Biomedical subjects

C Beyer

Publications and source records attributed to C Beyer.

At least 55 records · Page 3Linked to original sources

PubMed1998

Expression of aromatase in the embryonic and postnatal mouse striatum.

Estrogen influences striatal activity and the development of the nigrostriatal system. This study is concerned with the ontogenetic and postnatal expression of aromatase in the mouse striatum. Aromatase activity and mRNA expression were detectable in the embryonic striatum and increased postnatally with no differences between sexes. Aromatase-positive cells were uniformly distributed within the striatum. These data demonstrate that estrogen formation is an intrinsic property of striatal cells and suggest that estrogen may be important for striatal development and function.

Animals↗

PubMed1998

Administration of interleukin 13 to simian immunodeficiency virus-infected macaques: induction of intestinal epithelial atrophy.

Increase Th2 cytokine production may contribute to some clinical manifestations of HIV infection, and studies have suggested that IL-13 rather than IL-4 is involved in these conditions. We directly tested this hypothesis by administrating IL-13 to SIV-infected macaques. SIV-infected rhesus macaques received a daily subcutaneous injection for 21 days of either IL-13 (10 microg/kg/day) or a placebo. The four macaques treated with IL-13 experienced body weight loss (9.95 +/- 0.71%) related to intestinal tract damage: they all suffered from a complete atrophy of duodenal villi. This was presumably due to premature epithelial cell death: proliferating Ki67+ cells in glandular crypts were as numerous as in control animals, but many epithelial cells developed apoptosis. The duodenal mucosa was infiltrated with cells expressing CD56 and PEN5, two markers of NK cells, and there was a deregulation of local cytokine and chemokine production characterized by a decrease in IL-10 gene expression (25% of controls) and an increase in gene expression for IFN-gamma (4-fold control), MIP-1alpha (8-fold control), and MIP-1beta (13-fold control). Thus, IL-13 can induce digestive epithelial cell injury in vivo in primates infected with a retrovirus. Therefore, its role should be considered in digestive manifestations of HIV infection as well as in other disorders associated with intestinal epithelial atrophy.

Animals↗

PubMed1998

Differentiative effects of dopamine on striatal neurons involve stimulation of the cAMP/PKA pathway.

The neurotransmitter dopamine (DA) stimulates neurite outgrowth and growth cone formation in cultures of embryonic rat striatum through activation of D1 but not D2 receptors. We show here that neurite outgrowth could be stimulated to a similar extent by elevating cellular cAMP levels. Second, the neuritotrophic effect of DA was completely abolished by inhibiting adenylate cyclase or protein kinase A (PKA) but not protein kinase C (PKC). Third, double staining of cultures with antibodies against growth-associated protein-43 (GAP-43) and the phosphorylated form of the cAMP response element binding protein (pCREB) showed that pCREB was nearly exclusively associated with GAP-43-positive, i.e., actively growing, neurons. Again, this effect depended on D1 receptor and PKA activation. Although cross-talk with other signaling pathways needs to be studied further, we conclude that DA promotes the differentiation of striatal neurons via stimulation of D1 receptors and the cAMP/PKA signal transduction pathway.

Animals↗

PubMed1998

Ring A reductions of progestins are not essential for estrous behavior facilitation in estrogen-primed rats.

In Experiment 1 six dose levels (range 0.66-2000 microg) of progesterone (P) and two synthetic progestins with a double bond at C6: megestrol acetate (MA) and chlormadinone acetate (CA), which cannot be reduced at C5, were injected to estrogen-primed (2 microg estradiol benzoate 42 h earlier) ovariectomized (ovx) rats. The three progestins elicited significant lordosis and proceptive behaviors. Potency analysis showed that MA was the most potent progestin for stimulating estrous behavior, followed by P and CA. These results suggest that ring A reduction of progestins to 5alpha/5beta metabolites is not essential for the facilitation of estrous behavior in ovx estrogen-primed rats. Progestins with the 3-ketone group and a double bond at C4 can also be reduced at C3 to yield 3alpha-hydroxysteroid metabolites potentially capable of stimulating estrous behavior. In Experiment 2, the relevance of the formation of 3alpha-hydroxysteroid metabolites for estrous behavior facilitation was tested by concurrently injecting indomethacin (1.5 mg), a blocker of 3alpha-hydroxysteroid oxidoreductase, with 400 microg of P, MA, or CA to ovx estrogen-primed rats. Indomethacin failed to block the stimulatory effect of these progestins on estrous behavior. These results suggest that 3-ketosteroid reduction is also not essential for estrous behavior facilitation by progestins.

3-Hydroxysteroid Dehydrogenases↗

PubMed1998

Analgesic synergism between AP5 (an NMDA receptor antagonist) and vaginocervical stimulation in the rat.

Vaginocervical stimulation (VS) releases multiple neurotransmitters into superfusates of the spinal cord; these can stimulate both nociceptive (e.g., glutamate, and glycine acting at the NMDA site), and antinociceptive (e.g., GABA, norepinephrine, 5-HT, and glycine acting at the strychnine-sensitive receptor) systems. Although the balance between these two opposing systems can determine the nature, magnitude, and duration of the response to VS, the characteristic prevailing response to VS is analgesia. We hypothesized that by counteracting the nociceptive component of this system, the magnitude and duration of the response to VS would be augmented. In the present study, the NMDA receptor antagonist AP5 [10 microg injected intrathecally (i.t.)] significantly increased the magnitude and duration of the analgesia (measured as tail flick latency to radiant heat) produced by VS (200 g force). At several time points the analgesic effect of AP5 combined with VS was greater than the sum of the effects of AP5 and VS separately, suggesting that they act synergistically. We propose that AP5 potentiates the analgesic effect of VS by two mechanisms: (a) antagonizing the putative pain-producing action of glutamate and glycine acting jointly at the NMDA receptor, and consequently, (b) permitting the unimpeded expression of the analgesic action of inhibitory neurotransmitters released by VS (e.g., glycine at the strychnine-sensitive receptor, and GABA).

2-Amino-5-phosphonovalerate↗

PubMed1998

Developmental expression and regulation of aromatase- and 5alpha-reductase type I mRNA in the male and female mouse hypothalamus.

Androgen metabolites synthesized by neural aromatase and 5alpha-reductase are implicated in many aspects of mammalian brain development and, in particular, in the masculinization of distinct central nervous system structures and brain functions. The present study was designed to determine (1) the developmental profile of aromatase- and 5alpha-reductase type I mRNA expression in the mouse hypothalamus and (2) to relate ontogenetic sex differences in aromatase activity which have been described in the past to sex-specific aromatase gene expression. In addition, we analysed the effect of androgens on the perinatal regulation of hypothalamic aromatase and 5alpha-reductase type I mRNA expression. By applying semiquantitative reverse transcription-polymerase chain reaction analysis, we found hypothalamic aromatase mRNA expression to be developmentally regulated and to display sex differences at birth and on postnatal day 15 with higher mRNA levels in males. Newborn males and females, which were treated in utero with the androgen receptor antagonist cyproterone actetate, exhibited significantly reduced aromatase mRNA levels compared with untreated controls. In contrast to aromatase, expression levels of hypothalamic 5alpha-reductase mRNA did not reveal a clear-cut developmental profile or sex differences, and no regulatory role for androgens in controlling 5alpha-reductase mRNA expression was found. In conclusion, these results demonstrate perinatal sex differences in hypothalamic aromatase- but not 5alpha-reductase gene expression and suggest that sex differences in perinatal aromatase activity are reflected by corresponding differences in mRNA levels. Androgens are found to control brain estrogen formation pretranslationally at the level of aromatase gene expression. Our findings imply that sex differences in androgen availability and responsiveness are important regulatory factors for aromatase expression in the developing male hypothalamus.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1998

Nongenomic effects of oestrogen: embryonic mouse midbrain neurones respond with a rapid release of calcium from intracellular stores.

Evidence is emerging that oestrogen, besides acting via classical nuclear receptors, can rapidly influence the physiology of nerve cells through other mechanisms. Oestrogens have been shown to modulate the differentiation and function of embryonic midbrain dopaminergic neurones by stimulating neurite outgrowth, expression of tyrosine hydroxylase mRNA, dopamine uptake and release in spite of the fact that dopaminergic cells in the prenatal midbrain do not express the classical oestrogen receptor. This study therefore intended to unravel possible signal transduction pathways activated by oestrogen which might be associated with the above oestrogen effects. As a physiological second-messenger mechanism, we studied the influence of oestrogen on fluctuations of intracellular Ca2+ levels [Ca2+]i by microspectrofluorimetry of the Ca2+-sensitive indicator Fura-2, in primary cultures from embryonic mouse midbrains. 17Beta-estradiol (10 nM-1 pM) but not 17alpha-estradiol increased [Ca2+]i within 1-3 s in a dose-dependent way. Removal of extracellular Ca2+ abrogated K+-stimulated Ca2+ rise but did not affect 17beta-estradiol stimulation. Pretreatment of cells with thapsigargin (1 microM, 10 min), an inhibitor of Ca2+-pumping ATPases in the endoplasmic reticulum, abolished the 17beta-estradiol effect but not the K+-stimulated [Ca2+]i rise. Oestrogen effects on [Ca2+]i were completely mimicked by using a membrane-impermeant oestrogen-BSA construct. In order to identify oestrogen-sensitive cells, some cultures were subsequently immunostained for microtubule-associated protein II, tyrosine hydroxylase, or GABA. All oestrogen-sensitive cells were immunocytochemically characterized as neurones, and about half of these responsive neurones was found to be dopaminergic or GABAergic. These results demonstrate that 17beta-estradiol is capable of rapidly modulating physiological parameters of developing midbrain neurones by directly interacting with specific membrane binding sites coupled to a signal transduction mechanism that causes a calcium release from intracellular Ca2+ stores. It is suggested that oestrogen effects on differentiation and function of midbrain dopaminergic neurones are mediated by intracellular Ca2+ signalling.

Animals↗

PubMed1998

Developmental sex differences in estrogen receptor-beta mRNA expression in the mouse hypothalamus/preoptic region.

Estrogens play a significant role during mammalian brain development and are required for the masculinization of neuronal circuits involved in sex-specific behaviors and neuroendocrine functions. Cellular estrogen signalling is transmitted through nuclear estrogen receptors (ER) which are divided into two subforms: the ER-alpha as well as the recently cloned ER-beta have been demonstrated in the hypothalamus. In the present study, we have analyzed the sex-specific expression of ER-beta mRNA in the pre- and postnatal mouse hypothalamus/preoptic region (Hyp/POA) by semiquantitative RT-PCR. The ER-beta mRNA was detectable as early as embryonic day (E) 15 in the diencephalon of both sexes. In males, levels of mRNA expression in the Hyp/POA increased until birth and remained high throughout postnatal (P) development, whereas in females, such an increase was not observed. Significantly higher mRNA levels were detected in the male Hyp/POA from E17 until P15. Perinatal sex differences in ER-beta mRNA expression coincide with higher estrogen-forming rates in the male Hyp/POA. At present, no direct evidence is available which demonstrates that estrogen signalling through ER-beta is involved in brain development. However, data from our and other studies suggest a potential role for this signal transduction pathway for brain differentiation.

Animals↗

PubMed1998

Importance of mother/young contact at parturition and across lactation for the expression of maternal behavior in rabbits.

We prevented mother/pup contact at parturition or across early or midlactation to investigate the importance of such interaction for maintaining material behavior in rabbits. When pup contact was prevented across lactation Days 1-7 or 11-17 (by anesthetizing multiparous mothers during the oxytocin-induced milk letdown; Experiment 1), nursing incidence was reduced to 40% and 83%, respectively, on the day following anesthesia withdrawal. Both groups also showed a decreased milk output, long latencies to initiate nursing, and several entrances into the nest box not associated with nursing. In Experiment 2 we prevented mother/litter contact at parturition to determine the specific role of pup contact at this time. We found a reduction in the incidence of nursing on postpartum Day 1 from 80% (in control primiparous mothers) to 33%. By contrast, 100% of both deprived and control multiparous mothers displayed nursing on Day 1. These mothers also showed the unusual behaviors found in Experiment 1 and an extemporaneous nest-building. We conclude that: (a) mother/young contact at parturition is crucial for establishing maternal responsiveness in primiparous does, (b) the experience acquired by raising a previous litter allows the retention of maternal responsiveness despite a lack of pup contact at parturition, (c) maternal responsiveness is maintained across early lactation by daily interaction with pups, and (d) interaction with pups across midlactation allows the finely tuned display of maternal behavior.

Animals↗

PubMed1997

Protection of SIVmac-infected macaque monkeys against superinfection by a simian immunodeficiency virus expressing envelope glycoproteins of HIV type 1.

The infection of macaque monkeys by attenuated simian immunodeficiency virus can vaccinate against pathogenic molecular clones and isolates of the same virus. The correlates of this potent protective immunity are not fully understood but may be the key to an effective AIDS vaccine for humans. Aiming to determine whether host immune responses to envelope glycoprotein are an essential component of the immunity to primate lentiviruses, we have tried to superinfect SIVmac-infected macaque monkeys with SHIVsbg, a chimeric primate lentivirus constructed from the SIVmac239 genome with the env, rev, tat, and vpu genes from HIV-1 Lai. After inoculation of a large dose of SHIVsbg, the chimeric virus was isolated by coculture of mononuclear blood cells from four of five SIV-infected monkeys, but three animals were protected from extracellular SHIV viremia and did not seroconvert to HIV-1 glycoproteins. In the two SIV-infected monkeys that did develop SHIV viremia, cell-associated viral load was reduced at least 100-fold. These data indicate that an antiviral response capable of effectively controlling primate lentivirus replication might not necessarily involve the envelope glycoprotein.

AIDS Vaccines↗

PubMed1997

Androgens stimulate the morphological maturation of embryonic hypothalamic aromatase-immunoreactive neurons in the mouse.

Gonadal steroids play an important role as developmental factors for the rodent brain and are implicated in the sexual differentiation of neural structures. Estrogens have been linked to survival and plasticity of central neurons, thereby regulating the development of hypothalamic and limbic structures associated with reproductive functions. Besides estrogens, androgens also contribute actively to CNS maturation. We have shown recently that androgens stimulate the receptor-mediated functional differentiation of cultured hypothalamic aromatase-immunoreactive (Arom-IR) neurons by stimulating the expression of Arom, the key enzyme in estrogen formation. In the present study, we investigated whether androgens are capable of influencing morphological differentiation of hypothalamic Arom-IR neurons. Androgen treatment, unlike estrogen, stimulated the morphological differentiation of cultured embryonic hypothalamic Arom-IR cells by increasing neurite outgrowth and branching, soma size, and the number of stem processes. This effect was brain region- and transmitter phenotype-specific; neither cortical Arom-IR neurons nor hypothalamic GABAergic neurons responded to androgens. Moreover, morphogenetic effects depended on androgen receptor (AR) activation, since morphological changes were completely inhibited by flutamide. Double-labeling of hypothalamic Arom-IR neurons revealed a considerable number of cells coexpressing AR, whereas cortical Arom-IR cells did not label for AR. Our data demonstrate that androgens function as morphogenetic signals for developing hypothalamic Arom-IR cells, thus being potentially effective in influencing plasticity and synaptic connectivity of hypothalamic Arom-systems.

Androgens↗

PubMed1997

Sex differences in the regulation of embryonic brain aromatase.

Oestrogen formed from androgen by aromatization plays a critical role in the sexual differentiation of the male brain and behaviour. A question which has still to be answered is what regulates the gender-specific changes in aromatase activity forming oestrogen during sensitive periods of brain growth. Using a primary cell culture technique and sexed embryos, we have shown that in the fetal mouse brain, oestrogen formation in the male is neuronal rather than glial and aromatase activity is regionally localized, being higher in the hypothalamus than in the cortex. The aromatase activity measured from cells in culture has the same enzyme binding affinity (apparent Km approximately 40 nM) as intact brain samples. Neurones developing in the embryonic male brain (embryonic day (ED) 15) contain higher aromatase activity (Vmax, 895 fmol/h/mg protein) than the female (Vmax, 604). Although a sex difference exists at early stages of embryonic development (ED 13), the embryonic aromatase system is regulated by steroids later in fetal development. The developing aromatase-containing neuroblasts probably form processes which connect to other aromatase neurones. Immunoreactive staining with an aromatase polyclonal antibody identifies an increase in numbers of aromatase-immunoreactive hypothalamic neuronal cell bodies following testosterone treatment. Testosterone treatment also causes both stimulation of neurite growth and branching as well as functional maturation of aromatase neurones. In particular, there is an increase in aromatase activity per neurone as well as a dramatic increase in the number of neurones expressing the enzyme. Both the functional and morphological changes depend on androgen receptor stimulation for several days in vitro. This conclusion is supported by colocalization studies which reveal a high number of fetal hypothalamic aromatase neurones co-expressing androgen receptor. We conclude that testosterone influences the growth of male hypothalamic neurones containing aromatase at a sensitive period of brain development. Endogenous steroid inhibitors of aromatase, probably formed within the neuroglia, also play a role in the control of oestrogen production. An endogenous 5alpha-reduced metabolite of testosterone, 5alpha-androstanedione, is almost as potent in inhibiting neuronal hypothalamic aromatase activity (Ki = 23 nM) as the synthetic non-steroidal inhibitors such as the imidazole, fadrozole, and the triazoles, arimidex and letrozole. It is clear that the oestrogen-forming capacity of the male hypothalamus has the special characteristics and plasticity of regulation which could affect brain differentiation at specific steroid-sensitive stages in ontogeny.

Animals↗

PubMed1997

Progesterone receptor participates in the stimulatory effect of LHRH, prostaglandin E2, and cyclic AMP on lordosis and proceptive behaviours in rats.

We explored the effect of the antiprogestin RU486 on the estrous behaviour (lordosis and proceptivity) induced in sexually experienced ovariectomized oestrogen primed rats by: 5 microg luteinizing hormone-releasing hormone (LHRH), 100 microg prostaglandin E2 (PGE2), or 2 mg dibutyryl cyclic AMP (db cAMP). Pretreatment with 5 mg RU 486 (but not with vehicle) 60 min before the injection of the above-mentioned agents significantly decreased both lordosis and proceptive behaviours normally induced by such agents. Results suggest that the estrus-inducing action of LHRH, PGE2 and db cAMP occurs through the activation of the progesterone receptor.

Animals↗

PubMed1996

High viral load and CD4 lymphopenia in rhesus and cynomolgus macaques infected by a chimeric primate lentivirus constructed using the env, rev, tat, and vpu genes from HIV-1 Lai.

Chimeric primate lentiviruses composed of SIV and HIV genes may allow the analysis of the role of these discrete HIV genes in viral pathogenesis in macaque monkeys. We have constructed a chimeric virus in which the env, rev, tat, and vpu genes of HIV-1 Lai replace the env, rev, and tat genes of the SIVmac239 genome. This virus, SHIVsbg, replicates efficiently in rhesus (Indian and Chinese subspecies) and cynomolgus monkeys with viral loads in PBMC and lymph nodes of up to one infected cell per 30 cells during the acute phase of the infection. Sera from all monkeys recognize specific HIV-1 glycoproteins. The onset of lymphadenopathy in all animals was concurrent with a depletion of CD4 lymphocytes in peripheral blood. The virulence of this SHIV for rhesus and cynomolgus monkeys therefore closely parallels that of HIV-1 for human in the acute phase of the infection. Changes in the env and vpu genes of a molecular clone of HIV-1 can now be analyzed after passage in nonhuman primate species as the SHIVsbg replicates efficiently. The SHIVsbg-macaque model is an important step in the development of a readily available animal model for HIV-1 vaccine studies.

Animals↗

PubMed1996

Genotype-dependent sex differentiation of dopaminergic neurons in primary cultures of embryonic mouse brain.

In order to investigate genetic factors that interfere with hormone-mediated sex differentiation of dopaminergic neurons, we raised sex-specific primary cultures from embryonic day 13 diencephalon (D) or mesencephalon (M) of three different strains of mice, NMRI, CBA/J, and BALBc/J. Part of the cultures were maintained for 6 or 13 days in vitro (DIV) in medium containing 17 beta-estradiol or testosterone. The cultures were analyzed for sex differences in numbers of tyrosine hydroxylase-immunoreactive neurons, endogenous dopamine (DA) levels, and specific uptake of [3H]DA. Previous results obtained with cultures of embryonic Sprague-Dawley rats had shown that these parameters develop sex-specific characteristics in the absence of sex differences in hormone environment. Similar steroid-independent sex differences as they occur in the rat were found in M cultures of NMRI but not in CBA and BALBc mice. Long-term sex steroid treatment did not affect any of the above parameters in any strain. It is concluded that cell-autonomous realization of the genetic sex of dopaminergic neurons depends on the genetic background.

Analysis of Variance↗

PubMed1996

Oxytocin and vasopressin immunoreactivity in rabbit hypothalamus during estrus, late pregnancy, and postpartum.

Mother rabbits construct an elaborate maternal nest before parturition and display a single, brief, daily nursing bout throughout lactation. These features present a unique model for investigating the relevance of changes in neuroendocrine secretion associated with pregnancy and parturition for the regulation of maternal behavior. In the present study we analyzed changes in the location, somal size, and number of oxytocin (OT)- and arginine vasopressin (AVP)-immunoreactive (IR) neurons in the hypothalamus of rabbits in estrus, late pregnancy (day 29), and postpartum day 1. From estrus to late pregnancy, the number of OT-IR neurons increased in the scattered cell groups located in the lateral hypothalamic area (LHA), but not in the magnocellular nuclei, i.e., paraventricular nucleus (PVN) and supraoptic nucleus (SON). On postpartum day 1 the increase in the number of OT-IR neurons was sustained in the LHA and became apparent also in the main body of the PVN, in which the number of OT-IR neurons doubled. Increases in the somal size of OT-IR cells were seen in all three nuclei only on postpartum day 1. No OT-IR cells were found in the suprachiasmatic nucleus (SCN). From late pregnancy and into postpartum day 1 increases in the somal size of AVP-IR neurons were detected in the PVN, SON, and LHA but not in the SCN. The number of AVP-IR neurons increased between late pregnancy and postpartum day 1 in the SON only. The changes observed in OT and AVP expression in specific hypothalamic nuclei may be related to specific somatic and behavioral events occurring around the time of parturition, e.g., nest-building, maintenance of homeothermy, elevation of blood volume, and nursing in mother rabbits.

Animals↗

PubMed1996

Brain-mediated responses to vaginocervical stimulation in spinal cord-transected rats: role of the vagus nerves.

The present study was designed to ascertain whether the vagus nerves convey functional sensory activity from the reproductive tract in rats. Previously, vaginocervical mechanostimulation (VS) was shown to increase pupil diameter (PD) and the threshold of vocalization to tail shock (Voc-T). These responses were attenuated but not abolished by combined bilateral transection of the 'genito-spinal' nerves (i.e. pelvic, hypogastric and pudendal). Subsequent bilateral vagotomy further reduced or abolished the residual responses. In the present study, spinal cord transection above the known level of entry of the genito-spinal nerves was combined with bilateral vagotomy. In ovariectomized rats, after spinal cord transection at thoracic 7 (T7X), lumbar 5 (L5X) levels, or sham surgery (Sh), responses to VS were measured, the vagus nerves were then transected bilaterally, and responses to VS were again measured. VS significantly increased Voc-T and PD after sham procedure or spinal cord transection at either level. Subsequent bilateral vagotomy abolished the VS-induced increase in PD in the T7X group. Due to low survival rate, the effect of vagotomy on Voc-T could not be determined. Consequently, we performed a second experiment. In non-ovariectomized rats, VS significantly increased PD but reduced Voc-T in the T7X group compared to the Sh group, and subsequent bilateral vagotomy abolished both responses. These findings provide evidence that, in the rat, the vagus nerves provide a functional sensory pathway from the reproductive tract directly to the medulla oblongata of the brain, bypassing the spinal cord.

Analysis of Variance↗

PubMed1996

Vagotomy blocks responses to vaginocervical stimulation after genitospinal neurectomy in rats.

To ascertain whether any effects of vaginocervical stimulation (VS) are mediated by the vagus nerve, all known afferent nerves from the reproductive tract to the spinal cord were transected and the rats were tested for residual responses to VS. After combined bilateral transection of the pelvic, hypogastric, and pudendal nerves (NX), the following responses to VS were greatly reduced or abolished: lordosis to flank-perineum palpation, leg extension, immobilization, and blockage of both tail withdrawal to radiant heat and leg withdrawal to foot pinch. However, after these nerve cuts, the following persisted as significant residual responses to VS: 1) analgesia [measured as increase in vocalization threshold (VOCT) to tailshock], 2) pupil dilatation (PD), and 3) increase in heart rate (HR). Subsequent bilateral subdiaphragmatic vagotomy (VX) significantly reduced the magnitude of PD and abolished the analgesia. By contrast, VX produced no significant effect on the HR increase to VS. The above findings provide evidence that brain-mediated responses to vaginocervical stimulation can be elicited via the vagus nerves.

Afferent Pathways↗