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Hypothalamic oxytocin (OXT) has stress-attenuating effects. Social interaction in a positive environment continuously activates OXT release system. We have recently shown that pair housing restores delayed gastric emptying following chronic heterotypic stress, via up-regulation of OXT mRNA expression in rats. We tested the hypothesis that affiliative behavior attenuates stress responses via upregulating OXT expression. Adult male SD rats were divided into two groups: the rat with a stressed partner (RSP) and the rat with a non-stressed partner (RNSP). RSPs were pair housed with a partner that received different types of stress for 7 consecutive days (chronic heterotypic stress). RNSPs were pair housed with a partner who did not receive any stress. After each stress loading, the rats were returned to their home cages and the behaviors of RSPs and RNSPs toward their partners were videotaped. After the study completion, RSPs and RNSPs were loaded with acute restraint stress. Then, gastric emptying and colonic transit were measured. Corticotropin releasing factor (CRF) and OXT expression in the paraventricular nucleus (PVN) were evaluated by real time RT-PCR and immunohistochemistry. The time of affiliative behaviors toward their partners was increased in RSPs, compared to that of RNSPs. Delayed gastric emptying and accelerated colonic transit induced by acute restraint stress were significantly attenuated in RSPs, compared to RNSPs. CRF expression was reduced, while OXT expression was increased in RSPs in response to acute stress, compared to controls. It is suggested that affiliative behaviors may upregulate hypothalamic OXT expression, which in turn attenuates stress responses., (Published by Elsevier B.V.)

Orexin receptor type-1 (OX1R) is expressed in the dorsal motor nucleus of vagi (DMV). Although orexin-A (OXA) plays an important role in mediating stress responses, it remains unclear how central OXA regulates gastric dysmotility induced by stress. Acute restraint stress (ARS) delays solid gastric emptying via the central corticotropin releasing factor (CRF) and peripheral autonomic neural pathways. We have previously shown that ARS impairs postprandial antro-pyloric coordination and delays solid gastric emptying in rats. We also showed that postprandial gastric contractions were augmented in response to ARS in rats. However, the mechanism of augmented postprandial gastric contractions induced by ARS remains unclear. We tested the hypothesis that augmented gastric motility induced by ARS is mediated via the central OX1R. We also assessed the role of endogenous OXA in the mediation of gastric motility under non-stressed conditions in conscious rats. A strain gauge transducer was implanted on the antrum to record postprandial gastric motility. To investigate whether endogenous OXA is involved in ARS-induced augmented gastric motility, selective OX1R antagonist, SB-334867 (16 μg), was administered intracerebroventricularly (icv). Icv-injection of SB-334867 abolished the augmented gastric contractions induced by ARS. Spontaneous postprandial gastric motility was enhanced by icv-injection of OXA (10 μg), while it was attenuated by icv-injection of SB-3334867. It is suggested that central OXA mediates augmented gastric motility induced by ARS in rats. Central OXA also modulates postprandial gastric contractions in non-stressed conditions., (Published by Elsevier Inc.)

Accumulation of daily life stress (chronic stress) often causes functional gastrointestinal diseases. Central oxytocin plays an important role in attenuating stress responses and regulating positive social interactions. Adult male rats were either paired or singly housed 1 week prior to the stress loading. Solid gastric emptying was measured after 7 consecutive days of chronic heterotypic stress. To study whether endogenous oxytocin is involved in restoring the delayed gastric emptying after paired housing, an oxytocin antagonist was injected intracerebroventricularly (icv) before the gastric emptying study. CRF and oxytocin mRNA expression in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) was evaluated by real time RT-PCR. In singly housed rats, chronic heterotypic stress significantly delayed gastric emptying (35.1+/-2.8%, n=6, P

In our daily life, individuals encounter with various types of stress. Accumulation of daily life stress (chronic stress) often causes gastrointestinal symptoms and functional gastrointestinal diseases. Although some can adapt toward chronic stress, the adaptation mechanism against chronic stress remains unknown. Although acute stress delays gastric emptying and alters upper gastrointestinal motility, effects of chronic stress on gastric motility still remain unclear. We investigated the effects of acute (single stress) and chronic (repeated stress for 5 consecutive days) stress on solid gastric emptying and interdigestive gastroduodenal contractions in rats. It is well established that acute restraint stress inhibits solid gastric emptying via central corticotropin-releasing factor (CRF). To investigate whether the sensitivity to CRF is altered following chronic stress, CRF was administered intracisternally. Ghrelin is involved in regulating gastric emptying and upper gastrointestinal motility in rodents. The changes in plasma active ghrelin levels and mRNA expression in the stomach were studied following chronic stress. To evaluate the effects of chronic stress on the hypothalamus-pituitary-adrenal (HPA) axis, plasma corticosterone levels were also measured. Delayed gastric emptying observed in acute stress was completely restored following chronic stress. Acute stress abolished gastric phase III-like contractions, without affecting duodenal phase III-like contractions in the interdigestive state. Impaired gastric phase III-like contractions were also restored following chronic stress. Plasma ghrelin levels and ghrelin mRNA expression were increased significantly after chronic stress. Intracisternal injection of CRF delayed gastric emptying and impaired gastric motility in rats who received chronic stress. Plasma corticosterone concentrations were no more elevated following chronic stress. The restored gastric emptying following chronic stress was antagonized by the administration of ghrelin receptor antagonists. The adaptation mechanism may involve upregulation of ghrelin expression and attenuation of the HPA axis. In contrast, the sensitivity to central CRF remained unaltered following chronic stress in rats.

Acupuncture may modulate the imbalance of the autonomic nervous system. It is well known that restraint stress delays gastric emptying via inhibiting parasympathetic activity and/or stimulating sympathetic activity in rats. We have previously shown that electroacupuncture (EA) improves delayed gastric emptying induced by restraint stress in rats. To investigate whether the beneficial effect of EA on delayed gastric emptying is associated with its modulatory effects on autonomic nervous activity, we utilized spectral analysis of heart rate variability (HRV). In rats, the power in the low frequency (LF; 0.04-1.0 Hz) and high frequency (HF; 1.0-3 Hz) band of HRV represent sympathetic and parasympathetic activities, respectively. Electrocardiography (ECG)-electrodes were implanted on the subcutaneous tissues of the back. One week after the surgery, ECG was recorded before, during and after the restraint stress loading in a conscious state. EA (10 Hz) was applied at bilateral acupuncture points [ST-36 (lower leg) or BL-21 (back)] during restraint stress loading. In response to restraint stress, heart rate and LF component were increased, suggesting the increased activity of sympathetic tone. EA at ST-36 significantly reduced the elevated heart rate and LF, compared to that of control group. EA at ST-36 also significantly increased HF component after finishing the stress loading. In contrast, EA at BL-21 had no significant effect on the heart rate, LF and HF. It is suggested that EA at ST-36 stimulates parasympathetic activity and inhibits sympathetic activity under the restraint stress in rats.

During the early stages of diabetes, gastric emptying is often accelerated, rather than delayed. The mechanism of accelerated gastric emptying in diabetes has not been fully studied. A recent study showed that plasma ghrelin levels were elevated in diabetes. As postprandial antropyloric coordination plays an important role in mediating solid gastric emptying, we hypothesize that the elevated plasma ghrelin levels increase postprandial antropyloric coordination to accelerate emptying in the early stages of diabetes. To test this hypothesis, rats were made diabetic by streptozotocin (STZ; 50 mg/kg) injection, and, 2 wk later, pre- and postprandial plasma ghrelin levels, antropyloric coordination, and solid gastric emptying were determined. In control rats, plasma ghrelin levels were immediately reduced after feeding. In contrast, plasma ghrelin levels remained within the fasted levels in STZ rats after feeding. In STZ rats, gastric emptying was significantly accelerated (77.4 +/- 3.2%, n = 6), compared with that of control rats (58.8 +/- 2.5%, n = 6, P < 0.05). Treatments with anti-ghrelin antibodies attenuated accelerated gastric emptying in STZ rats (50.1 +/- 3.5%, n = 6, P < 0.05), while having little effect in vehicle control rats. The incidence of postprandial antropyloric coordination was significantly increased in STZ rats, compared with that of control rats (P < 0.05). Treatments with anti-ghrelin antibodies suppressed this enhanced antropyloric coordination in STZ rats. Our study suggests that elevated endogenous ghrelin enhances antropyloric coordination, which accelerates gastric emptying in the early stages of diabetes.

Ghrelin is known to enhance gastric motility and accelerate gastric emptying of liquid and solid food in rats. As solid gastric emptying is regulated by the coordinated motor pattern between the antrum and pylorus (antro-pyloric coordination), we studied the correlation between solid gastric emptying and antro-pyloric coordination in response to ghrelin. Rats were given 1.5 g of solid food after a 24-h fasting. Immediately after the ingestion, ghrelin (0.4-8.0 microg/kg) or saline was administered by intraperitoneal (i.p.) injection. Ninety minutes after the feeding, rats were euthanized and gastric content was removed to calculate gastric emptying. To evaluate the antro-pyloric coordination, strain gauge transducers were sutured on the antrum and pylorus. The incidence of postprandial antro-pyloric coordination was compared between ghrelin-and saline-injected rats. In saline-injected rats, gastric emptying was 58.3+/-3.7% (n=6). Ghrelin (4.0-8.0 microg/kg), accelerated gastric emptying. Maximum effect was obtained by ghrelin (4.0 microg/kg), which significantly accelerated gastric emptying to 77.4+/-3.7% (n=6, p<0.05). The number of antro-pyloric coordination 20-40 min after feeding was significantly increased in ghrelin-injected rats, compared to that of saline-injected rats (n=4, p<0.05). It is suggested that enhanced antro-pyloric coordination play an important role in accelerated solid gastric emptying induced by ghrelin.

Acupuncture has been used for treating functional gastrointestinal (GI) disorders. Animal studies have demonstrated that acupuncture antagonized various stress-induced responses. We investigated the effects of electroacupuncture (EA) at ST-36 (Zusanli; lower limb) on stress-induced alteration of GI motor activities. Solid gastric emptying was significantly delayed by restraint stress (29.6+/-2.4%; n=7) compared to that of controls (60.0+/-2.5%; n=8). Delayed gastric emptying was significantly improved by EA at ST-36 (47.2+/-1.8%). Intracisternal (IC) injection of corticotropin releasing factor (CRF; 1 microg) delayed gastric emptying to 25.4+/-3.1%, which was also improved by EA at ST-36, to 53.0+/-7.1% (n=8). The stimulatory effect of EA on stress-induced delayed gastric emptying was abolished by atropine (17.6+/-1.9%) but not by guanethidine (42.2+/-2.3%). Colonic transit was significantly accelerated by restraint stress (GC=7.2+/-0.3; n=8) compared to that of controls (GC=5.2+/-0.2; n=8). Accelerated colonic transit was significantly reduced by EA at ST-36 (GC=4.9+/-0.3). IC injection of CRF accelerated colonic transit (GC=6.9+/-0.2), which was also normalized by EA at ST-36 (GC=4.7+/-0.2). The inhibitory effect of EA on stress-induced acceleration of colonic transit was not affected by guanethidine (GC=4.6+/-0.3). In conclusion, EA at ST-36 showed dual effects: stimulation of stress-induced delayed gastric emptying and inhibition of stress-induced acceleration of colonic transit. The stimulatory effect of EA on stress-induced delayed gastric emptying is mediated via cholinergic pathways. The inhibitory effect of EA on stress-induced acceleration of colonic transit is independent of the sympathetic pathway.

Acupuncture has been used for treating functional gastrointestinal (GI) disorders. Animal studies demonstrated that acupuncture improves various stress-induced physiological responses. We investigated the effects of electroacupuncture (EA) at ST-36 (Zusanli; lower limb) on stress-induced delay of gastric emptying. Solid food gastric emptying in 90 min was significantly delayed by restraint stress (27.3 +/- 2.1%, n = 8), compared to that of controls (64 +/- 2.1%, n = 8). Restraint stress-induced delay of gastric emptying was significantly restored by the intracisternal (IC)-injection of GABA(A) receptor antagonist, bicuculline methiodide (46.5 +/- 3.1%; n = 6) and GABA(B) receptor antagonist, phaclofen (48 +/- 3.3%; n = 6). Delayed gastric emptying induced by restraint stress was significantly improved by EA at ST-36 (49.7 +/- 1.4%). The stimulatory effect of EA on stress-induced delay of gastric emptying was prevented by pretreatment with IC-injection of glutamate receptor antagonist, kynurenic acid (30.1 +/- 2.1%). In conclusion, restraint stress-induced delay of gastric emptying is mediated via central GABA(A) and GABA(B) receptors. EA at ST-36 stimulates glutaminergic neurons in the brainstem resulting in improvement of stress-induced delay of gastric emptying.

Central corticotropin-releasing factor (CRF) plays an important role in mediating restraint stress-induced delayed gastric emptying. However, it is unclear how restraint stress modulates gastric motility to delay gastric emptying. Inasmuch as solid gastric emptying is regulated via antropyloric coordination, we hypothesized that restraint stress impairs antropyloric coordination, resulting in delayed solid gastric emptying in conscious rats. Two strain gauge transducers were sutured onto the serosal surface of the antrum and pylorus, and postprandial gastric motility was monitored before, during, and after restraint stress. Antropyloric coordination, defined as a propagated single contraction from the antrum to the pylorus within 10 s, was followed by > or = 20 s of quiescence. Restraint stress enhanced postprandial gastric motility in the antrum and pylorus to 140 +/- 9% and 134 +/- 9% of basal, respectively (n = 6). The number of episodes of antropyloric coordination before restraint stress, 2.4 +/- 0.4/10 min, was significantly reduced to 0.6 +/- 0.3/10 min by restraint stress. Intracisternal injection of the CRF type 2 receptor antagonist astressin 2B (60 microg) or guanethidine partially restored restraint stress-induced impairment of antropyloric coordination (1.6 +/- 0.3/10 min, n = 6). The restraint stress-induced augmentation of antral and pyloric contractions was increased by astressin 2B and guanethidine but abolished by atropine, hexamethonium, and vagotomy. Restraint stress enhanced postprandial gastric motility via a vagal cholinergic pathway. Restraint stress-induced delay of solid gastric emptying is due to impairment of antropyloric coordination. Restraint stress-induced impairment of antropyloric coordination might be mediated via a central CRF pathway.

Central corticotropin-releasing factor (CRF) delays gastric emptying through the autonomic nervous system. CRF plays an important role in mediating delayed gastric emptying induced by stress. However, it is not clear whether a sympathetic or parasympathetic pathway is involved in the mechanism of central CRF-induced inhibition of solid gastric emptying. The purpose of this study was to investigate whether 1) CRF inhibits solid gastric emptying via a peripheral sympathetic pathway and 2) stress-induced inhibition of solid gastric emptying is mediated via a central CRF and peripheral sympathetic pathways. Using male Sprague-Dawley rats, CRF was injected intracisternally with or without various adrenergic-blocking agents. To investigate whether central CRF-induced inhibition of solid gastric emptying is mediated via a peripheral sympathetic pathway, rats underwent celiac ganglionectomy 1 wk before the gastric emptying study. After solid meal ingestion (90 min), gastric emptying was calculated. To investigate the role of endogenous CRF in stress-induced delayed gastric emptying, a CRF type2 receptor antagonist, astressin2-B, was intracisternally administered. Rats were subjected to a restraint stress immediately after the feeding. Intracisternal injection of CRF (0.1-1.0 microg) dose-dependently inhibited solid gastric emptying. The inhibitory effect of CRF on solid gastric emptying was significantly blocked by guanethidine, propranolol, and celiac ganglionectomy but not by phentolamine. Restraint stress significantly delayed solid gastric emptying, which was improved by astressin2-B, guanethidine, and celiac ganglionectomy. Our research suggests that restraint stress inhibits solid gastric emptying via a central CRF type2 receptor and peripheral sympathetic neural pathway in rats.

The effects of manual acupuncture on gastric motility were investigated in 35 conscious rats implanted with a strain gauge transducer. Twenty (57.1%) rats showed no cyclic groupings of strong contractions (type A), whereas 15 (42.9%) rats showed the phase III-like contractions of the migrating motor complex (type B) in the fasting gastric motility. Acupuncture at the stomach (ST)-36 (Zusanli), but not on the back [Weishu, bladder (BL)-21], increased the peak amplitude of contractions to 172.4 +/- 25.6% of basal in the type A rats (n = 20, P < 0.05). On the other hand, the motility index for 60 min after the acupuncture was not affected by the acupuncture in this group. On the contrary, acupuncture decreased the peak amplitude and motility index to 72.9 +/- 14.0% and 73.6 +/- 16.2% in the type B rats (n = 15, P < 0.05), respectively. The stimulatory and inhibitory effects of acupuncture observed in each type were reproducible on the separate days. In 70% of type A rats, acupuncture induced strong phase III-like contractions lasting for over 3 h that were abolished by atropine, hexamethonium, atropine methyl bromide, and vagotomy. Naloxone significantly shortened the duration of the stimulatory effects from 3.52 +/- 0.21 to 1.02 +/- 0.15 h (n = 3, P < 0.05). These results suggest that acupuncture at ST-36 induces dual effects, either stimulatory or inhibitory, on gastric motility. The stimulatory effects are mediated in part via vagal efferent and opioid pathways.

Delayed gastric emptying has been shown in diabetes. Although it has been proposed that hyperglycemia, and not only autonomic neuropathy, contributes to the pathogenesis of delayed gastric emptying, the inhibitory mechanism of hyperglycemia on gastric emptying remains unclear. We studied the effects of hyperglycemia per se on gastric emptying and postprandial gastric motility in conscious rats. Liquid and solid gastric emptying were compared between saline-infused rats and D-glucose-infused rats. Two strain gauge transducers were implanted on the antrum and pylorus and the postprandial antro-pyloric coordination was compared between euglycemia and hyperglycemia. D-glucose infusion for 30 min increased blood glucose level from 5.4 +/- 0.5 to 13.0 +/- 1.3 mM and significantly delayed gastric emptying. Forty minutes after the feeding, contractions with low frequency (<3 cycles min(-1)) and high amplitude (>15 g) of the antrum were observed. This period reflects the emptying process of the gastric content and the coordination between the antrum and pylorus was frequently observed. D-glucose infusion significantly reduced feeding-induced antral contractions and abolished the number of episodes of antro-pyloric coordination. Sham feeding-induced gastric contractions were also significantly reduced by hyperglycemia. Postprandial antro-pyloric coordination was not observed in vagotomized rats, suggesting a mediation of vagus nerve. It is concluded that hyperglycemia impairs antral contractions and antro-pyloric coordination in rats. The inhibitory effect of hyperglycemia on gastric emptying is mediated, at least in part, via impaired vagal activity.

Objectives: Although it has been demonstrated that hyperglycemia inhibits gastrointestinal (GI) motility, its inhibitory mechanism remains unclear.Design: Electrophysiological study.Settings: As GI motility is under the influence of the vagus, we studied the effects of hyperglycemia on neural activity of the dorsal motor nucleus of vagi (DMV) in anesthetized rats.Measurements and Results: A tungsten electrode was placed in the left side of the DMV area and extracellular electrical signals from the electrode were recorded. Single unit nerve activity was identified by the discriminator. D-glucose infusion elevated the peripheral blood glucose concentration from 3.4-5.9 mm to 12.0-21.8 mm and the neural firing of the DMV was significantly reduced by D-glucose infusion. After the 30 min D-glucose infusion, saline was re-infused for 90 min. Blood glucose level returned to 6.5-7.8 m m and the neural firing partially recovered 90 min after the saline re-infusion. There was a significant negative correlation observed between the counts of neural spikes and blood glucose concentrations ( r=0.84, p<0.01).Conclusion: It is suggested that hyperglycemia impairs GI motility by inhibiting vagal efferent activity. A recent study in intensive care unit (ICU) patients demonstrated that uncontrolled hyperglycemia is associated with poor outcomes. We propose that glycemia control is crucial in ICU patients to maintain the GI motility and vagus nerve activity. [ABSTRACT FROM AUTHOR]

Abstract: Early life stress has been implicated as a risk factor for functional gastrointestinal (GI) disorders. Hypothalamic oxytocin (OXT) is well known to regulate social interactions and affiliative behaviors. We have shown that maternal separation (MS) induces GI dysmotility and impair hypothalamic OXT expression in response to chronic homotypic stress (CHS). We studied whether social interaction can improve GI dysmotility and OXT expression in MS rats. Male neonatal SD rats were exposed to MS for 180min from postnatal day (PND)-2 to PND-14. After weaning, 3MS rats were housed together (pure MS). In another group, 1MS rat was housed with 2 control rats (mixed MS). Anxiety-like behaviors were evaluated in elevated plus maze (EPM). Solid gastric emptying (GE) and colonic transit (CT) were measured following CHS loading. Expression of corticotropin releasing factor (CRF) and OXT in the paraventricular nucleus (PVN) were evaluated by real time RT-PCR and immunohistochemistry. Pure MS rats demonstrated increased anxiety-like behaviors, which were significantly reduced in mixed MS rats. Delayed GE (31.5±2.8%, n=6) and accelerated CT [Geometric center (GC) =8.9±0.8, n=6] observed in pure MS rats were restored in mixed MS rats (GE=67.8±3.8%, GC=6.7±1.2, n=6, P<0.05) following CHS. OXT mRNA expression was upregulated, while CRF mRNA expression was downregulated in mixed MS rats, compared to pure MS rats. The number of OXT-immunoreactive cells was significantly increased following CHS at the PVN in mixed MS rats. Our study may contribute to the treatment strategies for GI motility disorders associated with early life stress. [Copyright &y& Elsevier]

Abstract: We have previously shown that the elevated plasma ghrelin accelerate emptying in the early stage of diabetes in rats. However, it remains unknown whether plasma ghrelin levels are still elevated in the late stage of diabetes. We studied whether solid gastric emptying and plasma ghrelin levels are altered 2–8 weeks after streptozotocin (STZ) injection. The development of autonomic neuropathy was evaluated by spectral analysis of heart rate variability (HRV). Gastric emptying was not different between control and diabetic rats at 4 weeks and 6 weeks, while it delayed at 8 weeks in STZ rats. The pre-prandial ghrelin levels were not significantly different between control and diabetic rats at 4–8 weeks. In control rats, the plasma ghrelin levels were significantly reduced 30min after the feeding at 4–8 weeks. In contrast, there was no significant reduction of ghrelin levels observed in diabetic rats at 4–8 weeks. Plasma insulin levels were significantly increased 30min after feeding in control rats, but not STZ rats, at 4–8 weeks. Both HF (parasympathetic activity) and LF (sympathetic activity) component were gradually reduced 6–8 weeks after STZ injection. It is suggested that hypoinsulinemia associated with diabetes increases plasma ghrelin levels. At the late stage of diabetes, gastric emptying is delayed despite increased plasma ghrelin levels. The delayed gastric emptying is mainly due to impaired activity of autonomic nerves at the late stage of diabetes. [Copyright &y& Elsevier]

Abstract: Acute restraint stress delays gastric emptying and accelerates colonic transit via central corticotropin releasing factor (CRF) in rats. In contrast, central oxytocin has anxiolytic effects and attenuates the hypothalamus–pituitary–adrenal (HPA) axis in response to stress. Our recent study showed that up regulated oxytocin expression attenuates hypothalamic CRF expression and restores impaired gastric motility following chronic homotypic stress in mice. We studied the effects of acute and chronic homotypic stress on colonic transit and hypothalamic CRF mRNA expression in wild type (WT) and oxytocin knockout (OXT-KO) mice. Colonic transit was measured following acute restraint stress or chronic homotypic stress (repeated restraint stress for 5 consecutive days). 51Cr was injected via a catheter into the proximal colon. Ninety minutes after restraint stress loading, the entire colon was removed. The geometric center (GC) was calculated to evaluate colonic transit. Expression of CRF mRNA in the supraoptic nucleus (SON) was measured by real time RT-PCR. Colonic transit was significantly accelerated following acute stress in WT (GC=8.1±0.8; n =7) and OXT KO mice (GC=9.4±0.3; n =7). The accelerated colonic transit was significantly attenuated in WT mice (GC=6.6±0.5; n =9) following chronic homotypic stress while it was still accelerated in OXT KO mice (GC=9.3±0.5; n =8). The increase in CRF mRNA expression at the SON was much greater in OXT-KO mice, compared to WT mice following chronic homotypic stress. It is suggested that oxytocin plays a pivotal role in mediating the adaptation mechanism following chronic homotypic stress in mice. [Copyright &y& Elsevier]

Abstract: Centrally released oxytocin (OXT) has anxiolytic and anti-stress effects. Delayed gastric emptying (GE) induced by acute restraint stress (ARS) for 90min is completely restored following 5 consecutive days of chronic homotypic restraint stress (CHS), via up-regulating hypothalamic OXT expression in rats. However, the mechanism behind the restoration of delayed GE following CHS remains unclear. Gamma-aminobutyric acid (GABA)-projecting neurons in the paraventricular nucleus (PVN) have been shown to inhibit corticotropin releasing factor (CRF) synthesis via GABAA receptors. We hypothesized that GABAA receptors are involved in mediating the inhibitory effect of OXT on CRF expression in the PVN, which in turn restores delayed GE following CHS. OXT (0.5μg) and selective GABAA receptor antagonist, bicuculline methiodide (BMI) (100ng), were administered intracerebroventricularly (icv). Solid GE was measured under non-stressed (NS), ARS and CHS conditions. Expression of CRF mRNA in the PVN was evaluated by real time RT-PCR. Neither OXT nor BMI changed GE and CRF mRNA expression under NS conditions. Delayed GE and increased CRF mRNA expression induced by ARS were restored by icv-injection of OXT. The effects of OXT on delayed GE and increased CRF mRNA expression in ARS were abolished by icv-injection of BMI. Following CHS, delayed GE was completely restored in saline (icv)-injected rats, whereas daily injection of BMI (icv) attenuated the restoration of delayed GE. Daily injection of BMI (icv) significantly increased CRF mRNA expression following CHS. It is suggested that central OXT inhibits ARS-induced CRF mRNA expression via GABAA receptors in the PVN. GABAergic system is also involved in OXT-mediated adaptation response of delayed GE under CHS conditions. [Copyright &y& Elsevier]

Abstract: Restraint stress delays gastric emptying via uncoordinated motility pattern in rats. Central oxytocin has anxiolytic effects and attenuates the hypothalamic-pituitary-adrenal (HPA) axis in response to stress and facilitates stress-induced delayed gastric emptying. However, the role of central oxytocin in regulating gastric motility remains unknown. Postprandial gastric motility was recorded via a strain-gauge transducer, implanted on the antrum in Sprague–Dawley (SD) rats. To investigate whether central and peripheral oxytocin are involved in gastric motility, oxytocin (10μg) was administered intracerebroventricularly (icv) and intraperitoneally (ip). Central and peripheral oxytocin administration did not affect the postprandial gastric motility under non-stressed conditions. Restraint stress augmented gastric contractions. Central administration of oxytocin, but not peripheral administration, abolished the augmented postprandial gastric contractions induced by restraint stress. Oxytocin facilitates stress-induced delayed gastric emptying via alleviating uncoordinated gastric motility. Oxytocin might be a candidate for the treatment of stress-induced GI motility disorders. [Copyright &y& Elsevier]