Neurons In Dorsal Raphe Nucleus Research Articles

Microdialysis perfusion of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH- DPAT) in the dorsal raphe nucleus decreases serotonin release and increases rapid eye movement sleep in the freely moving cat

In vivo microdialysis was used to analyze the role of dorsal raphe nucleus (DRN) neurons in regulating the sleep-waking cycle. Measurements of extracellular serotonin (5-HT) were made in the DRN of freely moving adult cats before and during microdialysis perfusion of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A receptor agonist, in artificial CSF. Behavioral state alterations were measured by simultaneous polygraphic recordings. During waking and artificial CSF perfusion of probes histologically localized to the DRN, extracellular 5-HT was 4 fmol/7.5 micro L dialysate sample. With the addition of 8-OH-DPAT (10 microM in artificial CSF) to the perfusate, 5-HT levels in the same state decreased 50%, to 2 fmol/sample (p < 0.01), presumably through 5-HT1A autoreceptor-mediated inhibition of serotonergic neural activity. Concomitantly, this 8-OH-DPAT perfusion produced a short latency, threefold increase in rapid eye movement (REM) sleep, from 10 to 30% of the total recorded time (p < 0.05), whereas waking was not significantly affected. In contrast, and suggesting DRN specificity, 8-OH-DPAT delivery through a probe in the aqueduct did not increase REM sleep but rather tended to increase waking and decrease slow wave sleep. The data on REM sleep provide the first biochemically validated and direct evidence that suppression of DRN serotonergic activity increases REM sleep, and furnish a key complement to our laboratory's in vitro data indicating that mesopontine cholinergic neurons, a target of DRN projections, are inhibited by 5-HT. The 8-OH-DPAT-induced reduction of DRN 5-HT is consistent with the hypothesis that the concomitant REM sleep disinhibition is mediated by DRN serotonergic projections to mesopontine cholinergic neurons, which other data implicate in REM sleep production.

Increase by the ORL1 receptor (opioid receptor‐like1) ligand, nociceptin, of inwardly rectifying K conductance in dorsal raphe nucleus neurones

The actions of the endogenous ORL1-receptor (opioid receptor-like1) ligand, nociceptin, on the membrane properties of rat dorsal raphe nucleus neurones were examined by use of whole-cell patch clamp recording in brain slices. Nociceptin produced an outward current in all neurones tested, with an EC50 of 12 +/- 2 nM. Dynorphin A (100 nM to 1 microM) produced little outward current. Outward currents reversed polarity near the predicted K+ equilibrium potential in both 2.5 mM (measured/predicted = -105 mV/-104 mV) and 6.5 mM (measured/predicted = -80 mV/-77 mV) extracellular K+. The conductance increase was larger between -120 and -130 mV than between -70 and -80 mV, conductance. The outward current produced by nociceptin was similar to, and occluded by, high concentrations of baclofen, demonstrating actions on the same population of K channels. Naloxone (1 microM) failed to inhibit outward currents produced by nociceptin. These results are consistent with the reported high density of ORL1 receptor mRNA in dorsal raphe nucleus and with inhibitory actions of nociceptin in cells expressing ORL1.

A 5-hydroxytryptamine lesion markedly reduces the incidence of burst-firing dorsal raphe neurones in the rat

Recently, we described neurones in the rat dorsal raphe nucleus (DRN) with electrophysiological characteristics typical of 5-hydoxytryptamine (5-HT) neurones except that the neurones fired brief burst. Here we report the effect of 5-HT lesions on the incidence of these burst-firing neurones. In vivo extracellular recordings revealed that in rats pretreated with the selective 5-HT neurotoxin, 5,7-dihydroxytryptamine, the occurrence of typical 5-HT neurones was significantly decreased (80%) compared to controls. In these 5-HT lesioned animals, the number of the burst-firing DRN neurones was also significantly reduced (91%). Neurones previously characterised as not containing 5-HT, were not altered by the lesion. These data are further evidence to support our hypothesis that burst-firing neurones in the DRN contain 5-HT.

Effect of chemical stimulation of the dorsal raphe nucleus on cerebral blood flow in rat

We have previously shown that electrical stimulation of the dorsal raphe nucleus (DRN) can increase or decrease cerebral blood flow (CBF). We now sought to determine whether the CBF responses are mediated by DRN neurons or fibers of passage. In anesthetized rat, the DRN was stimulated chemically ( l-glutamate, kainate) and CBF in parietal cortex was measured by laser-Doppler flowmetry. Microinjection of kainate (5 nmol), but not l-glutamate, into DRN increased CBF (28 ± 22%; P < 0.05). Decreased CBF to DRN stimulation was not observed. We conclude that stimulation of DRN neurons increases CBF.

Inhibition of median and dorsal raphe neurones following administration of the selective serotonin reuptake inhibitor paroxetine

Acute systemic injection of selective serotonin reuptake inhibitors (SSRIs) decreases 5-HT neuronal firing in the dorsal raphe nucleus (DRN). Recent data, however, question whether these drugs also inhibit the firing of 5-HT neurones in the median raphe nucleus (MRN). Using in vivo extracellular electrophysiological recording techniques in the chloral hydrate anaesthetised rat, we have tested the effect of acute administration of the SSRI, paroxetine, on 5-HT neuronal activity in the MRN and DRN. Presumed 5-HT neurones in the MRN displayed the same electrophysiological characteristics as those in the DRN, the only detectable difference being that MRN neurones showed a significantly (p < 0.001) slower mean (+/- SEM(n)) spontaneous firing rate (MRN, 5.6 +/- 0.9 (14) spikes/10 s; DRN, 13.5 +/- 1.6 (24) spikes/10 s). Paroxetine caused a dose-related (0.1-0.8 mg/kg i.v.) inhibition of all MRN neurons tested (n = 8), producing a complete cessation of cell-firing at the highest doses. DRN neurones (n = 9) responded in a similar fashion. Furthermore, paroxetine inhibited MRN and DRN neurones with almost identical potency (MRN ED50 259 +/- 57 micrograms/kg i.v.: DRN ED50 243 +/- 49 micrograms/kg i.v.). In the majority of cells tested, the effect of paroxetine was reversed by the 5-HT1A receptor antagonists spiperone or (+)WAY100135, implicating the involvement of the 5-HT1A autoreceptor. The selective 5-HT1A receptor agonist 8-OH-DPAT also inhibited the firing of MRN (n = 5) and DRN (n = 12) neurones and with equal potency (MRN ED50, 1.32 +/- 0.40 microgram/kg i.v.: DRN ED50, 1.19 +/- 0.23 microgram/kg i.v.).(ABSTRACT TRUNCATED AT 250 WORDS)

Single-unit recordings at dorsal raphe nucleus in the awake-anesthetized rat: spontaneous activity and responses to cutaneous innocuous and noxious stimulations

In this study, we recorded the single-unit activity of the dorsal raphe nucleus (DRN) in rats tested first awake and, a few days later, anesthetized with sodium pentobarbital and recorded again. This was achieved by means of a small chronically implanted device supporting a 25 μm platinum-iridium wire as the recording electrode. In both the awake and anesthetized conditions, and in agreement with most of the studies performed at the DRN level, we found that a vast majority of the units, displaying small amplitude and long-duration action potentials, possessed a low level of spontaneous activity (0.2–4 Hz). Among these units, found in greater number under pentobarbital, it was possible to establish that this activity was regular or irregular, in accordance with the literature reports. However, as opposed to these studies, we determined that the ‘regularity’ was relative, only noticeable in more or less prolonged phases of activity. In particular, we never recorded the so-called ‘clock-like’ activity, largely reported as an unambiguous criterion for selecting the serotoninergic neurons. In both the awake and anesthetized conditions, the responses of the DRN neurons to peripheral mechanical innocuous and noxious stimulations were observed in only one-half of the units recorded and were weak in comparison to other results that we obtained at the nucleus raphe magnus level in previous studies. When present, these responses were excitation or inhibition, occurring during or after the stimulus application. These results question the direct involvement of the DRN in acute nociception.

Synaptic relations of neurotensinergic neurons in the dorsal raphe nucleus.

The ultrastructure and synaptic relations of neurotensinergic neurons in the rat dorsal raphe nucleus (DRN) were examined. The neurotensin-like immunoreactive (NT-L1) neurons in the DRN were fusiform or spherical. The NT-LI perikarya could only be detected in colchicine-treated animals whereas the immunoreactive axon terminals could only be found in the animals not treated with colchicine. Although many NT-LI dendrites received synapses from nonimmunoreactive axon terminals, the NT-LI perikarya received few synapses. NT-LI axon terminals also made synapses on nonimmunoreactive dendrites. Occasionally, synapses were found between the NT-LI axon terminals and NT-LI dendrites in the cases in which the animals were not treated with colchicine.

Immunohistochemical evidence that central serotonin neurons produce dopamine from exogenous l-DOPA in the rat, with reference to the involvement of aromatic l-amino acid decar☐ylase

The aim of the present study is to examine whether aromatic l-amino acid decar☐ylase (AADC) catalyzes the conversion of exogenous l-3,4-dihydroxyphenylalanine ( l-DOPA) to dopamine in serotonin neurons of the rat dorsal raphe nucleus. First, in order to confirm the localization of AADC in central serotonin neurons, we used an immunoperoxidase method for AADC and demonstrated that the distribution of AADC-containing neurons in the dorsal raphe nucleus corresponds very closely to the previous description on the distribution of serotonin-immunoreactive neurons. Second, in the rat that received intraperitoneally l-DOPA plus a peripheral AADC inhibitor, we used a double-labeling immunofluorescence method and showed that serotonin-stained neurons of the dorsal raphe nucleus were also immunoreactive to dopamine. The present result suggests that AADC decar☐ylating l-5-hydroxytryptophan to serotonin in physiological conditions is also able to catalyze the in vivo decar☐ylation of exogenous l-DOPA.

Blockade of transmission at NMDA receptors facilitates the electrical and synthetic activity of ascending serotoninergic neurones

This study examined the influence of N- methyl- d- aspartate (NMDA) receptors upon the activity of serotoninergic neurones projecting from the rat dorsal raphe nucleus (DRN) to the striatum of rats. The channel blocker ( + )-MK 801 (0.04–0.63 mg/kg, s.c.) augmented striatal accumulation of the serotonin (5-HT) precursor, 5-hydroxytryptophan (5-HTP), in rats treated with the inhibitor of decarboxylase, NSD 1015: the maximal effect of ( + )-MK 801 was 164% relative to vehicle values ( = 100%). In analogy, (+)-MK 801 (0.01–0.5 mg/kg, i.v.) increased the firing rate of DRN neurones with a maximal effect of 204%. This action was stereospecific in that (-)-MK 801, which shows lower affinity at NMDA receptors, enhanced firing only at higher doses. The selective, competitive antagonist at the NMDA recognition site, CPP (0.5–8.0 mg/kg, i.v.), also facilitated the firing rate of DRN neurones, though with a maximal effect (137%) less than of (+)-MK 801. Further, CPP (40.0 mg/kg, s.c.) did not significantly modify striatal 5-HT synthesis. While NMDA did not significantly modify DRN firing alone, it abolished the facilitatory action of CPP, consistent with a competitive interaction at the NMDA recognition site. In conclusion, blockade of NMDA receptors specifically facilitates the activity of ascending serotoninergic neurones.

The effect of clonidine on the activity of neurons in the rat dorsal raphe nucleus in vitro.

The dorsal raphe (DR) nucleus is a system of nuclei in the midline of the lower brainstem, which is considered one of the most important nuclei in the modulation of pain in the central nervous system. Central noradrenergic systems play an important role in the control of cardiovascular regulation and pain transmission. Clonidine, an alpha 2-adrenergic agonist is used extensively in anesthesia research. In this study, we evaluated the involvement of clonidine in the activity of DR nucleus and its possible role in pain modulation. Seventy-four neurons within the DR nucleus in the rat brainstem slice preparation were tested using extracellular recording techniques. Application of noradrenaline (NA), 50 mumol/L, induced firing activity in 68 neurons tested (92%). NA produced a regular long-lasting firing activity on the DR neurons. Fifty-six neurons (88%) previously excited by NA were inhibited by clonidine, 20 mumol/L. Clonidine suppressed the firing activity of neurons. The results indicate that the firing of DR neurons was under noradrenergic influence and was inhibited by clonidine, which in turn alters nociception by modifying the central serotonergic system.

Identification of periaqueductal gray and dorsal raphe nucleus neurons projecting to both the trigeminal sensory complex and forebrain structures: a fluorescent retrograde double-labeling study in the rat

The midbrain periaqueductal gray (PAG) including the dorsal raphe nucleus (DR) has been known to contain serotoninergic neurons projecting to many brain regions. Employing fluorescent retrograde double labeling combined with immunofluorescence histochemistry for serotonin (5-HT), we examined in the rat whether or not single PAG/DR neurons with 5-HT send their axons to both the trigeminal sensory complex and forebrain regions. Stereotaxic injections of Diamidino Yellow (DY) and Fast Blue (FB) were performed unilaterally; DY was injected into the caudal spinal trigeminal nucleus or principal sensory trigeminal nucleus, and FB into the ventrolateral orbital cortex, nucleus accumbens or amygdala. A small percentage of PAG/DR neurons were doubly labeled with DY and FB, and the majority of them showed 5-HT-like immunoreactivity (5-HT-LI). Most of these 5-HT-LI PAG/DR neurons that were indicated to send their axons simultaneously to both the trigeminal sensory complex and forebrain regions were distributed in the ventrolateral PAG subdivision and ventral aspects of the medial PAG subdivision at the middle and caudal PAG levels, bilaterally with a predominant distribution on the side ipsilateral to the injections. This indicates a possible role of these PAG/DR neurons in the limbic or affective-motivational aspect of the pain-related neural system.

Intraocular co-grafts of fetal dorsal raphe nucleus and suprachiasmatic nucleus

Serotonergic neurons in the fetal dorsal raphe nucleus were grafted together with fetal anterior hypothalamic tissue including the suprachiasmatic nucleus (SCN) to the anterior eye chamber of adult rats. After 6 weeks transplantation, the double grafts were immunocytochemically examined using antisera against serotonin, arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP). The raphe grafts contained a large number of serotonin-immunoreactive neurons and fibers, but only a few AVP-immunoreactive fibers and VIP-immunoreactive neurons and fibers. On the other hand, numerous AVP- and VIP-immunoreactive neurons and fibers were found in the SCN of the anterior hypothalamic graft. Outgrowing serotonin-immunoreactive fibers from the raphe tissue were densely distributed in the anterior hypothalamic graft. In the SCN, however, only a few fibers were detected. The results demonstrate that the isolated anterior hypothalamic grafts can be innervated by the serotonergic neurons from the raphe grafts, but the innervation pattern of these fibers was quite different from the normal rat. The present results indicate that the isolated SCN has an inhibitory influence on the growth of serotonergic fibers.

914 Lordosis inhibiting systems in the female rat: Functional relationships between dorsal raphe nucleus and gaba neurons

914 Lordosis inhibiting systems in the female rat: Functional relationships between dorsal raphe nucleus and gaba neurons

Evidence for projections from medullary nuclei onto serotonergic and dopaminergic neurons in the midbrain dorsal raphe nucleus of the rat.

The anterograde tracer Phaseolus vulgaris-leucoagglutinin was injected into the medial nucleus of the solitary tract and into the rostral dorsomedial medulla. A sequential two-color immunoperoxidase staining was accomplished in order to demonstrate the co-distribution of presumed terminal axons with chemically distinct neurons in the dorsal raphe nucleus of the midbrain central gray, i.e., B7 serotonergic and A10dc dopaminergic neurons. Black-stained efferent fibers from the medial nucleus of the solitary tract and the rostral dorsomedial medulla intermingled with brown-stained serotonergic (5-hydroxytryptamine-immunoreactive) or dopaminergic (tyrosine hydroxylase-immunoreactive) neurons. Light microscopy revealed that the black-stained efferent axons exhibited numerous en passant and terminal varicosities that were often found in close apposition to brown-stained serotonergic and dopaminergic somata, and to proximal and distal dendrites and dendritic processes. The close association of immunoreactive elements suggests the presence of axo-somatic and axo-dendritic synaptic contacts of medullary fibers with serotonergic and dopaminergic neurons in the dorsal raphe nucleus. These projections could be involved in the modulation of dorsal raphe neurons, depending on the autonomic status of an animal.

Neurochemical afferents controlling the activity of serotonergic neurons in the dorsal raphe nucleus: microiontophoretic studies in the awake cat

Serotonergic (5-HT) neurons of the brainstem dorsal raphe nucleus (DRN) have been implicated in a diversity of physiological and behavioral processes in vertebrates. However, despite extensive information about the intrinsic properties and the efferent projections of this neurochemical system, little information is available regarding the afferents that control its activity. This study investigated the neurotransmitters that regulate the activity of DRN-5-HT neurons under physiologically relevant conditions, by utilizing microiontophoresis in combination with single-unit recordings in the awake, head-restrained cat. This made it possible to examine the direct effects of neurotransmitters on DRN-5-HT neuronal activity, and, through the use of specific antagonists, to study the roles of these neurotransmitter inputs during physiological conditions that influence DRN-5-HT neuronal activity. The results indicate that (1) iontophoretic application of the GABA antagonist bicuculline reversed the typical suppression of neuronal activity seen during slow wave sleep, but had no effect on maintained activity during wakefulness. The suppression of neuronal activity during REM sleep was generally unaffected by application of bicuculline. This suggests a role for a GABAergic input to DRN-5-HT neurons in controlling some aspects of their state-dependent activity. (2) Iontophoretic application of the excitatory amino acid (EAA) antagonist kynurenic acid reduced the magnitude of the neuronal response evoked by phasic auditory stimuli, but had no effect on the spontaneous activity of these neurons, suggesting a role for an EAA input to the DRN in mediating the response to phasic sensory stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of peptidergic efferents from the lateral parabrachial nucleus to identified neurons in the rat dorsal raphe nucleus

The peptidergic content of the lateral parabrachial nucleus (LPB) efferents to the dorsal raphe nucleus (DRN) was studied by combining visualization of the anterogradely transported tracer Phaseolus vulgaris leucoagglutinin within fibers that were immunocytochemically stained for neurotensin (NT), calcitonin gene-related peptide (CGRP) or galanin (GAL). The identity of DRN target neurons was determined with simultaneous immunocytochemical labelling for serotonin, the major transmitter within the nucleus. Within the DRN, we estimated that about two-thirds of the anterogradely labelled fibers arising from the LPB also showed peptidergic immunoreactivity. NT was the most commonly observed neuropeptide in LPB neuronal efferents directed to the DRN, followed by CGRP and GAL. The peptidergic afferents in the DRN were oriented preferentially in the dorsoventral plane. Peptidergic fibers from the LPB possessed varicosities (diameters not exceeding 3 μm) and were apposed on serotoninergic neuronal somata. Some of the anterogradely labelled peptidergic fibers were not associated with cells showing immunoreactivity for serotonin. The present results suggest that NT-ergic, CGRP-ergic and GAL-ergic neurons within the LPB are in contact with serotoninergic and non-serotoninergic neurons within the DRN. Since the DRN is known to project to the LPB, it is likely that bi-directional interconnections between these nuclei exist. Such linkages may provide anatomical substrates for coordinated autonomic responses.

Substance P injection into the dorsal raphe increases blood pressure and serotonin release in hippocampus of conscious rats

Microinjections of substance P (SP, 100 pmol) into the dorsal raphe nucleus (DRN) in conscious rats increased blood pressure and heart rate for 30–40 min. Concomitantly, the extracellular levels of 5-hydroxytryptamine (5-HT) in the ventral hippocampus, monitored by microdialysis, increased by 30% for 20 min compared with the vehicle control. Pretreatment with the 5-HT 2 receptor antagonist, ritanserin (1 mg/kg i.v.), prevented the pressor response to SP but not the increase in heart rate. Pretreatment with the partial 5-HT 1A receptor agonist, 8-methoxy-2-(N-2-chloroethyl-N-n-propyl)amino tetralin (8-MeO-CLEPAT, 10 μg/kg i.v.) prevented the increase in both blood pressure and heart rate. It is suggested that microinjections of SP into the DRN increase blood pressure through activation of serotonergic DRN neurons and that the postsynaptic receptor responsible for the pressor response is of the 5-HT 2 type.

Distribution, morphology and number of monoamine-synthesizing and substance P-containing neurons in the human dorsal raphe nucleus

The distribution, morphology and number of serotonin-, catecholamine- and substance P-containing neurons in the human dorsal raphe nucleus were studied. Parallel series of sections were prepared from 10 human brainstems obtained at autopsy from palients without neurological disease aged between 42 and 88 years. The neurons were identified using immunohistochemistry with antibodies raised against phenylalanine hydroxylase (tryptophan hydroxylase-containing, serotonin neurons), tyrosine hydroxylase (catecholamine neurons) and substance P.A reference series of Nissl-stained sections was also prepared and data published separately were used to delineate the subnuclear divisions of the dorsal raphe nucleus and to establish the total number of neurons in each subnucleus. The following principal findings emerged. (1) Serotonin-synthesizing neurons are present in all regions of the dorsal raphe nucleus and their total number is165,000 ± 34,000. The same types of neurons as those seen in Nissl material characterize each of the five subnuclei (caudal, dorsal, ventral, ventrolateral and interfascicular). (2) Substance P-containing neurons mostly occupy the rostral part of the nucleus and their number is74,600 ± 17,600. (3) Catecholamine cells are only found in the rostral part of the dorsal raphe nucleus and their number is5600 ± 3400. (4) In the ventral and interfascicular subnuclei the combined number of serotonin-synthesizing and substance P-containing neurons exceeds the total number of Nissl-stained neurons suggesting that serotonin and substance P co-exist in a substantial part of the cell population of the dorsal raphe nucleus. This is further supported by the highly similar morphology and size of these neurons. It is concluded that there are demonstrable chemical differences between the various subregions of the human dorsal raphe nucleus. These differences are in harmony with the results of hodological studies in animals, which have demonstrated differential projection pathways emerging from this nucleus.

K + channel and 5-hydroxytryptamine 1A autoreceptor interactions in the rat dorsal raphe nucleus: An in vitro electrophysiological study

Extracellular recordings were made from serotonergic neurons of the rat dorsal raphe nucleus in a slice preparation. In the presence of phenylephrine (3 μM) to restore the pacemaker activity of otherwise silent serotonergic neurons, superfusion with the 5-hydroxytryptamine 1A agonist ipsapirone depressed the firing of these neurons with an ic 50 of ~50 nM. Complete inhibition was achieved with 100–300 nM of the drug. Concomitant superfusion with the 5-hydroxytryptamine 1A antagonists spiperone (100 nM) or propranolol (10 μM) markedly reduced the inhibitory effect of ipsapirone (100 nM). Superfusion with K + channel blockers such as apamin (50–100 nM), charybdotoxin (100 nM) or Ba 2+ (1 mM) did not induce any changes in the electrical activity of serotonergic neurons. However, 4-aminopyridine (0.1–1 mM) disrupted the regularity of their discharge without affecting the mean firing rate. The ipsapirone-induced inhibition was unchanged by apamin and charybdotoxin, but was markedly reduced by Ba 2+ and 4-aminopyridine. Thus the ic 50 of ipsapirone was shifted to ~150 nM in the presence of 1 mM of 4-aminopyridine. These results indicate that, in serotonergic neurons within the dorsal raphe nucleus, the K + channel opened through the stimulation of 5-hydroxytryptamine 1A autoreceptors is 4-aminopyridine-sensitive.

Single-unit responses of serotonergic neurons to vasoactive drug administration in behaving cats

Single-unit activity of serotonergic neurons in the dorsal raphe nucleus (DRN), heart rate (HR), and arterial blood pressure were recorded in freely moving cats during spontaneous behavior and in response to systemic administration of vasoactive drugs. The activity of serotonergic neurons varied in association with behavioral arousal but was unrelated to spontaneous fluctuations in HR and blood pressure. Bolus administration of phenylephrine hydrochloride and sodium nitroprusside (15-20 micrograms/kg iv) produced a rapid transient increase (35 mmHg) and decrease (49 mmHg), respectively, in mean arterial pressure (MAP). Infusion of phenylephrine and sodium nitroprusside (100 micrograms/ml) produced sustained hypertension (avg MAP 166 mmHg) and hypotension (avg MAP 49 mmHg), respectively. The activity of serotonergic neurons was not significantly altered in response to phenylephrine or sodium nitroprusside administration. Furthermore, no significant changes in unit activity were observed after hydralazine administration (1 mg/kg iv) despite prolonged reflex activation of sympathetic outflow. Thus the activity of DRN serotonergic neurons was unrelated to transient alterations in blood pressure and baroreceptor activity. These results suggest that changes in the activity of serotonergic DRN neurons are not involved in physiological mechanisms underlying reflex alterations in sympathetic (and parasympathetic) outflow invoked by hypertension and hypotension.