D neuroanatomical modeling.


Subject(s)
Algorithms , Imaging, Three-Dimensional/methods , Locus Coeruleus/anatomy & histology , Neurons/metabolism , Tyrosine 3-Monooxygenase/metabolism , Age Factors , Animals , Cell Count , Locus Coeruleus/cytology , Locus Coeruleus/enzymology , Mice , Mice, Quaking , Models, Statistical
14.
Behav Brain Res ; 172(1): 169-72, 2006 Sep 15.
Article in English | MEDLINE | ID: mdl-16740322

ABSTRACT

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.


Subject(s)
Estrus/physiology , Odorants , Animals , Cues , Feces/chemistry , Female , Foxes , Horses , Male , Penile Erection/physiology , Rats , Rats, Inbred BN , Sexual Behavior, Animal/physiology , Species Specificity
15.
Cell Tissue Res ; 323(3): 359-75, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16307288

ABSTRACT

In male rats, the dorsal penile nerve (DPN) conveys sensory information from the genitals to the lumbosacral spinal segments of the spinal cord. DPN is the afferent limb of a reflex loop that supports reflexive erections, and that includes a network of spinal interneurons and autonomic and somatic motoneurons to the penis and perineal striated muscles. Autonomic efferent pathways to the penis relay in the major pelvic ganglion (MPG). Glutamate (Glu) is a likely candidate as a neurotransmitter of reflexive erections. Both AMPA and NMDA glutamatergic receptor subunits are present in the lumbosacral spinal cord, and AMPA and NMDA receptor antagonists block reflexive erections. In the present study, we used tract-tracing experiments combined with immunohistochemical and immunocytochemical techniques to ascertain the presence of Glu at two different levels of the network controlling reflexive erections. DPN afferents were localized in the dorsal horn of the lumbosacral cord and displayed the characteristics of either C-fibers or Adelta fibers. DPN terminals (some of them glutamatergic) were mainly distributed in the medial edge of the dorsal horn in the L6 spinal segment. GluR1 subunits were present in some DPN afferents, suggesting that they could be autoreceptors. DPN fibers were also present in the MPG, as were Glu terminals and GluR4 subunits. The results reveal the presence of Glu in DPN fibers and terminals and suggest that both the spinal cord and the MPG use glutamatergic transmission to control reflexive erections.


Subject(s)
Glutamic Acid/metabolism , Neurons, Afferent/physiology , Penile Erection/physiology , Penis/innervation , Spinal Cord/physiology , Synaptic Transmission , Animals , Ganglia, Spinal/drug effects , Ganglia, Spinal/physiology , Ganglia, Spinal/ultrastructure , Immunohistochemistry , Lumbosacral Region , Male , Microscopy, Electron, Transmission , N-Methylaspartate/pharmacology , Nerve Fibers/metabolism , Neurons, Afferent/ultrastructure , Penile Erection/drug effects , Rats , Rats, Sprague-Dawley , Receptors, AMPA/agonists , Receptors, AMPA/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/agonists , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Spinal Cord/cytology , Spinal Cord/ultrastructure , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology
16.
Am J Physiol Regul Integr Comp Physiol ; 289(3): R798-804, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16105822

ABSTRACT

The central nervous system contains the nuclei at the origin of autonomic and neuroendocrine pathways to the uterus. Although the anatomical basis of these pathways is known, the conditions of their recruitment and their interactions in the context of copulation remain to be explored. We tested the hypothesis that some central mechanisms could simultaneously recruit both pathways to the uterus. In this aim, we recorded intrauterine pressure changes in anesthetized female rats at the estrus stage after intracerebroventricular (ICV) administration of oxytocin (OT). Doses of 0.3-300 ng elicited increases of frequency and amplitude of uterine contractions. These effects were partly mimicked by the OT agonist [Thr(4),Gly(7)]OT but not by arginine vasopressin. They were blocked by the OT receptor antagonist atosiban delivered either ICV or intravenously. The latter suggests that ICV OT activated the systemic release of OT. The effects of OT were also blocked by hexamethonium, a ganglionic blocking agent, by atropine, a muscarinic receptor antagonist, and by N(omega)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis. The results reveal that ICV OT recruits autonomic efferent pathways to the uterus. These results support our hypothesis that the activation of central nuclei can promote uterine contractility, and that OT may be a central coordinator of autonomic and neuroendocrine pathways. The hypothalamus, the source of direct OT-ergic projections to the pituitary, the brain stem, and the spinal cord, may be a target of central OT.


Subject(s)
Central Nervous System/physiology , Oxytocin/pharmacology , Uterine Contraction/drug effects , Uterine Contraction/physiology , Animals , Atropine/pharmacology , Autonomic Nervous System/drug effects , Efferent Pathways/drug effects , Female , Ganglionic Blockers/pharmacology , Hexamethonium/pharmacology , Hormone Antagonists/pharmacology , Injections, Intraventricular , NG-Nitroarginine Methyl Ester/pharmacology , Oxytocin/administration & dosage , Oxytocin/agonists , Oxytocin/antagonists & inhibitors , Rats , Rats, Sprague-Dawley , Tocolytic Agents/pharmacology , Vasotocin/analogs & derivatives , Vasotocin/pharmacology
17.
Physiol Behav ; 83(2): 189-201, 2004 Nov 15.
Article in English | MEDLINE | ID: mdl-15488539

ABSTRACT

Penile erection is a vascular event controlled by the autonomic nervous system. The spinal cord contains the autonomic preganglionic neurons that innervate the penile erectile tissue and the pudendal motoneurons that innervate the perineal striated muscles. Sympathetic pathways are anti-erectile, sacral parasympathetic pathways are pro-erectile, and contraction of the perineal striated muscles upon activity of the pudendal nerves improves penile rigidity. Spinal neurons controlling erection are activated by information from peripheral and supraspinal origin. Both peripheral and supraspinal information is capable of either eliciting erection or modulating or inhibiting an erection already present. Sensory information from the genitals is a potent activator of pro-erectile spinal neurons and elicits reflexive erections. Some pre-motor neurons of the medulla, pons and diencephalon project directly onto spinal sympathetic, parasympathetic and pudendal motoneurons. They receive in turn sensory information from the genitals. These spinal projecting pathways release a variety of neurotransmitters, including biogenic amines (serotonin, dopamine, noradrenaline, and adrenaline) and peptides that, through interactions with many receptor subtypes, exert complex effects on the spinal network that controls penile erection. Some supraspinal structures (e.g. the paraventricular nucleus and the medial preoptic area of the hypothalamus, the medial amygdala), whose roles in erection have been demonstrated in animal models, may not project directly onto spinal pro-erectile neurons. They are nevertheless prone to regulate penile erection in more integrated and coordinated responses of the body, as those occurring during sexual behavior. The application of basic and clinical research data to treatment options for erectile dysfunction has recently proved successful. Pro-erectile effects of phosphodiesterase type 5 inhibitors, acting in the penis, and of melanocortin agonists, acting in the brain, illustrate these recent developments.


Subject(s)
Autonomic Nervous System/physiology , Neural Pathways/physiology , Penile Erection/physiology , Penis/innervation , Spinal Cord/physiology , Androgens/physiology , Animals , Autonomic Nervous System/cytology , Erectile Dysfunction/physiopathology , Humans , Male , Neural Pathways/cytology , Receptors, Neurotransmitter/physiology , Reflex/physiology , Sexual Behavior/physiology , Sexual Behavior, Animal/physiology , Spinal Cord/cytology
18.
Am J Physiol Regul Integr Comp Physiol ; 287(2): R446-53, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15044182

ABSTRACT

The rat uterus receives an innervation from the lumbosacral and thoracolumbar segments of the spinal cord. These segments receive descending oxytocinergic projections from the paraventricular nucleus of the hypothalamus. We tested the hypothesis that oxytocin regulates uterine motility through a spinal site of action. Oxytocin was administered in anesthetized female rats either intrathecally at the lumbosacral or thoracolumbar spinal cord levels or intravenously. Uterine activity was revealed by measuring changes of intrauterine pressure using an indwelling balloon placed in one caudal uterine horn. The uterus displayed a spontaneous activity characterized by intrauterine pressure rises, the frequency, amplitude, and duration of which were dependent on the stage of the estrous cycle. Oxytocin delivered at the lumbosacral level affected the frequency (during proestrus, estrus, and diestrus) and amplitude (during proestrus and estrus) of uterine activity. During estrus, oxytocin delivered at the thoracolumbar level affected the frequency, amplitude, and duration of the intrauterine pressure rises. Intravenous oxytocin not only affected intrauterine pressure rises (namely amplitude during proestrus and estrus and frequency and duration during estrus) but also increased the basal tone during estrus. The effects of lumbosacral oxytocin were partly mimicked by the oxytocin agonist [Thr(4),Gly(7)]-oxytocin blocked by the oxytocin receptor antagonist atosiban and by hexamethonium. Arginine vasopressin delivered at the lumbosacral level had no effect. These results support our hypothesis that oxytocin released by descending paraventriculo-spinal pathways and acting on spinal oxytocin receptors modulates the activity of the uterus. This regulation is cycle dependent.


Subject(s)
Oxytocin/analogs & derivatives , Oxytocin/pharmacology , Spinal Cord/physiology , Uterine Contraction/drug effects , Vasotocin/analogs & derivatives , Anesthesia , Animals , Diestrus , Estrus , Female , Ganglionic Blockers/pharmacology , Hexamethonium/pharmacology , Hormone Antagonists/pharmacology , Injections, Spinal , Lumbosacral Region , Metestrus , Pressure , Proestrus , Rats , Rats, Sprague-Dawley , Thoracic Vertebrae , Vasotocin/pharmacology
19.
Am J Physiol Regul Integr Comp Physiol ; 286(4): R710-8, 2004 Apr.
Article in English | MEDLINE | ID: mdl-14684562

ABSTRACT

The lumbosacral spinal network controlling penile erection is activated by information from peripheral and supraspinal origins. We tested the hypothesis that glutamate, released by sensory afferents from the genitals, activates this proerectile network. In anesthetized intact and T8 spinalized (i.e., freed from supraspinal inhibition) male rats, the parameters of electrical stimulation of the dorsal penile nerve (DPN) that elicited intracavernous pressure (ICP) rises were determined. In T8 spinalized rats, DPN stimulations were applied in the presence of d(-)-2-amino-5-phosphonopentanoic acid (d-AP5), a competitive NMDA receptor antagonist, or of 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulphonamide (NBQX), an AMPA-kainate receptor antagonist, injected intrathecally at the lumbosacral level. Both antagonists, alone or in combination, dose dependently decreased the ICP rise and increased its latency. In conscious rats, reflexive erections were depressed by d-AP5 and NBQX, as revealed by an increased latency of the first erection and by decreases of the number of rats displaying erections, of the number of erection clusters and of the number of erections per cluster. In anesthetized ats, the combined administration of the glutamatergic agonists NMDA and AMPA elicited ICP rises in the absence of DPN stimulation. In contrast, both agonists moderately decreased the ICP rise elicited by DPN stimulation but did not affect its latency. These results support our hypothesis that glutamate, released on stimulation of the genitals and acting at AMPA and NMDA receptors, is a potent reactivator of the spinal proerectile network.


Subject(s)
Glutamic Acid/physiology , Penile Erection/physiology , Spinal Cord/physiology , 2-Amino-5-phosphonovalerate/pharmacology , Anesthesia , Animals , Blood Pressure/drug effects , Catheterization , Dose-Response Relationship, Drug , Excitatory Amino Acid Agonists/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Male , Penile Erection/drug effects , Quinoxalines/pharmacology , Rats , Rats, Sprague-Dawley , Receptors, AMPA/agonists , Receptors, AMPA/antagonists & inhibitors , Receptors, AMPA/drug effects , Receptors, N-Methyl-D-Aspartate/agonists , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/drug effects , Spinal Cord/drug effects , Stimulation, Chemical
20.
J Soc Biol ; 198(3): 217-30, 2004.
Article in French | MEDLINE | ID: mdl-15662938

ABSTRACT

Activation of sacral parasympathetic pathways elicits penile erection through the release of vasorelaxant neurotransmitters that increase blood flow to the penis and relax the penile erectile tissue. Sympathetic pathways are antierectile. The pudendal pathway, responsible for the contraction of the perineal striated muscles, enhances an already present erection. All pathways originate in the spinal cord, but at various levels and areas. The convergence of information from peripheral and supra-spinal origins onto spinal neurones is very likely activating more specifically the spinal pro-erectile network. Peripheral information is the afferent limb of reflexive erections, impinges onto spinal interneurones and is able to activate or regulate the activity of sympathetic, parasympathetic and somatic nuclei. Supra-spinal information impinges onto either the same or a different spinal network. Premotor neurones located in supra-spinal structures, that project directly onto spinal sympathetic, parasympathetic or pudendal motoneurones, are present in the medulla, pons and diencephalon. Several of these premotor neurones may in turn be activated by sensory information from the genitals. Descending pathways release a variety of aminergic and peptidergic neurotransmitters in the vicinity of spinal neurones, thereby exerting complex effects on the spinal pro-erectile network. Brainstem and hypothalamic nuclei (among the latter, the paraventricular nucleus and the medial preoptic area) may not reach directly the spinal pro-erectile network. They are prone to regulate penile erection in more integrated and coordinated responses of the body, as those occurring during sexual behaviour. The pro-erectile central and spinal effects of neuropeptides such as oxytocin, melanocortins and endorphins have only recently been analyzed. Such compounds may represent therapeutic strategies to treat erectile dysfunction through a central site of action.


Subject(s)
Penile Erection/physiology , Penis/innervation , Androgens/physiology , Animals , Brain/physiology , Brain Diseases/complications , Brain Diseases/physiopathology , Erectile Dysfunction/etiology , Erectile Dysfunction/physiopathology , Erectile Dysfunction/therapy , Humans , Male , Models, Neurological , Motor Neurons/physiology , Neural Pathways/physiology , Neuropeptides/physiology , Orchiectomy , Parasympathetic Nervous System/physiology , Penile Erection/drug effects , Rats , Receptors, Neurotransmitter/drug effects , Receptors, Neurotransmitter/physiology , Spinal Cord/physiology , Spinal Cord Injuries/complications , Spinal Cord Injuries/physiopathology , Sympathetic Nervous System/physiology
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