Nucleus Raphe Magnus Of Rats Research Articles

Distributive characteristics of projection from vestibular nuclei to nucleus raphe magnus in rats**

BACKGROUNDMorphological studies have confirmed that vestibular nuclei accepts serotoninergic projections from nucleus raphe magnus, nucleus raphes pallidus, etc. But it is still unclear whether there is bi-directional association between vestibular nuclei and nucleus raphe magnus. OBJECTIVETo observe the characteristics of projective fibers from vestibular nuclei to nucleus raphe magnus using tetramethyl rhodamine (TMR) in rats, so as to provide more sufficient morphological evidence of neural association from vestibular nuclei. DESIGNAn observational experiment. SETTINGDepartment of Anatomy (K.K. Leung Brain Research Center), the Fourth Military Medical University of Chinese PLA. MATERIALSEighteen male SD rats of clean degree, weighing 250–280 g, were provided by the Experimental Animal Center of the Fourth Military Medical University of Chinese PLA. METHODSThe experiments were carried out in the laboratory of Department of Anatomy (K.K. Leung Brain Research Center), the Fourth Military Medical University of Chinese PLA from September 2006 to January 2007. All the rats were anesthetized with intraperitoneal injection of pentobarbital sodium, then according to the coordinates on the rat brain atlas, 0.1 µ L TMR (100 g/L) was injected into nucleus raphes magnus via the tip of glass microtubule by means of microinjection. Seven days later, the rats were anesthetized, then perfused and fixed to remove brain, and then frozen coronal brain sections were prepared. The retrogradely labeled neurons in the injected and projected sites were observed under fluorescence microscope. Light filters with evoked wave length of 540–553 nm and emission wave length ≥ 1 580 nm were selected to observe the orange TMR-labeled neurons. All the sections were observed and counted under the fluorescence microscope. MAIN OUTCOME MEASURESCharacteristics and number of retrogradely labeled neurons at different sites of nuclei. RESULTSTotally 18 SD rats were enrolled, 9 of them were excluded due to the deviation of injected site, and the other 9 were involved in the final analysis of results. The concentrated region of TMR injection was mainly restricted to nucleus raphes magnus, and diffused to the surrounding area to different extents. There were obvious differences in the distributions of the labeled neurons among the subdivisions in vestibular nuclei, as well as the distributions of the labeled neurons at different sites in the same subdivision. The majority of the labeled neurons distributed in the rostral levels of medial vestibular nucleus and the lateral vestibular nucleus, while fewer labeled neurons were observed in superior vestibular nucleus. CONCLUSION(1) There might be bi-directional association between vestibular nucli and nucleus raphe magnus, suggesting that nucleus raphe magnus played a role in the transmission and processing of vestibular information. (2) The projection from nucleus raphe magnus to vestibular nucleus has certain distributive characteristics in the region.

Modulatory effects of repeated psychophysical stress on masseter muscle nociception in the nucleus raphe magnus of rats.

Psychophysical stress can cause neural changes that increase nociception in the orofacial region, particularly the masseter muscle (MM). The nucleus raphe magnus (NRM), which is located in the brain stem, serves the crucial role of regulating nociception through descending modulatory pain control. However, it remains unclear if neural activities in the NRM are affected under psychophysical stress conditions. This study conducted experiments to assess (1) whether neural activity, indicated by Fos expression in an NRM that has experienced MM injury, is affected by the stress of repeated forced swim tests (FST); and (2) whether the selective serotonin reuptake inhibitor fluoxetine administered daily after an FST could affect the number of Fos-positive neurons in the NRM. Results revealed that the stress from repeated FSTs significantly increased the number of Fos-positive neurons in an NRM that had been affected by MM injury. Fluoxetine inhibited increases in the number of Fos-positive neurons in the NRM that occurred as a result of FSTs, but this was not observed in sham rats. These findings indicate that the stress from FSTs could increase nociceptive neural activity in an NRM that has experienced MM injury. This could be due, in part, to changes in serotonergic mechanisms.

Effects of Restraint Water-Immersion Stress-Induced Gastric Mucosal Damage on Astrocytes and Neurons in the Nucleus Raphe Magnus of Rats via the ERK1/2 Signaling Pathway

Restraint water-immersion stress (RWIS) consists of psychological and physical stimulation, and it has been utilized in the research of gastric mucosal damage. It has been shown by previous studies that the nucleus raphe magnus (NRM) is closely involved in the gastrointestinal function, but its functions on the stress-induced gastric mucosal injury (SGMI) have not been thoroughly elucidated to date. Consequently, in this research, we aim to measure the expression of astrocytic glial fibrillary acidic protein (GFAP), neuronal c-Fos, and phosphorylation extracellular signal regulated kinase 1/2 (p-ERK1/2) in the process of RWIS with immunohistochemistry and western blot methods. What is more, we detect the relation between astrocytes and neurons throughout the stress procedure and explore the regulation of the ERK1/2 signaling pathway on the activity of astrocytes and neurons after RWIS. The results indicated that all three proteins expression multiplied following peaked 3h substantially. The SMGI, astrocyte and neuron activity were affected after the astrocytotoxin L-A-aminohexanedioic acid (L-AA) and c-fos antisense oligonucleotide (ASO) injections. After the injection of PD98059, the gastric mucosal injury, astrocyte and neuron activity significantly fell off. These results suggested that RWIS-induced activity of astrocytes and neurons in the NRM may play a significant part in gastric mucosa damage via the ERK1/2 signaling pathway.

Oxytocin in rat nucleus raphe magnus influences pain modulation

The main function of Nucleus raphe magnus (NRM) is mostly pain mediation. Our previous study has demonstrated that oxytocin (OXT) regulates antinociception through the central nervous system rather than the peripheral organs, and pain stimulation increases OXT concentration in the NRM. The experiment was designed to investigate OXT in the rat NRM effect on pain modulation. The results showed that 1) pain stimulation increased OXT concentration in NRM perfusion liquid; 2) Intra-NRM microinjection of OXT increased the pain threshold in a dose-dependent manner, whereas intra-NRM microinjection of OXT receptor antagonist, desGly-NH2, d(CH2)5[D-Tyr2, Thr-sup-4]OVT decreased the pain threshold; 3) NRM pre-treatment with OXT receptor antagonist completely attenuated the pain threshold increase induced by intra-NRM administration of OXT. The data suggested that OXT in NRM was involved in antinociception via OXT receptors.

Arginine vasopressin in hypothalamic paraventricular nucleus is transferred to the nucleus raphe magnus to participate in pain modulation

Hypothalamic paraventricular nucleus (PVN) is one of the main sources of arginine vasopressin (AVP) synthesis and secretion. AVP is the most important bioactive substance in PVN regulating pain process. Our pervious study has pointed that pain stimulation induced AVP increase in the nucleus raphe magnus (NRM), which plays a role in pain modulation. The present study was designed to investigate the source of AVP in the rat NRM during pain process using the methods of nucleus push–pull perfusion and radioimmunoassay. The results showed that pain stimulation increased the AVP concentration in the NRM perfusion liquid, PVN cauterization inhibited the role that pain stimulation induced the increase of AVP concentration in the NRM perfusion liquid, and PVN microinjection of l-glutamate sodium, which excited the PVN neurons, could increase the AVP concentration in the NRM perfusion liquid. The data suggested that AVP in the PVN might be transferred to the NRM to participate in pain modulation.

Arginine vasopressin antinociception in the rat nucleus raphe magnus is involved in the endogenous opiate peptide and serotonin system

Arginine vasopressin (AVP) in the nucleus raphe magnus (NRM) has been implicated in antinociception. This communication was designed to investigate which neuropeptide and neurotransmitter are involved in AVP antinociception in the rat NRM. The results showed that (1) in the NRM perfuse liquid, pain stimulation could increase the concentrations of AVP, leucine-enkephalin (L-Ek), methionine-enkephalin (M-Ek), β-endorphin (β-Ep), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), but not change the concentrations of dynorphinA 1–13 (DynA 1–13), oxytocin, achetylcholine, choline, γ-aminobutyric acid, glutamate, dopamine, 3,4-dihydroxyphenylacetic acid, homovanilic acid, norepinephrine and epinephrine; (2) in the NRM perfuse liquid, AVP increased the concentrations of L-Ek, M-Ek, β-Ep, DynA 1–13, 5-HT and 5-HIAA, but did not change the concentrations of oxytocin and the other studied neurotransmitters; (3) AVP antinociception in the NRM was attenuated by cypoheptadine (a 5-HT-receptor antagonist) or naloxone (an opiate receptor antagonist), but was not influenced by the other studied receptor antagonists. The data suggested that AVP antinociception in the NRM might be involved in endogenous opiate peptide and 5-HT system.

Antinociceptive role of oxytocin in the nucleus raphe magnus of rats, an involvement of μ-opioid receptor

Recent studies showed that oxytocin plays an important role in nociceptive modulation in the central nervous system. The present study was undertaken to investigate the role of oxytocin in antinociception in the nucleus raphe magnus (NRM) of rats and the possible interaction between oxytocin and the opioid systems. Intra-NRM injection of oxytocin induced dose-dependent increases in hindpaw withdrawal latencies (HWLs) to noxious thermal and mechanical stimulation in rats. The antinociceptive effect of oxytocin was significantly attenuated by subsequent intra-NRM injection of the oxytocin antagonist 1-deamino-2- d-Tyr-(Oet)-4-Thr-8-Orn-oxytocin. Intra-NRM injection of naloxone dose-dependently antagonized the increased HWLs induced by preceding intra-NRM injection of oxytocin, indicating an involvement of opioid receptors in oxytocin-induced antinociception in the NRM of rats. Furthermore, the antinociceptive effect of oxytocin was dose-dependently attenuated by subsequent intra-NRM injection of the μ-opioid antagonist β-funaltrexamine (β-FNA), but not by the κ-opioid antagonist nor-binaltorphimine (nor-BNI) or the δ-opioid antagonist naltrindole. The results demonstrated that oxytocin plays an antinociceptive role in the NRM of rats through activating the oxytocin receptor. Moreover, μ-opioid receptors, not κ and δ receptors, are involved in the oxytocin-induced antinociception in the NRM of rats.

The nucleus raphe magnus modulates hypoxia-induced hyperventilation but not anapyrexia in rats

The nucleus raphe magnus (NRM) is one of the brainstem cell groups involved in physiological responses to hypoxia. Thus, we tested the hypothesis that the NRM modulates hypoxia-induced hyperventilation and anapyrexia. To this end, we assessed the participation of NRM in the respiratory and thermoregulatory responses to hypoxia using ibotenic acid lesions produced in the NRM of rats. Our results demonstrated that, under resting breathing, NRM plays no role in ventilation or body temperature. Hypoxia caused hyperventilation and anapyrexia in all groups. NMR lesions elicited an increased ventilatory response to hypoxia due to a higher tidal volume ( V T) but did not affect hypoxia-induced anapyrexia . Therefore, we conclude that NRM exerts an inhibitory modulation of breathing during hypoxia, acting on V T, but plays no role in the hypoxia-induced anapyrexia.

Kappa-Opioid receptor-mediated enhancement of the hyperpolarization-activated current (Ih) through mobilization of intracellular calcium in rat nucleus raphe magnus

kappa-Opioid receptor-mediated enhancement of the hyperpolarization-activated current (Ih) through mobilization of intracellular calcium in rat nucleus raphe magnus

Kappa-opioid receptor-mediated enhancement of the hyperpolarization-activated current (I(h)) through mobilization of intracellular calcium in rat nucleus raphe magnus.

The hyperpolarization-activated current (Ih) is important in the control of resting membrane potential, in the regulation of network firing pattern and in the modulation of presynaptic transmitter release in central neurons. Recent studies on native and cloned Ih channels have demonstrated that the Ih channel is commonly modulated by cAMP through a positive shift in its voltage dependence without a change in its maximum current. The present study demonstrates that activation of kappa-opioid receptors enhances Ih by increasing its maximum current in brainstem neurons in the nucleus raphe magnus. Agents that interfere with the release of intracellular calcium from calcium stores altered the maximum Ih and significantly attenuated the kappa-receptor-mediated enhancement of Ih. These results suggest that kappa-opioid receptors enhance the maximum Ih by mobilizing intracellular calcium from calcium stores. This provides a physiological function for kappa-receptor-stimulated calcium release and may suggest another Ih-regulating mechanism by intracellular calcium in central neurons.

Expression of 5-HT 1A receptor mRNA in rat nucleus raphe magnus neurons after peripheral inflammation

The present study demonstrated that 5-HT 1A receptor mRNA was expressed with moderate level in the NRM neurons. Most of 5-HT 1A receptor mRNA positive cells were 5-HT neurons, suggesting the majority of 5-HT 1A receptor in the NRM might be autoreceptors. Eight hours after carrageenan inflammation, the expression of 5-HT 1A receptor mRNA in the NRM neurons, especially in the 5-HT neurons, was significantly increased. These results suggest that synthesis of 5-HT 1A receptors, including 5-HT 1A autoreceptors, is increased in the NRM during peripheral inflammation.

Involvement of neuropeptide Y and Y1 receptor in antinociception in nucleus raphe magnus of rats

The nociceptive response latencies increased significantly after intra-nucleus raphe magnus administration of 0.1 or 0.4 nmol of neuropeptide Y, but not 0.04 nmol, in rats. The neuropeptide Y-induced increases in hindpaw withdrawal latency were reversed by following injection of 0.42 nmol of the Y1 antagonist, NPY(28–36). The results indicate that NPY plays an antinociceptive role in nucleus raphe magnus in rats, which is mediated by the Y1 receptor. Furthermore, the neuropeptide Y-induced increases in hindpaw withdrawal latency were attenuated by following intra-nucleus raphe magnus injection of 6 nmol of the opioid antagonist naloxone, indicating that there is an interaction between NPY and opioids in nucleus raphe magnus.

Anti-nociceptive effects of calcitonin gene-related peptide in nucleus raphe magnus of rats: an effect attenuated by naloxone

The present study investigated the role of calcitonin gene-related peptide (CGRP) on nociception in nucleus raphe magnus (NRM) and the interaction between CGRP and opioid peptides in NRM of rats. CGRP-like immunoreactivity was found at a concentration of 6.0±0.77 pmol/g in NRM tissue of ten samples of rats, suggesting that it may contribute to physiological responses orchestrated by the NRM. The hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation increased significantly after intra-NRM administration of 0.5 or 1 nmol of CGRP in rats, but not 0.25 nmol. The anti-nociceptive effect induced by CGRP was antagonized by following intra-NRM injection of 1 nmol of the CGRP receptor antagonist CGRP8-37. Furthermore, the CGRP-induced anti-nociceptive effect was attenuated by following intra-NRM administration of 6 nmol of naloxone. The results indicate that CGRP and its receptors play an important role in anti-nociception, and there is a possible interaction between CGRP and opioid peptides in NRM of rats.

Correlations between serotonin level and single-cell firing in the rat's nucleus raphe magnus

The relation between serotonin release and electrical activity was examined in the nucleus raphe magnus of rats anesthetized with pentobarbital. Serotonin levels were monitored through a carbon-fiber microelectrode by fast cyclic voltammetry (usually at 1 Hz). Single-cell firing was recorded through the same microelectrode, except during the voltammetry waveform and associated electrical artifact (totaling about 30 ms). Multi-barrel micropipettes incorporating the voltammetry electrode were used for iontophoresis of drugs. Cells were inhibited, excited or unaffected by noxious mechanical skin stimulation. These were respectively designated as off(M) cells, on(M) cells and neutral(M) cells, M denoting mechanical. During 3 min of pinching, serotonin slowly rose near seven of 14 on(M) cells and 26 of 46 off(M) cells; it fell near two off(M) cells; it was unchanged near all other cells, including six neutral(M) cells. On a finer spatiotemporal scale, near four of seven on(M) cells, 10 of 14 off(M) cells and 0 of four neutral(M) cells, average serotonin levels fell significantly within ±100 ms of spontaneous spikes. Lower serotonin may have caused the higher spike probability; the converse is theoretically unlikely, since delays between release and detection are estimated to exceed 100 ms. Increased serotonin and decreased firing were always seen following iontophoresis or intravenous injection (1 mg/kg) of the serotonin re-uptake inhibitor clomipramine ( n=7). Iontophoresis of ±propranolol, whose serotonergic actions include antagonism and partial agonism at 5-HT1 receptors, also increased serotonin and decreased firing ( n=4). Methiothepin (intravenous, 1 mg/kg), whose serotonergic actions include 5-HT1 and 5-HT2 antagonism, typically raised serotonin levels (four of five cells) and always blocked inhibition by clomipramine ( n=3). Iontophoresis of glutamate always lowered serotonin and increased firing ( n=4). Since serotonin levels and firing were usually inversely correlated, except near on(M) cells during pinch, we propose that serotonin is released from terminals of incoming nociceptive afferents. Prior neuroanatomical knowledge favors a midbrain origin for these afferents, while some of the drug findings suggest that their terminals possess inhibitory serotonergic autoreceptors, possibly of 5-HT1b subtype. The released serotonin could contribute to the inhibition of off(M) cells and excitation of on(M) cells by noxious stimulation, since inhibitory 5-HT1a receptors and excitatory 5-HT2 receptors, respectively, have previously been shown to dominate their serotonergic responses.

The effect of alpha2-adrenergic drugs on the activity of neurons in the rat nucleus raphe magnus in vitro.

The nucleus raphe magnus (NRM) is an important descending inhibitory system for pain transmission. We tested whether clonidine, an alpha2-adrenergic agonist, and yohimbine, an alpha2-adrenergic antagonist, modulate the activity of NRM neurons using extracellular recording in a rat brainstem slice preparation. Clonidine 1-20 microM increased firing frequencies (FF) in 22 (37%) and decreased FF in 6 (10%) spontaneously active neurons. Correlation between the concentrations of clonidine and FF changes was unremarkable. Eight spontaneously active neurons (13%) showed increases followed by decreases in FF with increasing doses of clonidine. The remaining 24 neurons (40%) showed no change in FF. Yohimbine 1 microM decreased FF in 38 spontaneously active neurons (58%), whereas the remaining 27 neurons (42%) showed no change in FF. In some neurons, yohimbine antagonized the increase or decrease in FF by application of clonidine. In three silent neurons (25%), clonidine (5 or 10 microM) induced firing activity, which stopped or decreased with the increasing doses of clonidine. In the remaining nine neurons (75%), clonidine did not induce firing activity. We conclude that activation and inhibition of alpha2-adrenergic receptors of NRM neurons augments and suppresses output of the descending inhibitory pain pathway. The nucleus raphe magnus is implicated in descending control of the nociceptive processes. We found that clonidine and yohimbine increased and decreased, respectively, the firing activity of a substantial number of nucleus raphe magnus neurons. Clonidine and may facilitate and yohimbine may reduce the outflow of the descending inhibitory pathway.

Role of the Nucleus Raphe Magnus in Antinociception Produced by ABT-594: Immediate Early Gene Responses Possibly Linked to Neuronal Nicotinic Acetylcholine Receptors on Serotonergic Neurons

Recently, a novel cholinergic channel modulator, (R)-5-(2-azetidinylmethoxy)-2-chloropyridine (ABT-594), was shown to produce potent analgesia in a variety of rodent pain models when administered either systemically or centrally into the nucleus raphe magnus (NRM). The purpose of the present study was to investigate the possible supraspinal contribution of ABT-594 by assessing its ability to induce expression of the immediate early gene c-fos, a biochemical marker of neuronal activation, in the NRM of rats. Putative serotonergic neurons in the NRM, a medullary nucleus proposed to be involved in descending antinociceptive pathways, were identified immunohistochemically using a monoclonal antibody (mAb) against tryptophan hydroxylase. ABT-594 (0.03-0.3 micromol/kg, i.p.) produced a dose-dependent induction of Fos protein that was blocked by the central nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (5 micromol/kg, i.p.) but not by the peripheral nAChR antagonist hexamethonium (15 micromol/kg, i.p.). Immunohistological studies using mAb 299 revealed the expression of alpha4-containing nAChRs in the NRM. The alpha4 immunostaining was dramatically reduced by pretreating (30 d) animals with the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), which was previously shown to substantially attenuate the antinociceptive actions of ABT-594. In a double immunohistochemical labeling experiment, coexpression of the serotonin marker tryptophan hxdroxylase and the alpha4 nAChR subunit in NRM neurons was observed. These results suggest that the analgesic mechanism of ABT-594 may in part involve the activation of the NRM, a site where alpha4-containing nAChRs are expressed by serotonergic neurons.

Supraspinal Influence on Hindlimb Withdrawal Thresholds and Mustard Oil-Induced Secondary Allodynia in Rats

We examined the role of supraspinal structures in secondary allodynia induced by mustard oil in awake rats. To produce allodynia (=unpleasent sensation evoked by innocuous stimuli), mustard oil (50%) was applied for 2 min to the skin of the ankle of one hindlimb. Mechanical hypersensitivity of the skin was tested by determining the hindlimb withdrawal threshold to a series of monofilaments applied to the glabrous foot pad (=distal to the mustard oil-treated ankle). In intact rats, mustard oil produced a secondary allodynia in the mustard oil-treated hindlimb as indicated by a decreased withdrawal threshold to mechanical test stimuli applied to the glabrous skin (=outside the mustard oil-treated ankle), whereas the withdrawal threshold in the contralateral (=control) hindlimb was not changed. Following spinalization, mustard oil treatment produced no secondary allodynia, but the interpretation of this finding was complicated by a concomitant bilateral elevation of hindlimb withdrawal thresholds to mechanical skin stimulation. However, the spinalized rats had shorter tail-flick latencies to radiant heat than intact rats. Administration of an opioid antagonist, naloxone (1 mg/kg, SC), had no effect on withdrawal thresholds in spinalized animals. Importantly, microinjection of lidocaine (4%) into the nucleus raphe magnus in rats with an intact spinal cord had a selective antiallodynic effect when the injection volume was 1.0 μl but not when it was 0.5 μl. Lidocaine (4%, 0.5 μl) in the lateral reticular nucleus of the medulla also attenuated the spinal hypersensitivity, however, concomitantly with motor side effects, due to which this finding maybe artificial. It is concluded that brain stem spinal pathways, originating adjacent to but not within the raphe magnus, contribute to the behavioral expression of secondary allodynia induced by neurogenic inflammation of the skin. Furthermore, there is a differential tonic control of various spinal reflexes by the brain stem as indicated by the dissociative effects of spinalization on mechanically induced hindlimb withdrawal vs. heat-induced tail-flick reflex.

Muscarine hyperpolarizes a subpopulation of neurons by activating an M2 muscarinic receptor in rat nucleus raphe magnus in vitro

It has been shown previously that the muscarinic cholinergic system in the nucleus raphe magnus (NRM) is involved in the modulation of nociception. In this study, we examined the direct actions of muscarine on the NRM neurons in a slice preparation. Muscarine (1-30 microM) produced a dose-dependent hyperpolarization in a subpopulation of the NRM cells that contain 5-hydroxytryptamine (5-HT). In voltage clamp, the muscarine-induced outward current reversed polarity at the potassium equilibrium potential and was characterized by strong inward rectification. The reversal potential was dependent on external potassium concentration, suggesting that the hyperpolarization induced by muscarine was mediated through an increase in an inwardly rectifying potassium conductance. 5-HT also hyperpolarized these cells by increasing the same inwardly rectifying potassium conductance. The concentration-response curve for muscarine (EC50 = 2.7 microM) was shifted in a parallel manner to the right by increasing concentrations of pirenzepine (300 nM to 3 microM) and methoctramine (50-200 nM). Schild analysis revealed that the equilibrium dissociation constant (Kd) was 230 nM for pirenzepine and was estimated to be less than 30 nM for methoctramine. These results indicate that the muscarinic receptor mediating the muscarine activation of the potassium conductance in these cells is of the M2 subtype. The present results suggest an inhibitory cholinergic postsynaptic modulation on the activity of a subpopulation of serotonergic neurons that are involved in antinociceptive function in the NRM.

Modulation by serotonin of the neurons in rat nucleus raphe magnus in vitro

Nucleus raphe magnus contains a large population of raphe-spinal serotonergic neurons that are thought to be involved in descending control of pain transmission and the modulation of opioid analgesia. Intracellular recordings were made from nucleus raphe magnus neurons in the slice preparation. Cells were divided into two groups, primary and secondary cells, based on the action potential waveform and response to opioids, as reported previously. In some experiments, cells were filled with biocytin and 5-hydroxytryptamine-containing cells were identified immunohistochemically. Of the primary cells that were filled with biocytin, 93% stained for 5-hydroxytryptamine; 90% of biocytin-filled secondary cells were unlabeled for 5-hydroxytryptamine. Previous studies have shown that primary cells are disinhibited by opioids; the finding that most primary cells are serotonergic suggests that at least some 5-hydroxytryptamine-containing neurons in the nucleus raphe magnus are excited by opioid analgesics. 5-Hydroxytryptamine hyperpolarized cells in both primary and secondary cell groups. The 5-hydroxytryptamine agonists (±)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide and 5-carboxamidotryptamine mimicked this action of 5-hydroxytryptamine, indicating that the 5-hydroxytryptamine 1A-subtype mediated this hyperpolarization. The hyperpolarization was mediated by an increase in potassium conductance that rectified inwardly. Local electrical stimulation of afferents evoked an inhibitory postsynaptic potential in primary cells. The inhibitory postsynaptic potential reversed polarity at the potassium equilibrium potential and was blocked by 5-hydroxytryptamine 1A receptor antagonists. It is proposed that the 5-hydroxytryptamine 1A receptor on serotonergic primary cells may function as an autoreceptor to regulate the activity. The role of the 5-hydroxytryptamine 1A receptor on non-serotonergic secondary cells is unclear.

Modulation of cortical evoked potentials by stimulation of nucleus raphe magnus in rats.

1. In pentobarbital sodium-anesthetized rats, we evaluated changes in cortical evoked potentials (EPs) associated with electrical and chemical stimulation of nucleus raphe magnus (NRM). A condition-test (C-T) paradigm was used. Cortical EPs were produced by test stimuli delivered to a hindpaw or the thalamic ventral posterior lateral nucleus (VPL; electrical stimulation), or by photic stimulation of the eyes or electrical stimulation of contralateral homotopical cortex (transcallosal EPs). These test stimuli were then preceded by electrical or chemical conditioning stimulation (CS) delivered to NRM through a stereotaxically implanted electrode or injection cannula, respectively. Effects of CS on EPs produced by the test stimuli were characterized. 2. Electrical CS preceding a test stimulus delivered to the foot reduced the amplitude of EPs at thresholds as low as 10-25 microA. The magnitude of EP reduction was dependent on CS intensity, frequency, and the C-T interval. Optimal parameters were trains of 10 pulses (400 Hz) delivered at a C-T interval of 5-10 ms. Injection of glutamate and lidocaine into NRM demonstrated that these effects were due to activation of NRM neurons and not to current spread to medial lemniscus (ML). NRM CS also reduced cortical EPs produced by test stimulation in VPL but did not alter EPs from visual stimulation or from electrical stimulation of contralateral homotopical cortex. 3. These findings suggest that NRM CS attenuates EPs by inhibiting thalamic or thalamocortical afferent activity. Because NRM CS affected all components of the cortical EPs, the effect appears to involve alteration of general sensory activity and is not nociception specific.(ABSTRACT TRUNCATED AT 250 WORDS)