Stimulation Of Medullary Raphe Nuclei Research Articles

Thyrotropin-releasing hormone analog injected into the raphe pallidus and obscurus increases gastric contractility in rats

The present study was performed to investigate the influence of the chemical stimulation of medullary raphe nuclei by the stable TRH (thyrotropin-relsasing hormone) analog, RX 77368, on gastric contractility. Urethane-anesthetizcd rats were acutely implanted with miniature strain gauge force transducers on the corpus of the stomach for continuous recording of gastric contractility. Traces were analyzed by computer. Microinjections of vehicle or RX 77368 into the raphe pallidus or raphe obscurus were performed using pressure injection of 50 nl through glass micropipettes 30 min following basal recording of gastric contractility. RX 77368 (0.7–77 pmol) dose dependently stimulated gastric contractility when microinjected into the raphe pallidus and raphe obscurus. The stimulation of gastric contractions induced by microinjection of RX 77368 (77 pmol) into these raphc nuclei was completely blocked by vagotomy and prevented (raphe obscurus) or reduced (raphe pallidus) by atropine. RX 77368 (7.7–77 pmol) microinjected into the inferior olive, pyramidal tract, medial lemiscus was ineffective. These results demonstrate that chemical stimulation of the raphe pallidus and obscurus by RX 77368 stimulates gastric contractility through vagal and muscarinic pathways. These data suggest a role for medullary raphe nuclei in the central vagal regulation of gastric contractility.

Responses of phrenic motoneurones of the cat to stimulation of medullary raphe nuclei.

Responses of phrenic motoneurones to stimulation of the three medullary raphe nuclei (raphe magnus (r. magnus), raphe obscurus (r. obscurus) and raphe pallidus (r. pallidus] were recorded in anaesthetized and decerebrated cats. Stimulation of r. magnus or r. obscurus depressed phrenic motoneurones. Stimulation at 100 Hz reduced action potential frequency within each inspiratory burst, without appreciable changes in inspiratory duration, or number of inspiratory bursts per unit time. The depression was proportional to the stimulus intensity (40-160 microA) and frequency (12-100 Hz) and lasted throughout the period of stimulation. Intracellular recording revealed concomitant depression of central respiratory drive potentials (c.r.d.p.s) and increased membrane input resistance during r. obscurus or r. magnus stimulation. In motoneurones which discharged action potentials during expiratory as well as inspiratory phases following intracellular chloride injection, stimulation of r. magnus or r. obscurus depressed cell firing during both phases. Both c.r.d.p.s and reversed inhibitory post-synaptic potentials (i.p.s.p.s) were depressed. These findings indicate that the depression is not related to post-synaptic inhibition of phrenic motoneurones. Stimulation (100 Hz) of r. pallidus produced discharges of action potentials in phrenic motoneurones. Stimulation lengthened the duration of each inspiratory discharge in proportion to stimulus intensity. Continuous firing occurred throughout the period of stimulation with maximal intensities. Intracellular recordings revealed sustained depolarization and reduction in membrane input resistance during the discharge. Responses were recorded extracellularly from medullary inspiratory neurones of the dorsal respiratory group (d.r.g.) and ventral respiratory group (v.r.g.) and from vagal axons which fired in phase with phrenic nerve activity. Responses to raphe stimulation were similar to those recorded from phrenic motoneurones. Evidence is presented that the responses are not related to stimulation of decussating bulbo-spinal axons from d.r.g. or v.r.g. neurones. It is suggested that medullary respiratory neurones receive inhibitory and excitatory synaptic inputs from medullary raphe neurones. Hypercapnia (5% CO2 in O2) or hypoxia (15% O2 in N2) reduced markedly the inhibition produced during stimulation of r. obscurus or r. magnus, and restored expiratory-linked silent periods during stimulation of r. pallidus. Activation of Hering-Breuer or baroreceptor reflexes did not alter responses to r. pallidus stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Serotoninergic and non‐serotoninergic responses of phrenic motoneurones to raphe stimulation in the cat.

Experiments were conducted on anaesthetized, paralysed and artificially ventilated cats in order to determine if the altered discharge pattern of phrenic motoneurones recorded during stimulation of medullary raphe nuclei (raphe magnus (r. magnus), raphe obscurus (r. obscurus), raphe pallidus (r. pallidus] are related to release of serotonin (5-hydroxytryptamine, 5-HT) at synapses on respiratory neurones. Effects of 5-HT released by the neurotoxin p-chloroamphetamine (PCA) on spontaneous activity of phrenic motoneurones were also examined. In addition, responses of phrenic motoneurones to 5-HT applied by micro-electrophoresis were recorded. Stimulation (100 Hz) of r. magnus or r. obscurus depressed the spontaneous inspiratory discharges of phrenic motoneurones. Administration of the 5-HT receptor antagonists cinanserin, methysergide or methergoline reduced, but did not abolish, the inhibition. Inhibition of the neuronal reuptake of 5-HT with fluoxetine enhanced the inhibition and reduced the peak inspiratory action potential frequency of spontaneous discharges. Stimulation (100 Hz) of r. pallidus produced increased firing of phrenic motoneurones. Firing of phrenic motoneurones was evoked even during the normally quiescent expiratory phase of spontaneous respiratory activity. Antagonists at 5-HT receptors reduced the degree of tonic firing, resulting in partial restoration of expiratory pauses during r. pallidus stimulation. Inhibition of 5-HT reuptake, on the other hand, resulted in increased tonic firing. Release of 5-HT by PCA produced a rapid and severe reduction of phrenic nerve activity. Activity was restored by 5-HT receptor antagonists. In reserpine-treated cats, effects of stimulating medullary raphe nuclei were still pronounced, however 5-HT receptor antagonists had no effect on the responses. These results, along with the observation that 5-HT receptor antagonists are only partially effective in non-reserpinized cats, indicate that non-serotoninergic influences contribute as well to the responses evoked by raphe stimulation. Micro-electrophoretic application of 5-HT by large ejecting currents (100-200 nA) had weak stimulatory effects on twenty of forty-five phrenic motoneurones, which exhibited small increases in peak inspiratory discharge frequency during 5-HT application. Ejecting currents less than 100 nA were without effect. It is concluded that 5-HT analogues and agents which release endogenous 5-HT after parenteral administration do not act directly at synapses on the soma membranes of phrenic motoneurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Evidence for a serotonergically mediated sympathoexcitatory response to stimulation of medullary raphe nuclei

The cardiovascular role of serotonin (5-HT) containing neurons in the midline medullary raphe nuclei was studied in anesthetized cats. High frequency electrical stimulation of nucleus (n.) raphe (r.) pallidus, n.r. obscurus and n.r. magnus produced both pressor and depressor responses. Single shock stimulation of pressor sites produced an excitatory evoked potential of sympathetic nervous discharge (SND) recorded from the inferior cardiac nerve. Conversely, single shock stimulation of vasodepressor sites resulted in a computer-summed inhibition of SND. The mean conduction velocity in the sympathoexcitatory medullo-spinal pathway to sympathetic preganglionic neurons was calculated to be 1.24 m/s. The 5-HT antagonists methysergide and metergoline blocked the excitation of sympathetic activity evoked from medullary raphe nuclei. In contrast, these agents failed to alter the sympathoexcitatory response to electrical stimulation of lateral medulla pressor sites or the sympathoinhibitory response elicited by raphe stimulation. The 5-HT uptake inhibitor chlorimipramine increased the duration of the sympathoexcitatory response evoked from the raphe but not from the lateral medulla. Finally, mid-collicular transection did not effect the excitation of sympathetic activity elicited by stimulation of medullary raphe nuclei. These data suggest that serotonergic neurons in the midline medullary raphe nuclei provide an excitatory input to sympathetic neurons in the spinal cord.

Antagonism of stimulation-produced antinociception by intrathecal administration of methysergide or phentolamine

This study examined whether the antinociception produced by electrical stimulation of medullary raphe nuclei is mediated by activation of monoaminergic neurons projecting to the spinal cord. Ninety-four sites distributed about the midline of the medulla were stimulated and their ability to produce antinociception was determined using two different analgesiometric tests. Stimulation of sites in the nuclei raphe pallidus and raphe obscurus did not produce antinociception, but rather, produced tremor and, on occasion, extensor rigidity. In contrast, stimulation at sites located in the nucleus raphe magnus and the adjacent nucleus reticularis paragigantocellularis produced antinociception, as indicated by increased tail flick latencies and decreased responsiveness to noxious pinch applied to the extremities. Intrathecal administration of saline prior to electrical stimulation of these sites did not attenuate either the elevation of tail flick latencies or the decreased responsiveness to pinch. However, intrathecal administration of 30 μg of either methysergide or phentolamine prior to stimulation at these same sites significantly attenuated the increase in tail flick latency and restored responsiveness to pinch. Naloxone (1 mg/kg, s.c.) did not attenuate the stimulation-produced antinociception evoked from any of these sites. These data support the postulate that the antinociceptive effect of electrical stimulation of the nucleus raphe magnus and the nucleus reticularis paragigantocellularis is mediated by activation of serotonergic and noradrenergic neurons projecting to the spinal cord. The inability of either methysergide or phentolamine alone to completely antagonize the elevation of tail flick latency further suggests that the serotonergic and noradrenergic bulbospinal systems are coactivated by electrical stimulation of these sites.