Motoi Kobashi

Response of neurons in the solitary tract nucleus, area postrema and lateral parabrachial nucleus to gastric load of hypertonic saline

c-Fos was induced in the solitary tract nucleus (NTS), area postrema (AP) and lateral parabrachial nucleus (LPB) by the intragastric injection of hypertonic saline. The effect was bilateral and most dramatic in the NTS caudal to the facial nucleus and the AP, the areas receiving dense vagal afferent projection from the subdiaphragmatic structures. At least a part of these Fos-LI is considered to have been induced by the activation of the visceral osmoreceptors.

Involvement of specific orexigenic neuropeptides in sweetener-induced overconsumption in rats ☆

Palatability is one of the factors that regulates food and fluid intake and contributes to overconsumption in turn contributing to obesity. To elucidate the brain mechanisms of the palatability-induced ingestion, we explored the roles of six hypothalamic orexigenic neuropeptides, orexin, melanin-concentrating hormone (MCH), neuropeptide Y (NPY), agouti-related protein (AgRP), ghrelin and dynorphin, in the intake of a palatable solution, saccharin. Of the six peptides, intracerebroventricular (i.c.v.) administrations of orexin, MCH and NPY increased the intake of saccharin. Drinking of saccharin in turn elevated the mRNA levels of orexin and NPY, but not MCH. Pre-treatments of naloxone, an opioid antagonist, blocked the orexigenic effects of orexin and NPY. Specific gastric motor responses induced by central orexin-A and NPY are well known, however, MCH did not induce such responses. The i.c.v. administration of orexin-A facilitated gastric emptying. These results suggest that the overconsumption promoted by sweet and palatable tastes is attributed to the activation of orexigenic neuropeptides, such as orexin and NPY, and a downstream opioid system together with enhanced digestive functions.

Differences in autonomic responses between subjects with and without nausea while watching an irregularly oscillating video

Prodromal signs such as cardiac rhythm disturbance and changes in gastric motility are generally induced before and during nausea in humans. These autonomic reactions were compared in subjects who were or were not experiencing nausea. Nausea was induced by having the subjects view a movie of oscillating pictures. Seventeen healthy volunteers were asked to relax their muscles and watch the movie. Electrogastrogram (EGG), electrocardiogram (ECG), palmar and metopic perspiration, digital blood flow and thoracic movement related to respiration were simultaneously measured while the subjects viewed the movie. A total of 11 of 17 subjects complained of nausea after watching the movie. The characteristic changes in their autonomic responses during exposure to the movie were as follows. The power of the EGG, heart rate and metopic perspiration significantly increased compared to those before watching the movie. The respiratory cycle gradually increased during and even after watching the movie. In contrast, no significant changes in the power of the EGG, heart rate and metopic perspiration were observed in the remaining six subjects who did not experience nausea. The role of the autonomic nervous system in nausea is discussed. These results suggest that these symptoms regarding the sympathetic nervous system could actually be defensive reactions against the sensation of nausea.

Chemosensitive neurons in the area postrema of the rat and their possible functions

Abstract The present study is an attempt to demonstrate Chemosensitive neurons within the area postrema (AP) electrophysiologically. Three types of Chemosensitive neurons were identified: 1. 1) glucose-responsive neurons that may participate in control of blood glucose and satiation, 2. 2) sodium (osmotic pressure)-responsive neurons that may contribute to control of sodium and water balance of the body fluid and may be involved in salt appetite, 3. 3) nausea-related neurons which respond to excess distension of stomach and LiCl as well. They may play a role in formation of conditioned taste aversion.

Central orexin facilitates gastric relaxation and contractility in rats.

The effects of the intracisternal administration of synthetic orexin-A (3 nmol) on gastric motility were examined in rats. The administration of orexin but not a vehicle induced relaxation of the proximal stomach lasting for more than 30 min. Phasic contractions in the distal stomach were facilitated in response to the administration of orexin but not a vehicle. Facilitation in the distal stomach was not observed in the animals which underwent the sectioning of the bilateral vagi at the subdiaphragmatic level. Relaxation of the proximal stomach was observed in vagotomized animals but the magnitude of relaxation was significantly smaller than that in intact animals. These results suggest that central orexin facilitates distal stomach motility and relaxation of the proximal stomach via vagi.

Chemosensitive neurons within the area postrema of the rat

It is demonstrated that some neurons within the area postrema, if not all, are responsive to glucose or sodium ions applied topically by means of microelectro-osmotic techniques. Glucose-responsive neurons displayed a marked decrease in the discharge rate in response to the topical application of glucose. Two different types of sodium-responsive neurons were observed; one was characterized by increasing the frequency of the discharges responding to microiontophoretic application of Na+, while the other showed the opposite response by decreasing the discharge rate in response to the same stimulation. They may serve enteroceptors in response to changes in the glucose or sodium concentrations of cerebrospinal fluid (CSF) or blood.

Projection of nucleus tractus solitarius units influenced by hepatoportal afferent signal to parabrachial nucleus

In urethan-chloralose anesthetized rats, units in the nucleus tractus solitarius (NTS) which antidromically responded to electrical stimulation of the parabrachial nucleus (PB) were investigated for their responses to hepatic-vagal afferent signals. Among 63 NTS units examined, 25 (40%) were excited, 17 (27%) inhibited and the remaining 21 (33%) unaffected by single shock electrical stimulation of the hepatic branch of the vagus nerve. Topical application of Na+ produced an increase in discharge rate of 9 units and a decrease in 5 units. Portal infusion of hypertonic saline produced an increase in discharge rate of 3 units and a decrease in 5 units. Furthermore, 3 units responded to both topical application of Na+ and portal infusion of hypertonic saline.

Fourth ventricular administration of ghrelin induces relaxation of the proximal stomach in the rat

The effects of fourth ventricular administration of ghrelin on motility of the proximal stomach were examined in anesthetized rats. Intragastric pressure (IGP) was measured using a balloon situated in the proximal part of the stomach. Administration of ghrelin into the fourth ventricle induced relaxation of the proximal stomach in a dose-dependent manner. Significant reduction of IGP was observed at doses of 3, 10, or 30 pmol. The administration of ghrelin (10 or 30 pmol) with growth hormone secretagogue receptor (GHS-R) antagonist ([D-Lys3] GHRP-6; 1 nmol) into the fourth ventricle did not induce a significant change in IGP. The sole administration of [D-Lys3] GHRP-6 also did not induce a significant change in IGP. Bilateral sectioning of the vagi at the cervical level abolished the relaxation induced by the administration of ghrelin (10 or 30 pmol) into the fourth ventricle, suggesting that relaxation induced by ghrelin is mediated by vagal preganglionic neurons. Microinjections of ghrelin (200 fmol) into the caudal part of the dorsal vagal complex (DVC) induced obvious relaxation of the proximal stomach. Similar injections into the intermediate part of the DVC did not induce significant change. Dose-response analyses revealed that the microinjection of 2 fmol of ghrelin into the caudal DVC significantly reduced IGP. These results revealed that ghrelin induced relaxation in the proximal stomach via GHS-R situated in the caudal DVC.

Effects of gastric distension and electrical stimulation of dorsomedial medulla on neurons in parabrachial nucleus of rats

The effects of gastric distension and electrical stimulation of the dorsomedial medulla on neurons within the parabrachial nucleus (PB) were investigated electrophysiologically in urethane-chloralose anesthetized rats. Among 74 neurons tested, electrical stimulation of the nucleus of the solitary tract (NTS) excited 30 neurons (excitatory neurons) and inhibited 14 neurons (inhibitory neurons). Fourteen neurons increased and 12 neurons decreased their discharge rates in response to gastric distension. Twenty-two neurons responded to both electrical stimulation of the NTS and gastric distension. Both excitatory and inhibitory neurons showed either an increase or a decrease in discharge rate responding to gastric distension. Furthermore, three neurons that decreased their discharge rates and two neurons that increased their discharge rates during gastric distension also responded to intravenous administration of metaraminol indicating some effect of baroreceptor activation on the neural activity. The responses of another 49 neurons in the PB to electrical stimulation of area postrema and gastric distension were analyzed. Electrical stimulation of the AP excited 14 neurons and inhibited only one neuron. Five neurons increased and seven neurons decreased their discharge rates in response to gastric distension. Only one inhibitory neuron responded to gastric distension. These observations suggested that the PB neurons received gastric mechanoreceptive inputs from the NTS.

Area postrema mediates gastric motor response induced by apomorphine in rats

The effects of apomorphine administration on the autonomic responses were investigated in rats. Distinctive gastric motor responses were observed after the intravenous administration of apomorphine (0.1 mg/kg body weight). Gastric motor responses in the distal stomach induced by apomorphine administration were classified into two types. One type involved inhibition of phasic contractions which appeared just after the administration of apomorphine. The other involved an increase in the frequency of small phasic contractions accompanied by increased gastric tone appearing with a relatively longer delay. No relaxation was observed in either the proximal or distal stomach. These gastric motor responses showed a dose-response effect to the amount of apomorphine administered (0.002-0.1 mg/kg body weight). In addition, submandibular salivary secretion was observed in response to the intravenous administration of apomorphine at a dose of 3 or 10 mg/kg body weight. Pretreatment with domperidone (1 or 2 mg/kg body weight) or the ablation of the area postrema (AP) abolished the gastric motor response and salivary secretion induced by the administration of apomorphine. In conclusion, rats showed definitive autonomic phenomena in response to the administration of apomorphine. Dopamine 2-like receptors situated in the AP mediate apomorphine-induced autonomic phenomena in rats.