Showing papers on "Area postrema published in 2017"

The circumventricular organs.

Abstract: The circumventricular organs (CVOs) are midline structures located around the third and fourth ventricles that are characterized by a lack of blood-brain barrier. The pineal gland, median eminence, neurohypophysis and the subcommisural organ are classified as secretory, whereas the subfornical organ, area postrema and the organum vasculosum of the lamina terminalis as the sensory CVOs. Glial cells consisting of astrocytes and microglia/macrophages are present in all these organs. The pineal gland, neurohypophysis and the median eminence lack the presence of neurons that are present in the rest of the circumventricular organs. Most of the circumventricular organs are lined by ependymal cells except the pineal and the neurohypophysis. Modified ependymal cells known as tanycytes are present in the ependymal lining. These organs are important sites for communication with the cerebrospinal fluid as well as between the brain and peripheral organs via blood-borne products as they lack the blood brain barrier.

Nucleus of the solitary tract, medullary reflexes, and clinical implications

Abstract: The nucleus of the solitary tract (solitary nucleus, nucleus tractus solitarii [NTS]), located in the dorsomedial medulla, is the first relay station for general visceral and taste afferents carried by the cranial nerves and has a critical role in the initiation and integration of a wide variety of reflexes controlling cardiovascular function, respiration, and gastrointestinal motility. Though isolated bilateral involvement of the NTS in neurologic disorders is infrequent, its intimate anatomical relationship with the fourth ventricle and the area postrema may underlie its major role in clinical manifestations such as those described in this representative case.

Circulating Ghrelin Acts on GABA Neurons of the Area Postrema and Mediates Gastric Emptying in Male Mice

Abstract: Ghrelin is known to act on the area postrema (AP), a sensory circumventricular organ located in the medulla oblongata that regulates a variety of important physiological functions. However, the neuronal targets of ghrelin in the AP and their potential role are currently unknown. In this study, we used wild-type and genetically modified mice to gain insights into the neurons of the AP expressing the ghrelin receptor [growth hormone secretagogue receptor (GHSR)] and their role. We show that circulating ghrelin mainly accesses the AP but not to the adjacent nucleus of the solitary tract. Also, we show that both peripheral administration of ghrelin and fasting induce an increase of c-Fos, a marker of neuronal activation, in GHSR-expressing neurons of the AP, and that GHSR expression is necessary for the fasting-induced activation of AP neurons. Additionally, we show that ghrelin-sensitive neurons of the AP are mainly γ-aminobutyric acid (GABA)ergic, and that an intact AP is required for ghrelin-induced gastric emptying. Overall, we show that the capacity of circulating ghrelin to acutely induce gastric emptying in mice requires the integrity of the AP, which contains a population of GABA neurons that are a target of plasma ghrelin.

Anorexia-cachexia syndrome in hepatoma tumour-bearing rats requires the area postrema but not vagal afferents and is paralleled by increased MIC-1/GDF15

Abstract: BACKGROUND: The cancer-anorexia-cachexia syndrome (CACS) negatively affects survival and therapy success in cancer patients. Inflammatory mediators and tumour-derived factors are thought to play an important role in the aetiology of CACS. However, the central and peripheral mechanisms contributing to CACS are insufficiently understood. The area postrema (AP) and the nucleus tractus solitarii are two important brainstem centres for the control of eating during acute sickness conditions. Recently, the tumour-derived macrophage inhibitory cytokine-1 (MIC-1) emerged as a possible mediator of cancer anorexia because lesions of these brainstem areas attenuated the anorectic effect of exogenous MIC-1 in mice. METHODS: Using a rat hepatoma tumour model, we examined the roles of the AP and of vagal afferents in the mediation of CACS. Specifically, we investigated whether a lesion of the AP (APX) or subdiaphragmatic vagal deafferentation (SDA) attenuate anorexia, body weight, muscle, and fat loss. Moreover, we analysed MIC-1 levels in this tumour model and their correlation with tumour size and the severity of the anorectic response. RESULTS: In tumour-bearing sham-operated animals mean daily food intake significantly decreased. The anorectic response was paralleled by a significant loss of body weight and muscle mass. APX rats were protected against anorexia, body weight loss, and muscle atrophy after tumour induction. In contrast, subdiaphragmatic vagal deafferentation did not attenuate cancer-induced anorexia or body weight loss. Tumour-bearing rats had substantially increased MIC-1 levels, which positively correlated with tumour size and cancer progression and negatively correlated with food intake. CONCLUSIONS: These findings demonstrate the importance of the AP in the mediation of cancer-dependent anorexia and body weight loss and support a pathological role of MIC-1 as a tumour-derived factor mediating CACS, possibly via an AP-dependent action.

Glial Endozepines Inhibit Feeding-Related Autonomic Functions by Acting at the Brainstem Level.

Abstract: Endozepines are endogenous ligands for the benzodiazepine receptors and also target a still unidentified GPCR The endozepine octadecaneuropeptide (ODN), an endoproteolytic processing product of the diazepam-binding inhibitor (DBI) was recently shown to be involved in food intake control as an anorexigenic factor through ODN-GPCR signaling and mobilization of the melanocortinergic signaling pathway Within the hypothalamus, the DBI gene is mainly expressed by non-neuronal cells such as ependymocytes, tanycytes, and protoplasmic astrocytes, at levels depending on the nutritional status Administration of ODN C-terminal octapeptide (OP) in the arcuate nucleus strongly reduces food intake Up to now, the relevance of extrahypothalamic targets for endozepine signaling-mediated anorexia has been largely ignored We focused our study on the dorsal vagal complex located in the caudal brainstem This structure is strongly involved in the homeostatic control of food intake and comprises structural similarities with the hypothalamus In particular, a circumventricular organ, the area postrema (AP) and a tanycyte-like cells forming barrier between the AP and the adjacent nucleus tractus solitarius (NTS) are present We show here that DBI is highly expressed by ependymocytes lining the fourth ventricle, tanycytes-like cells, as well as by proteoplasmic astrocytes located in the vicinity of AP/NTS interface ODN staining observed at the electron microscopic level reveals that ODN-expressing tanycyte-like cells and protoplasmic astrocytes are sometimes found in close apposition to neuronal elements such as dendritic profiles or axon terminals Intracerebroventricular injection of ODN or OP in the fourth ventricle triggers c-Fos activation in the dorsal vagal complex and strongly reduces food intake We also show that, similarly to leptin, ODN inhibits the swallowing reflex when microinjected into the swallowing pattern generator located in the NTS In conclusion, we hypothesized that ODN expressing cells located at the AP/NTS interface could release ODN and modify excitability of NTS neurocircuitries involved in food intake control

Involvement of Amylin and Leptin in the Development of Projections from the Area Postrema to the Nucleus of the Solitary Tract.

Abstract: The area postrema (AP) and the nucleus of the solitary tract (NTS) are important hindbrain centers involved in the control of energy homeostasis. The AP mediates the anorectic action and the inhibitory effect on gastric emptying induced by the pancreatic hormone amylin. Amylin’s target cells in the AP project to the NTS, an integrative relay center for enteroceptive signals. Perinatal hormonal and metabolic factors influence brain development. A postnatal surge of the adipocyte-derived hormone leptin represents a developmental signal for the maturation of projections between hypothalamic nuclei controlling energy balance. Amylin appears to promote neurogenesis in the AP in adult rats. Here, we examined whether amylin and leptin are required for the development of projections from the AP to the NTS in postnatal and adult mice by conducting neuronal tracing studies with DiI in amylin- (IAPP−/−) and leptin-deficient (ob/ob) mice. Compared to wild-type littermates, postnatal (P10) and adult (P60) IAPP−/− mice showed a significantly reduced density of AP-NTS projections. While AP projections were also reduced in postnatal (P14) ob/ob mice, AP-NTS fiber density did not differ between adult ob/ob and wild-type animals. Our findings suggest a crucial function of amylin for the maturation of neuronal brainstem pathways controlling energy balance and gastrointestinal function. The impaired postnatal development of neuronal AP-NTS projections in ob/ob mice appears to be compensated in this experimental model during later brain maturation. It remains to be elucidated whether an amylin- and leptin-dependent modulation in neuronal development translates into altered AP/NTS-mediated functions.

Functional and neurochemical characterization of angiotensin type 1A receptor-expressing neurons in the nucleus of the solitary tract of the mouse

Abstract: Angiotensin II acts via two main receptors within the central nervous system, with the type 1A receptor (AT1AR) most widely expressed in adult neurons. Activation of the AT1R in the nucleus of the solitary tract (NTS), the principal nucleus receiving central synapses of viscerosensory afferents, modulates cardiovascular reflexes. Expression of the AT1R occurs in high density within the NTS of most mammals, including humans, but the fundamental electrophysiological and neurochemical characteristics of the AT1AR-expressing NTS neurons are not known. To address this, we have used a transgenic mouse, in which the AT1AR promoter drives expression of green fluorescent protein (GFP). Approximately one-third of AT1AR-expressing neurons express the catecholamine-synthetic enzyme tyrosine hydroxylase (TH), and a subpopulation of these stained for the transcription factor paired-like homeobox 2b (Phox2b). A third group, comprising approximately two-thirds of the AT1AR-expressing NTS neurons, showed Phox2b immunoreactivity alone. A fourth group in the ventral subnucleus expressed neither TH nor Phox2b. In whole cell recordings from slices in vitro, AT1AR-GFP neurons exhibited voltage-activated potassium currents, including the transient outward current and the M-type potassium current. In two different mouse strains, both AT1AR-GFP neurons and TH-GFP neurons showed similar AT1AR-mediated depolarizing responses to superfusion with angiotensin II. These data provide a comprehensive description of AT1AR-expressing neurons in the NTS and increase our understanding of the complex actions of this neuropeptide in the modulation of viscerosensory processing.

Role of the abdominal vagus and hindbrain in inhalational anesthesia-induced vomiting

Abstract: The incidence of postoperative nausea and vomiting (PONV) can be as high as 80% in patients with risk factors (e.g., females, history of motion sickness). PONV delays postoperative recovery and costs several hundred million dollars annually. Cell-based assays show that halogenated ethers (e.g., isoflurane) activate 5-HT3 receptors, which are found on gastrointestinal vagal afferents and in the hindbrain - key pathways for producing nausea and vomiting. This project evaluated the role of the vagus and activation of the hindbrain in isoflurane-induced emesis in musk shrews, a small animal model with a vomiting reflex, which is lacking in rats and mice. Sham-operated and abdominal vagotomized shrews were exposed to 1 to 3% isoflurane to determine effects on emesis; vagotomy was confirmed by lack of vagal transport of the neuronal tracer Fluoro-Gold. In an additional study, shrews were exposed to isoflurane and hindbrain c-Fos was measured at 90min after exposure using immunohistochemistry. There were no statistically significant effects of vagotomy on isoflurane-induced emesis compared to sham-operated controls. Isoflurane exposure produced a significant increase in c-Fos-positive cells in the nucleus of the solitary tract and vestibular nuclei but not in the area postrema or dorsal motor nucleus. These results indicate that the abdominal vagus plays no role in isoflurane-induced emesis and suggest that isoflurane activates emesis by action on the hindbrain, as shown by c-Fos labeling. Ultimately, knowledge of the mechanisms of inhalational anesthesia-induced PONV could lead to more targeted therapies to control PONV.

Effects of intraperitoneally administered l-histidine on food intake, taste, and visceral sensation in rats

Abstract: To evaluate relative factors for anorectic effects of l-histidine, we performed behavioral experiments for measuring food and fluid intake, conditioned taste aversion (CTA), taste disturbance, and c-Fos immunoreactive (Fos-ir) cells before and after i.p. injection with l-histidine in rats. Animals were injected with saline (9 ml/kg, i.p.) for a control group, and saline (9 ml/kg, i.p.) containing l-histidine (0.75, 1.5, 2.0 g/kg) for a l-histidine group. Injection of l-histidine decreased the average value of food intake, and statistically significant anorectic effects were found in animals injected with 1.5 or 2.0 g/kg l-histidine but not with 0.75 g/kg l-histidine. Taste abnormalities were not detected in any of the groups. Animals injected with 2.0 g/kg l-histidine were revealed to present with nausea by the measurement of CTA. In this group, a significant increase in the number of Fos-ir cells was detected both in the area postrema and the nucleus tractus solitarius (NTS). In the 0.75 g/kg l-histidine group, a significant increase in the number of Fos-ir cells was detected only in the NTS. When the ventral gastric branch vagotomy was performed, recovery from anorexia became faster than the sham-operated group, however, vagotomized rats injected with 2.0 g/kg l-histidine still acquired CTA. These data indicate that acute anorectic effects induced by highly concentrated l-histidine are partly caused by induction of nausea and/or visceral discomfort accompanied by neuronal activities in the NTS and the area postrema. We suggest that acute and potent effects of l-histidine on food intake require substantial amount of l-histidine in the diet.

Suckling induced activation pattern in the brain of rat pups.

Abstract: Objectives: The aim of the study was to understand the effects of suckling on the brain of the pups by mapping their brain activation pattern in response to suckling.Methods: The c-fos method was applied to identify activated neurons. Fasted rat pups were returned to their mothers for suckling and sacrificed 2 hours later for Fos immunohistochemistry. Double labeling was also performed to characterize some of the activated neurons. For comparison, another group of fasted pups were given dry food before Fos mapping.Results: After suckling, we found an increase in the number of Fos-immunoreactive neurons in the insular and somatosensory cortices, central amygdaloid nucleus (CAm), paraventricular (PVN) and supraoptic hypothalamic nuclei, lateral parabrachial nucleus (LPB), nucleus of the solitary tract (NTS), and the area postrema. Double labeling experiments demonstrated the activation of calcitonin gene-related peptide-ir (CGRP-ir) neurons in the LPB, corticotropin-releasing hormone-ir (CRH-ir) but not oxy...

The use of siRNA as a pharmacological tool to assess a role for the transcription factor NF-IL6 in the brain under in vitro and in vivo conditions during LPS-induced inflammatory stimulation.

Abstract: Background Studies with NF-IL6-deficient mice indicate that this transcription factor plays a dual role during systemic inflammation with pro- and anti-inflammatory capacities. Here, we aimed to characterize the role of NF-IL6 specifically within the brain. Methods In this study, we tested the capacity of short interfering (si) RNA to silence the inflammatory transcription factor nuclear factor-interleukin 6 (NF-IL6) in brain cells under in vitro and in vivo conditions. Results In cells of a mixed neuronal and glial primary culture from the rat area postrema (AP), short interfering RNA (siRNA) directed against NF-IL6 strongly reduced basal and lipopolysaccharide (LPS)-induced nuclear immunoreactivity of this transcription factor, with the strongest effect on astrocytes. The siRNA did not exert inflammatory effects in the primary culture as confirmed by unaltered levels of IL-6 in supernatants. In vivo, intracerebroventricular (i.c.v.) injections of fluorochrome labelled siRNA caused its appearance in relevant brain structures for fever induction pathways such as the vascular organ of lamina terminalis, the subfornical organ, the median preoptic nucleus (MnPO) and the AP in several cell types, including microglial cells. However, i.c.v. injections of siRNA per se caused signs of fever, anorexia and reduced locomotor activity, i.e. sickness behavior. Conclusions This approach was, thus, not suitable to characterize the role NF-IL6 in the brain in vivo, namely during experimentally induced systemic inflammation.

Central Nervous System Control of Glucose Homeostasis

Abstract: Hypothalamus and brain stem play important roles in Glucose Homeostasis. There are two types of cells in the hypothalamus: Glucose excited (GE) and Glucose inhibited (GI). GE increases glucose concentration and GI decreases glucose concentration. They are located in ventromedial (VMH), arcuate, lateral, dorsomedial and paraventricular areas of hypothalamus. Nucleus of solitary tract, area postrema, dorsomedial nucleus of vagus and basolateral medulla are also related to glucose homeostasis. VMH contains sympathetic nucleus and upregulates plasma glucose and decreases hepatic glycogen, while lateral hypothalamus contains parasympathetic and down regulates plasma glucose. Through Glut-1, dependent transport glucose enters neurons and astrocytes. Glucose is metabolized and provides energy for GE and GI neurons. Their activity is guided by blood sugar level. Blood sugar level sends numerous signals through vagal pathway from periphery. Neuron astrocyte establishes via autonomic system connections with liver, pancreas, adrenal gland and maintains glucose homeostasis. Post prandial glucose levels are regulated by CNS.

Electrophysiological analysis of neurons in the area postrema

Abstract: This mini-review highlights electrophysiological studies of neurons in the area postrema, including studies using anesthetized animals, neurons in the brain slices, and cultured cells. Electrophysiological studies have demonstrated chemosensitivities, intrinsic membrane properties, synaptic responses and the receptive mechanism of several peptides. For seven decades, electrophysiological research has produced much of what we know about the behavior of postrema neurons. This and other issues are presented and discussed in this paper.

Overview of the neurokinin-1 receptor antagonists

Abstract: Neurokinin-1 (NK-1) receptor antagonists block substance P-mediated NK-1 receptors which are present in the abdominal vagus, the brainstem, and the area postrema in the brainstem. Substance P is a mammalian tachykinin that is found in vagal afferent neurons innervating the brainstem and sends impulses to the vomiting center (1). Compounds that block NK-1 receptors lessen emesis after cisplatin, ipecac, apomorphine, and radiation therapy (1).

Burning Redoxstats in the Brainstem: Lack of Nrf2 and the Rise of Hypertension.

Abstract: See related article, pp 1198–1206 > The most altruistic and sustainable philosophies fail > > before the brute brain stem imperative of self-interest > > —Peter Watts, Blindsight Hypertension is a serial killer, and for most, a silent and slow one. Abnormalities in the autonomic control of cardiovascular functions are central factors in hypertension pathogenesis. Blood-borne signals originating from baroreceptors and chemoreceptors can additionally feedback to the central nervous system, regulating autonomic output, via structures that lack a normal blood–brain barrier—such as the subfornical organ, organum vasculosum of the lamina terminalis, and area postrema. These critical, central controllers of autonomic function then communicate with other regions of the central nervous system, such as the hypothalamic and medullary autonomic centers, via efferent neural projections. Most of these autonomic alterations originate from the ventrolateral medulla oblongata, namely within the pressor region of the rostral ventrolateral medulla (RVLM). This longitudinal nucleus contains subsets of sympathetic premotor neurons that preferentially, or even exclusively, regulate sympathetic outflow directed to the heart or blood vessels. On stimulation, these neuronal units increase arterial pressure and heart rate (HR) and are readily silenced when blood pressure raises, coinciding with the abolition of sympathetic nerve activity. Although this region of the brain stem senses pressor signals from the periphery or central regions, such as the hypothalamus or amygdala, RVLM neurons can in fact receive autocrine, paracrine, and endocrine influences. These chemosensory signals are key in the regulation of arterial pressure, myocardial function, and salt and water balance and, thus, contributing to overall cardiovascular homeostasis. RVLM neurons, along with the paraventricular nucleus of the hypothalamus, can be targeted by acute excitatory influences, such as tumor necrosis factor-α infusion, thereby increasing arterial blood pressure, HR, and renal sympathetic nerve activity (RSNA).1 Importantly, in response to tumor necrosis factor-α or other chemosensory stimuli, RVLM neurons can …

Concurrent Dawson's Fingers and Area Postrema Lesion in a Mixed Neuroimmune Disorder.

Abstract: We report an example of imaging features of neuromyelitis optica spectrum disorder (NMOSD) that overlapped those of multiple sclerosis (MS), a coexistence that raises questions about how disease-specific these features may actually be and implications for treatment. Although distinctive imaging findings can often help to differentiate NMOSD from MS, the overlap between both disorders remains an open area of study. Furthermore, when the diagnostic criteria for NMOSD were revised in 2015, the International Panel for NMO Diagnosis agreed that non–organ-specific systemic autoimmunity may not only coexist with NMO but support its diagnosis. Our case also highlights this concept because our patient demonstrated several laboratory features of autoimmunity. A 57-year-old, right-handed, African-American woman with history of hypertension and recently diagnosed nondiabetic gastroparesis (8% emptying over 90 minutes) was admitted to our hospital with acute left-sided weakness and tingling. Additional history included intractable nausea, vomiting, and 60-lb weight loss over a 3-month period. She also described far-gaze binocular diplopia, bilateral lower extremity pain, and tingling sensation in extremities with neckmovement. Family history was significant for breast and lung cancer in several firstand second-degree relatives. Examination revealed left lateral gaze palsy, horizontal nystagmus, left-sided hyperalgesia within the trigeminal distribution of V1-V3, left-sidedweakness that wasmost prominent in hip flexors, diffuse hyperreflexia, ankle clonus, and left-sided Hoffman’s but otherwise absent Babinski signs. Sensory examination showed marked loss of vibration in distal joints of all extremities, loss of proprioception in bilateral toes, and patchy (nonlocalizing) areas of either decreased or increased perception for light touch and pinprick. She required bilateral assistance to stand up from sitting and walk. Diagnostic workup of serum and cerebrospinal fluid revealed additional abnormalities in immunological tests. Findings included positive antinuclear antibody screen with speckled pattern (titer 1:80), elevated sedimentation rate (71mm/hour), and elevated C-reactive protein (36.4mg/l). Specific serum antibodies were elevated: neuronal voltage-gated potassium channel antibodies, 0.41 (0.0-0.02); Anti-Sjögren’s-syndrome-related antigen A (SSA), 2.27 (0.0-0.9); Anti-Sjögren’s-syndrome-related antigen B (SSB), 1.61 (0.0-0.9); anti Jo-1, 1.36 (0.0-0.9); and positive anti-aquaporin 4 antibodies (AQP-4). Tests for anti-neutrophil cytoplasmic antibodies, double-stranded DNA, scleroderma 70kD, anti-smith antibodies, antimyeloperoxidase antibodies, beta-2 glycoprotein, and cryoglobulin were negative. Cerebrospinal fluids showed a predominantly lymphocytic pleocytosis (89 cells/mm); protein, 28mg/dl; glucose, 61 mg/dl (serum, 98 mg/dl); negative gram stain and culture; immunoglobulin G index elevated to 1.1; and two matched oligoclonal bands were identified. Cytology and other viral studies were negative. Brain magnetic resonance imaging (MRI) showed areas of increased signal intensity perpendicular to the lateral ventricles (Dawson’s fingers) and within the area postrema (Figure 1). No abnormal findings were seen on MRI of the thoracic spine or contrast-enhanced computed tomography scans of the chest, abdomen, and pelvis. Clinical rheumatological evaluation failed to confirm a clinical diagnosis of lupus or Sjögren’s syndrome. The patient remained stable and was scheduled to start rituximab infusions. In addition to the multiple lesions shown (Figure 1), other brain areas involved by the disease included parts of the left pons, right cerebellum, and left thalamus. The multifocal nature of the disease could potentially explain the wide range of clinical manifestations observed (e.g. cranial nerves palsies, motor and sensory disturbances). NMOSD was the most likely diagnosis given the specificity of anti AQP-4 antibodies and area postrema involvement. Despite extensive evaluation and close follow-up of our patient, no clinical evidence for rheumatological disease was found. Although the presence of concurrent autoimmunity in NMOSD has been previously described and occasionally thought to be part of a more generalized paraneoplastic process, the clinical significance of such serological findings is unclear. It remains an open question whether coexistent non–organ-specific autoimmunity in NMOSD is part of the syndrome or is a separate finding indicative of increased predisposition to autoimmune disorders or, alternatively, a false-positive laboratory finding. Contrasting with the classic NMO presentation of recurrent optic neuritis or longitudinal spinal cord lesion, our patient’s severe nausea and vomiting were most likely a manifestation of area postrema involvement, confirming earlier observations and the importance of considering NMOSD in cases of intractable vomiting. The presence of antibodies against voltage-gated potassium channels possibly hindered peristalsis and manifested as gastroparesis. Our case illustrates an example of classic imaging features of NMO overlapping those of MS. Area postrema hyperintensity on brain MRI, considered highly suggestive of NMOSD, is atypical in MS. In contrast, corpus callosal lesions perpendicular to the lateral ventricle (i.e. Dawson’s fingers) are highly suggestive radiographic findings of MS and maybe considered a red flag for diagnosis of NMOSD (except for longitudinal callosal lesions). The coexistence of these MRI signal characteristics is in line with earlier reports that such patterns may not be as diseasespecific as currently believed. In a study of Taiwanese patients with MS or NMOSD, imaging patterns considered to be specific failed to distinguish the two conditions: 11 (44%) of 25 NMOSD patients and 16 (55%) of 29 MS patients showed findings consistent with Dawson’s fingers. In striking contrast, Matthews et al reported Dawson’s fingers in none of the 26 patients with NMOSD versus 41 (82%) of 50 patients with MS. Such discrepancies in observations may suggest that these imaging patterns are indicative of ethnic variations or simply the diversity of idiosyncratic response patterns; however, we found no reports of unique imaging for MS or NMOSD in populations of African descent. Because of the involvement of area postrema