Nucleus Raphe Obscurus

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Z K Krowicki - One of the best experts on this subject based on the ideXlab platform.

  • opposing effects of vasoactive intestinal polypeptide on gastric motor function in the dorsal vagal complex and the Nucleus Raphe Obscurus of the rat
    Journal of Pharmacology and Experimental Therapeutics, 1997
    Co-Authors: Z K Krowicki, Nicole A Nathan, Pamela J Hornby
    Abstract:

    Vasoactive intestinal polypeptide (VIP)-like immunoreactive cell bodies and fibers and VIP binding sites exist in the brainstem nuclei that regulate autonomic function. Therefore, we investigated the effects of microinjection of VIP in the dorsal vagal complex (DVC), Nucleus Raphe Obscurus (nROb) and Nucleus ambiguus of alpha-chloralose-anesthetized rats while recording intragastric pressure, pyloric and greater curvature smooth muscle contractile activity, blood pressure and heart rate. Microinjection of VIP into the DVC increased intragastric pressure (1-100 pmol) and pyloric smooth muscle contractile activity (100 pmol), as well as arterial blood pressure (1-100 pmol). Whereas VIP microinjected into the nROb (10-100 pmol) decreased intragastric pressure and inhibited pyloric smooth muscle contractile activity. Mean arterial blood pressure increased in response to VIP in the nROb at the highest dose of 100 pmol only. No changes in gastric motor and cardiovascular function were noted after microinjection of VIP (1-100 pmol) into the region of the Nucleus ambiguus. The gastric motor effects of VIP in the DVC (10 pmol) and nROb (50 pmol) were completely abolished by bilateral cervical vagotomy. These data show that VIP may produce opposite vagally mediated gastric motor responses upon its microinjection into the DVC and nROb.

  • Bicuculline blocks the inhibitory effects of substance p but not vasoactive intestinal polypeptide on gastric motor function in the Nucleus Raphe Obscurus of the rat
    InflammoPharmacology, 1997
    Co-Authors: Z K Krowicki, P. J. Hornby
    Abstract:

    We have shown previously that substance P (SP) and vasoactive intestinal polypeptide (VIP), microinjected into the caudal Nucleus Raphe Obscurus (nROb) of the rat decreases intragastric pressure via vagally mediated pathways. Since γ-aminobutyric acid (GABA) is a transmitter of interneurons innervating non-adrenergic, non-cholinergic pathways that modulate gastric peristalsis, we tested the hypothesis that peripheral GABA is a mediator of inhibitory effects of SP and VIP in the nROb on gastric motor function. Substance P (135 pmol) or VIP (100 pmol) were microinjected into the nROb of the same α-chloralose-anaesthetized rats before and 60 min after peripheral administration of bicuculline methiodide (0.4 mg/kg sc), a GABA_A receptor antagonist. As expected, both SP and VIP, microinjected into the nROb, evoked marked decreases in intragastric pressure before bicuculline. However, the gastric motor effects of SP, but not VIP, were abolished by bicuculline. Therefore we conclude that SP-evoked gastric relaxation in the nROb is mediated through a peripheral GABA-ergic pathway.

  • the inhibitory effect of substance p on gastric motor function in the Nucleus Raphe Obscurus is mediated via nitric oxide in the dorsal vagal complex
    Journal of The Autonomic Nervous System, 1996
    Co-Authors: Z K Krowicki, Pamela J Hornby
    Abstract:

    Abstract We have previously shown that substance P (SP), microinjected into the caudal Nucleus Raphe Obscurus (nROb) of the rat decreases intragastric pressure via a vagally mediated pathway. Recent studies from this laboratory demonstrated that nitric oxide (NO) synthase is present in the dorsal vagal complex (DVC) and NO synthase blockade in the DVC of the rat with N G -nitro- l -arginine methyl ester ( l -NAME) evokes increases in intragastric pressure. Since the nROb controls gastric vagal outflow through the DVC, we tested the hypothesis that NO in the DVC is a mediator of inhibitory effects of SP on gastric motor function in the nROb. Substance P (135 pmol) was microinjected into the nROb 3–6 min after bilateral microinjections of l -NAME (45 nmol per site) into the DVC of chloraloseanesthetized rats were started. Changes in the area of the response for intragastric pressure on microinjection of SP after l -NAME did not differ from the effect of vehicle microinjected after l -NAME and were significantly lower when compared with the effect of SP microinjected after vehicle. We conclude that SP in the nROb releases NO in the DVC to mediate the inhibitory effect on intragastric pressure.

  • the Nucleus Raphe Obscurus controls pancreatic hormone secretion in the rat
    American Journal of Physiology-endocrinology and Metabolism, 1995
    Co-Authors: Z K Krowicki, Pamela J Hornby
    Abstract:

    Until recently, the dorsal vagal complex (DVC) was considered as the only brain stem regulatory center for the vagal control of the endocrine pancreas. Because the Nucleus Raphe Obscurus (NRO) maintains anatomic connections via the DVC to the pancreas, a functional significance of these findings was investigated in the present study. Kainic acid and vehicle were microinjected into the right DVC and the NRO of alpha-chloralose-anesthetized rats, and plasma concentrations of rat insulin, glucagon, and glucose were determined before and 5, 15, 30, and 60 min after injections. Chemical stimulation of neurons in the DVC by kainic acid at a dose of 200 pmol evoked increases in concentrations of insulin, with a peak at 15 min, and glucagon, with a peak at 30 min. Microinjection of kainic acid into the NRO at a dose of 200 pmol, but not at a dose of 20 pmol, produced increases in plasma concentrations of insulin, with a peak at 30 min, and glucagon, with a peak at 60 min. Plasma glucose levels on microinjection of kainic acid into the NRO at a dose of 20 pmol were decreased, whereas no changes on microinjection of kainic acid at a dose of 200 pmol were observed. The effects of kainic acid on insulin and glucagon secretion in the NRO were abolished by bilateral vagotomy. The study demonstrates for the first time that the NRO can contribute to vagal control of pancreatic endocrine function, although the exact circuitry and neurotransmitters involved in this response remain unknown.

  • serotonin and thyrotropin releasing hormone do not augment their effects on gastric motility on their microinjection into the Nucleus Raphe Obscurus of the rat
    Journal of Pharmacology and Experimental Therapeutics, 1995
    Co-Authors: Z K Krowicki, P. J. Hornby
    Abstract:

    The existence of an interaction between serotonin (5-HT) and thyrotropin-releasing hormone (TRH) in the Nucleus Raphe Obscurus (NRO) of the rat in their excitatory effects on gastric motor function was examined using two different approaches. First, 5-HT and TRH were microinjected into the NRO alone at two different doses and then as a mixture in the same animals. In a second group of animals, both agents were microinjected in a rapid (20-30-sec interval) sequential order. These experiments were performed in alpha-chloralose-anesthetized rats intragastric pressure and pyloric and greater curvature motility were monitored. Both 5-HT at a dose of 6 nmol and TRH at doses of 0.6 and 15 pmol evoked significant increases in intragastric pressure. Microinjection of a mixture of 5-HT at a low dose of 0.6 nmol and TRH at doses of 0.6 pmol (low) and 15 pmol (high) resulted in significant increases in intragastric pressure that did not differ from the effects of TRH microinjected alone. A mixture of 5-HT at a low dose of 0.6 nmol and TRH at a high dose of 15 pmol evoked increases in pyloric motility that did not differ from the effects of TRH alone and increases in greater curvature motility that were significantly lower than the effects of TRH alone at the same dose. Microinjection of a mixture of 5-HT at a high dose of 6 nmol and TRH at a low dose of 0.6 pmol evoked increases in intragastric pressure that did not differ from the effect of 5-HT alone. Rapid sequential microinjection of TRH at either a low dose of 0.6 pmol or the larger dose of 15 pmol after 5-HT (0.6 nmol) resulted in increases in intragastric pressure that did not differ from the response to either dose of TRH microinjected after vehicle. Similarly, the intragastric pressure response to 5-HT (0.6 nmol) given after either dose of TRH was not significantly different from the response to 5-HT after vehicle. In summary, our study demonstrates that 5-HT and TRH do not augment their excitatory effects on gastric motor function on dual or sequential micro-injections in the NRO of the alpha-chloralose-anesthetized rats.

Pamela J Hornby - One of the best experts on this subject based on the ideXlab platform.

  • opposing effects of vasoactive intestinal polypeptide on gastric motor function in the dorsal vagal complex and the Nucleus Raphe Obscurus of the rat
    Journal of Pharmacology and Experimental Therapeutics, 1997
    Co-Authors: Z K Krowicki, Nicole A Nathan, Pamela J Hornby
    Abstract:

    Vasoactive intestinal polypeptide (VIP)-like immunoreactive cell bodies and fibers and VIP binding sites exist in the brainstem nuclei that regulate autonomic function. Therefore, we investigated the effects of microinjection of VIP in the dorsal vagal complex (DVC), Nucleus Raphe Obscurus (nROb) and Nucleus ambiguus of alpha-chloralose-anesthetized rats while recording intragastric pressure, pyloric and greater curvature smooth muscle contractile activity, blood pressure and heart rate. Microinjection of VIP into the DVC increased intragastric pressure (1-100 pmol) and pyloric smooth muscle contractile activity (100 pmol), as well as arterial blood pressure (1-100 pmol). Whereas VIP microinjected into the nROb (10-100 pmol) decreased intragastric pressure and inhibited pyloric smooth muscle contractile activity. Mean arterial blood pressure increased in response to VIP in the nROb at the highest dose of 100 pmol only. No changes in gastric motor and cardiovascular function were noted after microinjection of VIP (1-100 pmol) into the region of the Nucleus ambiguus. The gastric motor effects of VIP in the DVC (10 pmol) and nROb (50 pmol) were completely abolished by bilateral cervical vagotomy. These data show that VIP may produce opposite vagally mediated gastric motor responses upon its microinjection into the DVC and nROb.

  • the inhibitory effect of substance p on gastric motor function in the Nucleus Raphe Obscurus is mediated via nitric oxide in the dorsal vagal complex
    Journal of The Autonomic Nervous System, 1996
    Co-Authors: Z K Krowicki, Pamela J Hornby
    Abstract:

    Abstract We have previously shown that substance P (SP), microinjected into the caudal Nucleus Raphe Obscurus (nROb) of the rat decreases intragastric pressure via a vagally mediated pathway. Recent studies from this laboratory demonstrated that nitric oxide (NO) synthase is present in the dorsal vagal complex (DVC) and NO synthase blockade in the DVC of the rat with N G -nitro- l -arginine methyl ester ( l -NAME) evokes increases in intragastric pressure. Since the nROb controls gastric vagal outflow through the DVC, we tested the hypothesis that NO in the DVC is a mediator of inhibitory effects of SP on gastric motor function in the nROb. Substance P (135 pmol) was microinjected into the nROb 3–6 min after bilateral microinjections of l -NAME (45 nmol per site) into the DVC of chloraloseanesthetized rats were started. Changes in the area of the response for intragastric pressure on microinjection of SP after l -NAME did not differ from the effect of vehicle microinjected after l -NAME and were significantly lower when compared with the effect of SP microinjected after vehicle. We conclude that SP in the nROb releases NO in the DVC to mediate the inhibitory effect on intragastric pressure.

  • the Nucleus Raphe Obscurus controls pancreatic hormone secretion in the rat
    American Journal of Physiology-endocrinology and Metabolism, 1995
    Co-Authors: Z K Krowicki, Pamela J Hornby
    Abstract:

    Until recently, the dorsal vagal complex (DVC) was considered as the only brain stem regulatory center for the vagal control of the endocrine pancreas. Because the Nucleus Raphe Obscurus (NRO) maintains anatomic connections via the DVC to the pancreas, a functional significance of these findings was investigated in the present study. Kainic acid and vehicle were microinjected into the right DVC and the NRO of alpha-chloralose-anesthetized rats, and plasma concentrations of rat insulin, glucagon, and glucose were determined before and 5, 15, 30, and 60 min after injections. Chemical stimulation of neurons in the DVC by kainic acid at a dose of 200 pmol evoked increases in concentrations of insulin, with a peak at 15 min, and glucagon, with a peak at 30 min. Microinjection of kainic acid into the NRO at a dose of 200 pmol, but not at a dose of 20 pmol, produced increases in plasma concentrations of insulin, with a peak at 30 min, and glucagon, with a peak at 60 min. Plasma glucose levels on microinjection of kainic acid into the NRO at a dose of 20 pmol were decreased, whereas no changes on microinjection of kainic acid at a dose of 200 pmol were observed. The effects of kainic acid on insulin and glucagon secretion in the NRO were abolished by bilateral vagotomy. The study demonstrates for the first time that the NRO can contribute to vagal control of pancreatic endocrine function, although the exact circuitry and neurotransmitters involved in this response remain unknown.

  • substance p and serotonin independently affect intragastric pressure when microinjected into the Nucleus Raphe Obscurus of the rat
    Journal of The Autonomic Nervous System, 1995
    Co-Authors: Z K Krowicki, Pamela J Hornby
    Abstract:

    Abstract We have recently shown that microinjection of substance P (SP) into the Nucleus Raphe Obscurus (NRO) of the rat decreases intragastric pressure, whereas microinjection of serotonin (5-HT) increases it. The purpose of the present study was to investigate whether there exists a functional interaction between SP and 5-HT in the NRO of the rat in their effects on gastric motor function. This was accomplished by microinjection of SP (135 pmol) and 5-HT (0.6 and 6 nmol) into the NRO in a rapid, sequential order in α-chloralose-anesthetized rats, while monitoring intragastric pressure and pyloric and greater curvature motilities. Substance P evoked significant decreases in intragastric pressure when microinjected into the NRO after vehicle and after 5-HT (at both 0.6 and 6 nmol). There was no difference in the magnitude of the SP effect after 5-HT when compared to the response after vehicle. Serotonin at a dose of 6 nmol, but not at a dose of 0.6 nmol, elicited significant increases in intragastric pressure when microinjected after vehicle or after SP, and there was no difference between the responses to 5-HT with respect to the initial treatment. We conclude that SP and 5-HT act independently in the NRO of the rat to affect intragastric pressure.

  • trh and substance p independently affect gastric motility in Nucleus Raphe Obscurus of the rat
    American Journal of Physiology-gastrointestinal and Liver Physiology, 1994
    Co-Authors: Z K Krowicki, Pamela J Hornby
    Abstract:

    The purpose of this study was to investigate whether there exists a functional interaction between thyrotropin-releasing hormone (TRH) and substance P (SP) in the Nucleus Raphe Obscurus (NRO) in their effects on gastric motor function. This was accomplished by microinjection of TRH (6-45 pmol) and SP (10 and 135 pmol) into the NRO alone and then either as a mixture or in rapid sequential order in alpha-chloralose-anesthetized rats, while intragastric pressure and pyloric and greater curvature motility were monitored. TRH (15 and 45 pmol) evoked significant increases in gastric motor activity, whereas SP (135 pmol) elicited decreases in intragastric pressure. SP at a dose of 10 pmol was ineffective alone in altering gastric motor function. Microinjection of a mixture of TRH (15 pmol) and SP (10 pmol) into the NRO resulted in significant increases in intragastric pressure, pyloric motility, and greater curvature motility; these changes in gastric motor function were similar to the effect of TRH (15 pmol) alone. A mixture of TRH (15 pmol) and SP (135 pmol) resulted in changes in gastric motor activity that were significantly less than the effect of TRH (15 pmol) microinjected into the NRO alone and appeared to be an additive effect of each peptide. The results of sequential microinjections of both peptides were consistent with these findings. The stimulative effect of TRH (15 and 45 pmol) on intragastric pressure, microinjected into the NRO 30 s after SP (135 pmol), did not differ from the effect of TRH microinjected at the same doses after vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Michael S Beattie - One of the best experts on this subject based on the ideXlab platform.

  • dissociation of the effects of Nucleus Raphe Obscurus or rostral ventrolateral medulla lesions on eliminatory and sexual reflexes
    Physiology & Behavior, 2002
    Co-Authors: Gregory M Holmes, Gerlinda E Hermann, Richard C Rogers, Jacqueline C Bresnahan, Michael S Beattie
    Abstract:

    Rat preparations were used to investigate long-term changes in external anal sphincter (EAS) contractions and reflexive penile erection following electrolytic lesions of the Nucleus Raphe Obscurus (nRO) or the rostral ventrolateral medulla. EAS contractions were measured electromyographically (EAS EMG) following distention of the EAS with a 5-mm probe. Penile erections were measured using a standard ex copula reflex testing paradigm. At 48 h postlesion, 100% of nRO-lesioned animals displayed reflexive erections and the magnitude of EAS EMG was significantly greater in lesioned animals than in sham controls. These results suggested EAS hyperreflexia following destruction of the nRO. By 14 days postlesion, EAS responsiveness in nRO-lesioned animals had returned to levels comparable to nonlesioned animals. No measures of penile erection were affected by nRO lesions. In animals with Nucleus gigantocellularis (Gi) and lateral Nucleus paragigantocellularis (Gi-lPGi) lesions, no significant changes to EAS reflexes were observed at any time point. At 48 h postoperative, Gi-lPGi lesions significantly reduced the latency to first erection and increased the number of erections elicited relative to controls. Similar facilitation of erection latency was observed at 14 days postlesion, while erection number and flip total were no longer significantly different from controls. These and previous studies suggest that the nRO regulates defecatory reflexes in the rat. These data further suggest that the comingled EAS and bulbospongiosus (BS) motoneurons are controlled by discrete and separate brainstem circuits and that increases in EAS and penile reflexes after spinal cord lesions are mediated by loss of different descending inputs.

  • descending projections from the Nucleus Raphe Obscurus to pudendal motoneurons in the male rat
    The Journal of Comparative Neurology, 1998
    Co-Authors: Gerlinda E Hermann, Richard C Rogers, Gregory M Holmes, Jacqueline C Bresnahan, Michael S Beattie
    Abstract:

    Previous physiological and behavioral studies have shown that the Nucleus Raphe Obscurus (nRO) modulates pelvic floor reflex function (Yamanouchi and Kakeyama [1992] Physiol. Behav. 51:575–579; Beattie et al. [1996] Soc. Neurosci. Abstr. 22:722.4; Holmes et al. [1997] Brain Res. 759:197–204). In the present study, small injections of fluorescent tracers were used to investigate direct descending projections from the rostral and caudal portions of the brainstem nRO to retrogradely labeled pudendal motoneurons (MN) in the male rat. The caudal nRO projects into the ventral and lateral funiculi of the spinal cord, with arborizations in the thoracic intermediolateral cell column; in laminae VII, IX, and X of the lumbosacral cord; and in the sacral parasympathetic Nucleus (SPN). Many identified external anal sphincter and ischiocavernosus MNs appeared to be in direct apposition with fibers originating from the caudal nRO; and more than half of the bulbospongiosus MNs that were identified appeared to receive such descending input. In addition to the nRO spinal autonomic and pudendal motoneuronal targets, projections were observed to regions of the intermediate gray that contain interneurons organizing the pelvic floor reflexes and to MN pools that are involved in functionally related somatic activities. Finally, several neurons in the lumbar enlargement were labeled retrogradely with FluoroRuby after injections into the nRO and the immediately adjacent reticular formation. Thus, the nRO may be in a position to modulate the coordinated actions of autonomic preganglionic and functionally related skeletal MN activity involved in sexual and eliminative reflex functions. J. Comp. Neurol. 397:458–474, 1998. © 1998 Wiley-Liss, Inc.

  • Nucleus Raphe Obscurus nro regulation of anorectal motility in rats
    Brain Research, 1997
    Co-Authors: Gregory M Holmes, Gerlinda E Hermann, Richard C Rogers, J M Martau, Jacqueline C Bresnahan, Michael S Beattie
    Abstract:

    Previous research has demonstrated that anorectal contractions in the rat are modulated by activation of spinal autonomic circuits. In the present study, anterograde tracing of descending pathways originating from the caudal Nucleus Raphe Obscurus (nRO) revealed that this Nucleus projects to cells within the intermediolateral (IML) cell column of the thoracic cord and the sacral parasympathetic Nucleus (SPN). These anatomical studies suggested that the nRO may influence the regulation of spinal reflexes of the pelvic floor. In a second set of experiments, acute rat preparations were used to investigate changes in anorectal motility during electrical stimulation of the nRO. Anorectal contractions were measured by a fluid-filled manometer. Electrical stimulation of the nRO significantly reduced spontaneous anorectal activity when compared to baseline contractions recorded for 1 min prior to stimulation. Stimulation sites outside the nRO did not affect anorectal contractions when compared to either (a) the 1-min pre-stimulation baseline for that site or (b) the 1-min stimulation period for sites within the nRO. Stimulation of caudal portions of the nRO were more likely than the rostral nRO to reduce anorectal contractions. Given that the SPN contains preganglionic neurons which may be involved in control of anorectal contractions (mediated via the pelvic nerve), the studies presented here suggest a functional role for nRO regulation of preganglionic motoneurons innervating the distal gut of the rat.

T A Lovick - One of the best experts on this subject based on the ideXlab platform.

  • role of the Nucleus Raphe Obscurus in the inhibition of rostral ventrolateral medullary neurones induced by stimulation in the ventrolateral periaqueductal grey matter of the rabbit
    Neuroscience Letters, 1994
    Co-Authors: Yuqiu Zhang, T A Lovick
    Abstract:

    Abstract Experiments have been carried out to investigate the pathways which mediate the inhibitory influence of the ventrolateral periaqueductal grey matter (vlatPAG) on neurones in the rostral ventrolateral medulla (RVLM). In anaesthetized rabbits, 20-ms trains of electrical stimulation in the vlatPAG inhibited ongoing activity of neurones in the RVLM to n = 9) or 0.2 M glycine ( n = 4) into Nucleus Raphe Obscurus (NRO). We suggest that the inhibitory influence of the vlatPAG on neurones in the RVLM is mediated by a relay in NRO.

  • projections from Nucleus Raphe Obscurus to the periaqueductal grey matter in the rat
    Neuroscience Letters, 1994
    Co-Authors: F M Semenenka, Bridget M Lumb, T A Lovick
    Abstract:

    Retrograde transport of rhodamine- or coumarin-labelled latex microspheres was used to investigate projections from Nucleus Raphe Obscurus (NRO) to the periaqueductal grey matter (PAG) in rats. Few labelled neurones (3.5 +/- 1.2; mean +/- S.E.M.) were seen in NRO after injections of microspheres into the dorsolateral and lateral PAG (n = 11) but after injections into the ventrolateral sector (n = 9), significant numbers (42.6 +/- 8.1) were present, particularly in the rostral third of NRO (66% of labelled cells). The results suggest that the projection from NRO to the PAG is restricted to the ventrolateral sector. Any influence of NRO on the dorsal PAG must therefore be mediated indirectly.

  • serotonergic influence from Nucleus Raphe Obscurus on neurones in the periaqueductal grey matter in the rat
    Brain Research, 1993
    Co-Authors: T A Lovick
    Abstract:

    In rats anaesthetised with urethane, iontophoretic application of 5-hydroxytryptamine (5-HT, 5-70 nA) produced changes in ongoing activity of 41/44 neurones in the periaqueductal grey matter (PAG). The majority (85%) of responsive cells were inhibited and 15% were excited. The inhibitions were mimicked in 5/7 cells by iontophoresis of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 10-30 nA) whilst excitation was produced in 3/5 cells by iontophoresis of the 5-HT2 agonist alpha-methyl-5-HT (10-30 nA). Selective activation of neuronal perikarya in Nucleus Raphe Obscurus (NRO) by microinjection of 50-100 nl D,L-homocysteic acid (DLH) inhibited ongoing activity of 25/31 neurones tested in the PAG for periods of 30-580 s, mean 183.5 s. The duration of the inhibition was potentiated by between 36 and 300% during iontophoresis of the 5-HT re-uptake blocker paroxetine (1-25 nA, 6/6 cells). The results indicate that there is an extensive inhibitory serotonergic input to the PAG which originates, at least in part, from NRO.

P. J. Hornby - One of the best experts on this subject based on the ideXlab platform.

  • Bicuculline blocks the inhibitory effects of substance p but not vasoactive intestinal polypeptide on gastric motor function in the Nucleus Raphe Obscurus of the rat
    InflammoPharmacology, 1997
    Co-Authors: Z K Krowicki, P. J. Hornby
    Abstract:

    We have shown previously that substance P (SP) and vasoactive intestinal polypeptide (VIP), microinjected into the caudal Nucleus Raphe Obscurus (nROb) of the rat decreases intragastric pressure via vagally mediated pathways. Since γ-aminobutyric acid (GABA) is a transmitter of interneurons innervating non-adrenergic, non-cholinergic pathways that modulate gastric peristalsis, we tested the hypothesis that peripheral GABA is a mediator of inhibitory effects of SP and VIP in the nROb on gastric motor function. Substance P (135 pmol) or VIP (100 pmol) were microinjected into the nROb of the same α-chloralose-anaesthetized rats before and 60 min after peripheral administration of bicuculline methiodide (0.4 mg/kg sc), a GABA_A receptor antagonist. As expected, both SP and VIP, microinjected into the nROb, evoked marked decreases in intragastric pressure before bicuculline. However, the gastric motor effects of SP, but not VIP, were abolished by bicuculline. Therefore we conclude that SP-evoked gastric relaxation in the nROb is mediated through a peripheral GABA-ergic pathway.

  • serotonin and thyrotropin releasing hormone do not augment their effects on gastric motility on their microinjection into the Nucleus Raphe Obscurus of the rat
    Journal of Pharmacology and Experimental Therapeutics, 1995
    Co-Authors: Z K Krowicki, P. J. Hornby
    Abstract:

    The existence of an interaction between serotonin (5-HT) and thyrotropin-releasing hormone (TRH) in the Nucleus Raphe Obscurus (NRO) of the rat in their excitatory effects on gastric motor function was examined using two different approaches. First, 5-HT and TRH were microinjected into the NRO alone at two different doses and then as a mixture in the same animals. In a second group of animals, both agents were microinjected in a rapid (20-30-sec interval) sequential order. These experiments were performed in alpha-chloralose-anesthetized rats intragastric pressure and pyloric and greater curvature motility were monitored. Both 5-HT at a dose of 6 nmol and TRH at doses of 0.6 and 15 pmol evoked significant increases in intragastric pressure. Microinjection of a mixture of 5-HT at a low dose of 0.6 nmol and TRH at doses of 0.6 pmol (low) and 15 pmol (high) resulted in significant increases in intragastric pressure that did not differ from the effects of TRH microinjected alone. A mixture of 5-HT at a low dose of 0.6 nmol and TRH at a high dose of 15 pmol evoked increases in pyloric motility that did not differ from the effects of TRH alone and increases in greater curvature motility that were significantly lower than the effects of TRH alone at the same dose. Microinjection of a mixture of 5-HT at a high dose of 6 nmol and TRH at a low dose of 0.6 pmol evoked increases in intragastric pressure that did not differ from the effect of 5-HT alone. Rapid sequential microinjection of TRH at either a low dose of 0.6 pmol or the larger dose of 15 pmol after 5-HT (0.6 nmol) resulted in increases in intragastric pressure that did not differ from the response to either dose of TRH microinjected after vehicle. Similarly, the intragastric pressure response to 5-HT (0.6 nmol) given after either dose of TRH was not significantly different from the response to 5-HT after vehicle. In summary, our study demonstrates that 5-HT and TRH do not augment their excitatory effects on gastric motor function on dual or sequential micro-injections in the NRO of the alpha-chloralose-anesthetized rats.