Role of the area postrema in three putative measures of motion sickness in the rat

Sutton, Richard L.; Fox, Robert; Daunton, Nancy G.

doi:10.1016/s0163-1047(88)90841-2

Cited by 24 publications

(10 citation statements)

References 40 publications

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“…Central GLP‐1R signalling has been implicated in mediating interoceptive stress, specifically in the CeA and NTS , and the AP, CVLM, PBNle and CeA are involved in viscerosensory processing and developing CFA . However, we did not detect any differences in the number of c‐Fos expressing cells in these brain areas between SDA and sham rats after Ex‐4 administration.…”

Section: Discussioncontrasting

confidence: 88%

Vagal Afferents Mediate Early Satiation and Prevent Flavour Avoidance Learning in Response to Intraperitoneally Infused Exendin‐4

Labouesse

Stadlbauer

Weber

et al. 2012

J Neuroendocrinology

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Glucagon-like peptide-1 receptor (GLP-1R) agonists such as exendin-4 (Ex-4) affect eating and metabolism and are potential candidates for treating obesity and type II diabetes. In the present study, we tested whether vagal afferents mediate the eating-inhibitory and avoidance-inducing effects of Ex-4. Subdiaphragmatic vagal deafferentation (SDA) blunted the short-term (< 1 h) but not long-term eating-inhibitory effect of i.p.-infused Ex-4 (0.1 μg/kg) in rats. A dose of 1 μg/kg Ex-4 reduced 0.5, 1, 2 and 4 h cumulative food intake in SDA and sham-operated rats to a similar extent. Paradoxically, SDA but not sham rats developed a conditioned flavour avoidance (CFA) after i.p. Ex-4 (0.1 μg/kg). SDA completely blunted the induction of c-Fos expression by Ex-4 in the hypothalamic paraventricular nucleus. Ex-4, however, increased the number of c-Fos expressing cells, independent of intact vagal afferents, in the nucleus accumbens and in the central nucleus of the amygdala, the lateral external parabrachial nucleus, the caudal ventrolateral medulla and the dorsal vagal complex. These data suggest that intact vagal afferents are only necessary for the full expression of the early satiating effect of Ex-4 but not for later eating-inhibitory actions, when circulating Ex-4 might reach the brain via the circulation. Our data also dissociate the satiating and avoidance-inducing effects of the low Ex-4 dose tested under our conditions and suggest that vagal afferent signalling may protect against the development of CFA. Taken together, these findings reveal a complex role of vagal afferents in mediating the effects of GLP-1R activation on ingestive behaviour.

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Section: Discussioncontrasting

confidence: 88%

Vagal Afferents Mediate Early Satiation and Prevent Flavour Avoidance Learning in Response to Intraperitoneally Infused Exendin‐4

Labouesse

Stadlbauer

Weber

et al. 2012

J Neuroendocrinology

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“…However, there are no known activators of HNMT at present; thus, we could not use HNMT activators to verify these results in reverse. Due to the lack of vomiting reflex, conditioned taste aversion was used as the index of motion sickness in the rats (Ossenkopp, 1983;Fox and McKenna, 1988;Sutton et al, 1988;Gallo et al, 1999;Li et al, 2005); thus, bias or mistake may be made when results obtained in the experiments using rats are used to explain a phenomenon developed in the humans. Therefore, dogs were used in the experiments of the present study to verify the results from rat experiments.…”

Section: Discussionmentioning

confidence: 99%

“…Conditioned taste aversion, as suggested by the literature (Ossenkopp, 1983;Fox and McKenna, 1988;Sutton et al, 1988;Gallo et al, 1999;Li et al, 2005), was used as the index of rat motion sickness. Before the rotatory stimulus, saccharin sodium solution (SSS; 0.15%) was provided for the rats to drink for 45 minutes when they had been deprived of water for a 24-hour period and had become familiar with this novel fluid 1 day before water deprivation through free access to 0.15% SSS in addition to tap water for another 24 hours.…”

Section: Methodsmentioning

confidence: 99%

Reduction of Motion Sickness Through Targeting Histamine N-Methyltransferase in the Dorsal Vagal Complex of the Brain

Chen

Chang

et al. 2018

J Pharmacol Exp Ther

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To investigate the role of histamine -methyltransferase (HNMT) activity in the development of motion sickness (MS) in the dorsal vagal complex (DVC) to inform the development of new drugs for MS, Beagle dogs and Sprague-Dawley rats were rotated to simulate MS. HNMT expression in the brain stem and DVC was measured. The effects of systemic application of tacrine, an HNMT inhibitor, on the development of MS were observed. Moreover, we microinjected a histamine receptor H1 inhibitor, promethazine, into the DVC to verify the involvement of histaminergic neurotransmission in MS. Finally, lentiviral vectors were microinjected into the DVC to determine the effects of altered HNMT expression on MS. We found the following: 1) HNMT expression in the medulla oblongata of dogs and rats insusceptible to MS was higher than in susceptible animals; 2) tacrine dose-dependently promoted MS in both animals and raised histamine level in rat medulla oblongata; 3) blocking histaminergic neurotransmission in the DVC with promethazine inhibited MS; 4) rotatory stimulus induced an elevation in HNMT expression, and vestibular training elevated the basal level of HNMT in the DVC during habituation to MS; 5) in vivo transfection of a lentiviral vector packaged with the HNMT gene increased HNMT expression in the DVC and reduced MS; and 6) microinjection of a lentiviral vector driving the interference of HNMT gene expression in vivo significantly inhibited HNMT expression in the DVC and exacerbated MS. In conclusion, HNMT expression in the brain stem is inversely correlated with MS development. Increasing HNMT expression or stimulating its activity in the DVC could inhibit MS.

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“…Area postrema has been implicated as a trigger zone for motion-induced emesis in the dog (Wang and Chinn, 1954) and monkey (Brizzee et al, 1980). However, more recent results are not as definite regarding its functional role (Borison and Borison, 1986;Wilpizeski et al, 1986;Sutton et al, 1988;Fox et al, 1990), and precisely how the area postrema affects vestibular reflex responses is still controversial (Jovanovic-Micic and Strbac, 1989;Gallo et al, 199 1). Interaction of the area postrema with other areas, for example, the solitary nucleus (Hay and Bishop,199 l), might be involved with homeostatic mechani ns controlling cardiovascular responses and electrolyte balance.…”

Section: Arsanilate Labyrinthectomymentioning

confidence: 99%

Fos-defined activity in rat brainstem following centripetal acceleration

1992

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To identify rat brainstem nuclei involved in the initial, shortterm response to a change in gravito-inertial force, adult Long-Evans rats were rotated in the horizontal plane for 90 min in complete darkness after they were eccentrically positioned off the axis of rotation (off-axis) causing a centripetal acceleration of 2 g. Neural activation was defined by the brainstem distribution of the c-fos primary response gene protein, Fos, using immunohistochemistry.The Fos labeling in off-axis animals was compared with that of control animals who were rotated on the axis of rotation (on-axis) with no centripetal acceleration, or who were restrained but not rotated. In the off-axis animals there was a significant labeling of neurons: in the inferior, medial, and y-group subnuclei of the vestibular complex; in subnuclei of the inferior olive, especially the dorsomedial cell column; in midbrain nuclei, including the interstitial nucleus of Cajal, nucleus of Darkschewitsch, Edinger-Westphal nucleus, and dorsolateral periaqueductal gray; in autonomic centers including the solitary nucleus, area postrema, and locus coeruleus; and in reticular nuclei including the lateral reticular nucleus and the lateral parabrachial nucleus. Also, there was greater Fos expression in the dorsomedial cell column, the principal inferior olive subnuclei, inferior vestibular nucleus, the dorsolateral central gray, and the locus coeruleus in animals who had their heads restrained compared to animals whose heads were not restrained. As one control, the vestibular neuroepithelium was destroyed by injecting sodium arsanilate into the middle ear, bilaterally. This resulted in a complete lack of Fos labeling in the vestibular nuclei and the inferior olive, and a significant reduction in labeling in other nuclei in the off-axis condition, indicating that these nuclei have a significant labyrinth-sensitive component to their Fos labeling. The data indicate that several novel brainstem regions, including the dorsomedial cell column of the inferior olive and the periaqueductal gray, as well as more traditional brainstem nuclei including vestibular and oculomotor related nuclei, respond to otolith activation during a sustained centripetal acceleration.Received Mar. 2, 1992; revised June 5, 1992; accepted June 12, 1992. We thank Jaw-Hem Lee and Huna Nauven for their sutmortine work in our labs. This work is made possible by a griduate student researchepprogram fellowship and NIH Grants DC01086, NS19208, DC001 10, DE06682, and DA06687.Correspondence should be addressed to Alvin J. Normal coordination of body movement and posture depends upon an accurate spatial reference. The otolith organs of the vestibular labyrinth are sensitive to the direction and magnitude of the earth's gravity and could provide a reference for integrating vestibular, visual, and somatosensory information to help control movement. When a sustained change in the gravitoinertial force occurs (e.g., from a novel linear motion, in a microgravity environment, or as a result of inner ear...

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Role of the area postrema in three putative measures of motion sickness in the rat

Cited by 24 publications

References 40 publications

Vagal Afferents Mediate Early Satiation and Prevent Flavour Avoidance Learning in Response to Intraperitoneally Infused Exendin‐4

Vagal Afferents Mediate Early Satiation and Prevent Flavour Avoidance Learning in Response to Intraperitoneally Infused Exendin‐4

Reduction of Motion Sickness Through Targeting Histamine N-Methyltransferase in the Dorsal Vagal Complex of the Brain

Fos-defined activity in rat brainstem following centripetal acceleration

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