The coexistence of TrkA with putative transmitter agents and calcium-binding proteins in the vagal and glossopharyngeal sensory neurons of the adult rat

The presence of the neurotrophin receptor, TrkA, in neurochemically identified vagal and glossopharyngeal sensory neurons of the adult rat was examined. TrkA was colocalized with calcitonin gene-related peptide (CGRP), parvalbumin, or calbindin D-28k in neurons of the nodose, petrosal and/or jugular ganglia. In contrast, no TrkA-immunoreactive (ir) neurons in these ganglia colocalized tyrosine hydroxylase-ir. About one-half of the TrkA-ir neurons in the jugular and petrosal ganglia contained CGRP-ir, whereas only a few of the numerous TrkA-ir neurons in the nodose ganglion contained CGRP-ir. Although 43% of the TrkA-ir neurons in the nodose ganglion contained calbindin D-28k-ir, few or no TrkA-ir neurons in the petrosal or jugular ganglia were also labeled for either calcium-binding protein. These data show distinct colocalizations of TrkA with specific neurochemicals in vagal and glossopharyngeal sensory neurons, and suggest that nerve growth factor (NGF), the neurotrophin ligand for TrkA, plays a role in functions of specific neurochemically defined subpopulations of mature vagal and glossopharyngeal sensory neurons.     

ACh and ATP mediate excitatory transmission in cat carotid identified chemoreceptor units in vitro

Several molecules have been proposed as excitatory transmitters between glomus (type 1) cells and nerve terminals of petrosal ganglion (PG) neurons in the carotid body (CB). We tested whether ACh and ATP have a role to play as excitatory transmitters in the cat CB by recording intracellularly from identified PG neurons functionally connected to the CB in vitro. PG neurons projecting to the CB were classified according to their intracellular responses as: (a) neurons with humped action potentials (hAP neurons) responding phasically to long-lasting depolarizing pulses (53/67), and (b) neurons with smooth action potentials (non-hAP neurons) that fire tonically during long-lasting depolarizations (14/67). CB stimulation by stop flow and/or acidosis induced activity in 28 of 39 hAP-type neurons, being classified as chemosensory, but in none of the non-hAP neurons. Hexamethonium (10 microM) and suramin (100 microM) reversibly abolished the increased discharges evoked in chemosensory neurons (8/9) by stop flow or acidosis. Moreover, 24 of 27 chemosensory neurons responded to ganglionar application of ACh and ATP, while two neurons responded only to ACh and one to ATP. Mechanical deformation of the carotid sinus induced firing activity in 10 of 13 non-hAP neurons, but in none of the hAP neurons tested. Interestingly, 4/10 non-hAP neurons, which responded to carotid sinus mechanical stimulation also responded to ganglionar application of ATP, but were insensitive to ACh. Present results favor the hypothesis that ACh and ATP are excitatory transmitters in the cat CB, acting-at least-on the PG neuron terminals in the CB.     

Selective activation of carotid nerve fibers by acetylcholine applied to the cat petrosal ganglion in vitro

The petrosal ganglion innervates carotid body chemoreceptors through the carotid (sinus) nerve. These primary sensory neurons are activated by transmitters released from receptor (glomus) cells, acetylcholine (ACh) having been proposed as one of the transmitters involved in this process. Since the perikarya of primary sensory neurons share several properties with peripheral sensory endings, we studied the electrical responses of the carotid nerve and glossopharyngeal branch to ACh locally applied to the cat petrosal ganglion superfused in vitro. Ganglionar applications of AChCl (1 μg−1 mg) generated bursts of action potentials conducted along the carotid nerve, while only a few spikes were exceptionally recorded from the glossopharyngeal branch in response to the largest doses. Carotid nerve responses to ACh were dose-dependent, the higher doses inducing transient desensitization. Application of nicotine to the petrosal ganglion also evoked dose-dependent excitatory responses in the carotid nerve. Responses to ACh were reversibly antagonized by adding hexamethonium to the superfusate, more intense and prolonged block of ACh responses being produced by mecamylamine. Ganglionar applications of γ-amino butyric acid and serotonin, in doses of up to 5 mg, did not induce firing of action potentials in any of the branches of the glossopharyngeal nerve. Our results indicate that petrosal ganglion neurons projecting through the carotid nerve are selectively activated by ACh acting on nicotinic ACh receptors located in the somata of these neurons. Thus, cholinosensitivity would be shared by the membranes of peripheral endings and perikarya of primary sensory neurons involved in arterial chemoreception.     

Coexistence of S100β and putative transmitter agents in vagal and glossopharyngeal sensory neurons of the rat

The coexistence of S100β with calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM), nicotinamide adenosine dinucleotide phosphate-diaphorase (NADPH-d), and tyrosine hydroxylase (TH) was examined in the glossopharyngeal and vagal sensory ganglia. S100β immunoreactive (-ir) neurons in the jugular and petrosal ganglia frequently colocalized CGRP- or SP-ir, whereas S100β-ir neurons in the nodose ganglion infrequently contained CGRP- or SP-ir. No S100β-ir neurons in the jugular and petrosal ganglia showed SOM-ir while the small number of SOM-ir neurons in the nodose ganglion colocalized S100β-ir. Many neurons in the nodose ganglion colocalized S100β-ir and NADPH-d activity, whereas S100β-ir neurons in the jugular and nodose ganglia infrequently contained NADPH-d activity. S100β- and TH-ir were frequently colocalized in nodose ganglion but not in petrosal or jugular ganglion neurons. These findings suggest relationships between S100β and specific putative transmitters in functions of subpopulations of vagal and glossopharyngeal sensory neurons.     

Neurotrophins alter the numbers of neurotransmitter-ir mature vagal/glossopharyngeal visceral afferent neurons in vitro

Mature nodose and petrosal ganglia neurons (placodally derived afferent neurons of the vagal and glossopharyngeal nerves) contain TrkA and TrkC, and transport specific neurotrophins [nerve growth factor (NGF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4)]. This study evaluated neurotrophin influences on the presence of neuropeptides and/or neurotransmitter enzymes in these visceral sensory neurons. NGF, NT-3 and NT-4 (10–100 ng/ml) were applied (5 days) to dissociated, enriched, cultures of mature nodose/petrosal ganglia neurons, and the neurons processed for tyrosine hydroxylase (TH), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and neurofilament (NF-200) immunocytochemistry. Addition of NGF to nodose/petrosal ganglia neuron-enriched cultures significantly increased the number of TH-immunoreactive (ir) neurons, decreased the number of VIP-ir neurons in the cultures, and did not affect the numbers of CGRP-ir neurons. The addition of an NGF neutralizing antibody attenuated the effects of NGF on TH and VIP-ir neurons. NT-3 increased the number of VIP-ir neurons in the nodose/petrosal ganglia cultures and did not alter the numbers of TH-, or CGRP-ir neurons. The addition of an NT-3 neutralizing antibody attenuated the effects of NT-3 on VIP-ir neurons. NT-4 had no significant effects on the numbers of TH, VIP and CGRP-ir neurons. The absence of neurotrophin-induced changes in the numbers of NF-200-ir neurons in culture showed the lack of neurotrophin-mediated changes in survival of mature vagal afferent neurons. These data demonstrate that specific neurotrophins influence the numbers of neurons labeled for specific neurochemicals in nodose/petrosal ganglia cultures. These data, coupled with previous evidence for the presence of TrkA and TrkC mRNA and of the retrograde transport of NGF and NT-3, suggest important roles for NGF and NT-3 in the maintenance of transmitter phenotype of these mature visceral afferent neurons.     

The distribution of the cat''s carotid sinus nerve afferent and efferent cell bodies using the horseradish peroxidase technique

The location of both afferent and efferent carotid sinus nerve (CSN) cell bodies in the cat has been determined using the horseradish peroxidase (HRP) technique. Following a limited exposure of the central cut end of the CSN to HRP, labeled sensory ganglion cells were found in both the petrosal and superior ganglia of the IXth cranial nerve. An average of 387 in the former and 16 cells in the latter ganglion were labeled.

Retrogradely labeled neurons were found only within the ipsilateral medulla. These cells were both round and spindle shaped and had an average somal diameter of 19 μm. The number of these CSN efferent cell bodies ranged from 1 to a maximum of 20 in a given animal. They were found in both the nucleus parvocellularis and the retrofacial nucleus. In 8 cases axonal labeling was observed. Axons generally projected dorsomedially from the ventrolateral medulla.     

Coexistence of calbindin D-28k and NADPH-diaphorase in vagal and glossopharyngeal sensory neurons of the rat

The presence and coexistence of calbindin D-28k-immunoreactivity (ir) and nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase activity (a marker of neurons that are presumed to convert L-arginine to L-citrulline and nitric oxide) were examined in the glossopharyngeal and vagal sensory ganglia (jugular, petrosal and nodose ganglia) of the rat. Calbindin D-28k-ir nerve cells were found in moderate and large numbers in the petrosal and nodose ganglia, respectively. Some calbindin D-28k-ir nerve cells were also observed in the jugular ganglion. NADPH-diaphorase positive nerve cells were localized to the jugular and nodose ganglia and were rare in the petrosal ganglion. A considerable portion (33–51%) of the NADPH-diaphorase positive neurons in these ganglia colocalized calbindin D-28k-ir. The presence and colocalization of calbindin D-28k-ir and NADPH-diaphorase activity in neurotransmitter-identified subpopulations of visceral sensory neurons were also studied. In all three ganglia, calcitonin gene-related peptide (CGRP)-ir was present in many NADPH-diaphorase positive neurons, a subset of which also contained calbindin D-28k-ir. In the nodose ganglion, many (42%) of tyrosine hydroxylase (TH)-ir neurons also contained NADPH diaphorase activity but did not contain calbindin D-28k-ir. These data are consistent with a potential co-operative role for calbindin D-28k and NADPH-diaphorase in the functions of a subpopulation of vagal and glossopharyngeal sensory neurons.     

Effects of peripheral axotomy of the inferior alveolar nerve on the levels of neuropeptide Y in rat trigeminal primary afferent neurons

The effects of peripheral axotomy of the inferior alveolar nerve (IAN) on the presence and distribution of neuropeptide Y (NPY)-like immunoreactivity (IR) in the trigeminal sensory nuclear complex (TSNC) and trigeminal ganglion were investigated in the rat by immunohistochemistry. In the normal trigeminal ganglion, there were no NPY-IR cells, and some perivascular nerve fibres exhibited NPY-IR. In normal TSNC, many NPY-IR axons and nerve terminals were observed in the superficial layers of the subnucleus caudalis (SpVc) and paratrigeminal nucleus (paraV), but were sparse in the other subnuclei of the TSNC. Fourteen days following peripheral axotomy of the IAN, many large- and medium-sized cells in the trigeminal ganglion displayed NPY-IR, and marked increases in the numbers and staining densities of NPY-IR were observed in deeper laminae (laminae III-V) of the dorso-medial region of the SpVc and other nuclei, in addition to the dorso-medial region of the spinal trigeminal tract. Degrees of alterations of the levels of NPY were most marked in the SpVc. The present results indicate that peripheral axotomy of the IAN evokes the appearance of NPY-IR in the trigeminal ganglion and alterations of NPY-IR in the entire IAN projection areas of the TSNC.     

Evidence for a dopaminergic innervation of the subthalamic nucleus in the rat

The dopaminergic connection from the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA) to the subthalamic nucleus in the rat was investigated using anterograde retrograde tracers. Iontophoretic injection of the retrograde tracer fluoro-gold (FG) into the subthalamic nucleus resulted in a substantial number of labeled neurons in the SNc. Immunohistochemistry of tyrosine hydroxylase (TH) confirmed the dopaminergic nature of these labeled neurons. Retrogradely labeled neurons were also found in the VTA. Injection of the anterograde tracer biocytin into the SNc produced biocytin-labeled terminals in the subthalamic nucleus hence providing clear evidence for a dopaminergic innervation of this nucleus. Quantitative analysis of labeled axons revealed that there were 15–38 terminal branches per axon, each branch being 50–150 μm long. The overall dimensions of one terminal arborization were 400 × 250 × 150 μm. There was no clear-cut topographical organization of the projection, but a slight mediolateral difference in the density of terminals. This direct dopaminergic projection is thought to interact with cortical and pallidal inputs in the subthalamic nucleus, which implies that the functions of the subthalamic nucleus are more complex than previously assumed.     

Differential regulation of tyrosine hydroxylase protein and activity in rabbit sympathetic neurones after long-term cold exposure: altered responses in ageing

The aim of this study was to investigate the response of sympathetic neurones to prolonged neural stimulation, using cold exposure as a non-invasive experimental paradigm. We examined the effects of prolonged (8 days and 4 wk) cold exposure on tyrosine hydroxylase (TH) protein and activity and neuropeptide Y (NPY) levels in sympathetic neurones of the superior cervical ganglion (SCG), together with NPY levels in the ear artery from young and aged rabbits. The main findings were as follows. In young rabbits, TH levels and TH activity were differentially regulated in response to prolonged cold exposure. TH levels rose whilst TH activity tended to decline. Decentralization of SCG from young animals before cold exposure abolished the rise in TH levels. TH activity in SCG from young rabbits was reduced by decentralization whilst cold exposure resulted in an increase in TH activity. Thus, TH activity was induced in the SCG in the absence of pre-ganglionic input, demonstrating a non-synaptic regulatory mechanism. In old rabbits, cold-induced changes were either delayed or failed to occur, indicating that the responses of sympathetic neurones to cold stress are impaired in old age.     

Immunohistochemical and biochemical analysis of serotonin and substance P colocalization in the nucleus tractus solitarii and associated afferent ganglia of the rat

In a previous study of afferent projections to the nucleus tractus solitarii (NTS), it was shown that over half of the retrogradely-labelled neurons in the nucleus raphe pallidus contained serotonin-immunoreactivity and over half of these neurons contained substance P-immunoreactivity, suggesting that these two putative neurotransmitters are colocalized in NTS-afferent neurons. The objectives of the present study were to 1) directly determine if varicosities in the NTS, the area postrema (AP), and the dorsal motor nucleus of the vagus nerve (DMN) do contain both transmitters, 2) determine if primary afferent neurons in the nodose and pretrosal ganglia might also colocalize serotonin and substance P, and 3) quantify the amount of substance P that is contained in serotonergic varicosities in the NTS. Distributions and colocalization of substance P and serotonin in the NTS were studied using dual-color immunohistochemistry, while the quantity of substance P in serotonergic varicosities was assessed by radioimmunoassay (RIA) using micropunches from the NTS of 5,7-dihydroxytryptamine-(5,7 DHT-) and vehicle-treated rats. Varicosities that contained both serotonin- and substance P-immunoreactivity were found in the NTS, the DMN, and the AP. Double-labelled varicosities were common in the NTS and DMN (i.e., qualitatively similar to the density seen in the hypoglossal nucleus and in the ventral horn of the cervical spinal cord); however, the vast majority of the varicosities in these autonomic areas only displayed immunoreactivity for one or the other of these transmitters. This paucity of doubly-labelled varicosities, in comparison to the number of singly-labelled varicosities, was reflected in the lack of a significant decrease in substance P levels as determined by RIA of micropunches taken from caudal and intermediate levels of the NTS in 5,7 DHT- and vehicle-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Value of non-invasive continuous blood pressure monitoring in the detection of carotid sinus hypersensitivity

A patient with recurrent episodes of dizziness and blackouts is described. Detailed cardiac and neurological investigations were normal. Autonomic assessment excluded postural hypotension and confirmed normal sympathetic vasoconstrictor function. Cardiac parasympathetic function in response to deep breathing, hyperventilation and ocular pressure was normal. Left carotid sinus massage only reproducibly lowered blood pressure with minimal change in heart rate. This occurred mainly during head-up tilt. The fall in blood pressure was not affected by the muscarinic blocker atropine, or the peptide release inhibitor, octreotide. A diagnosis of left carotid sinus hypersensitivity of the vasodepressor variety was made. Left carotid sinus denervation was performed. This successfully prevented further episodes of dizziness and blackouts. The ability to measure beat-to-beat blood pressure non-invasively was of particular importance in diagnosis, and in the assessment of management options in this patient.     

Contribution of dopamine neurons in the medial zona incerta to the innervation of the central nucleus of the amygdala, horizontal diagonal band of Broca and hypothalamic paraventricular nucleus

Results of previous studies suggested that incertohypothalamic dopamine (IHDA) neurons located in the medial zona incerta (MZI) project to the central nucleus of the amygdala (cAMY), horizontal diagonal band of Broca (HDB), and paraventricular nucleus (PVN). The overall goal of the present study was to determine the relative contribution of IHDA neurons to the DA innervation of these brain regions. A combined fluorescent and in situ hybridization histochemical procedure was employed to localize the retrograde tracer fluoro-gold (FG) in cells expressing tyrosine hydroxylase (TH) mRNA in the MZI following its iontophoretic injection into either the cAMY, HDB or PVN. For comparison, the numbers of dual labeled FG/TH mRNA neurons in the midbrain were also determined. One week after unilateral injection of FG into the cAMY, cells containing FG+TH mRNA were found in the ipsilateral MZI, substantia nigra zona compacta (SNC) and ventral tegmental area (VTA). The total numbers of cells labeled with FG varied with the size of the injection site, but the ratio of dual labeling in the MZI to that of the SNC–VTA remained constant across animals at approximately 1:6. FG injections into the HDB resulted in a ratio of dual labeled cells in the ipsilateral MZI and VTA of approximately 1:2, but no dual labeled cells were found in the SNC. Dual labeled cells were only found in the ipsilateral MZI in animals receiving FG injections in the PVN. Thus, DA terminals in the PVN originate exclusively from IHDA neurons in the MZI, whereas these neurons provide only a portion of the DA innervation of the cAMY and HDB. The similar distribution of dual labeled cells in the MZI following FG injections into the cAMY, HDB and PVN suggests that perikarya of IHDA neurons projecting to these regions are not organized into distinct groups.     

The projections to the medulla of neurons innervating the carotid sinus in the dog

The localization and brain stem projections of neurons innervating the carotid sinus of the dog were studied by horseradish peroxidase histochemistry following microinjection of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) under the adventitia of the carotid sinus. Within the brain stem, labeled afferent fibers and presumptive terminals were found bilaterally in the caudal nucleus tractus solitarius (nTS), the area postrema (AP), and the lateral tegmental field (LTF), reaching the area of the nucleus ambiguus (nA). Sparse labeling was also seen in the ipsilateral spinal trigeminal nucleus (SpV) and lateral cuneatus nucleus (LCn). These findings suggest the existence of multiple pathways by which peripheral baroreceptor inputs may influence central cardiovascular-related neurons. In addition to classically defined relay in the nTS, carotid sinus afferents may also interact more directly with these neurons in other brain stem regions.     

Pattern of inhibition of parasympathetic activity in response to incremental bolus doses of atropine in carotid sinus hypersensitivity

Patients with established reproducible cardioinhibitory carotid sinus hypersensitivity were studied to define the dose of atropine required to abolish the heart rate slowing in response to carotid sinus massage, the heart rate response to the Valsalva manoeuvre and salivary gland flow. Bolus doses of intravenous atropine were given to a cumulative dose of 700 mcg. Cardioinhibition was abolished in all patients with a total dose of 700 mcg. The heart rate ratio during the Valsalva manoeuvre did not vary significantly. The decline in salivary gland flow was evident earliest, at a dose of 75 mcg. In clinical studies, 700 mcg of atropine will abolish the diagnostic cardioinhibitory response to carotid sinus massage in patients with the syndrome. This may not prevent syncope, as could occur in the key frequent vasodepressor form of carotid sinus hypersensitivity syndrome.     

High-resolution real-time ultrasound of the carotid bifurcation in patients with hyperactive carotid sinus syndrome

Summary The carotid bifurcations and the common carotid arteries of 36 patients with the diagnosis hyperactive carotid sinus syndrome (HCSS) were investigated by continuous wave (CW) Doppler ultrasonography and high-resolution real-time B-scan. Using these non-invasive tests, the functional impact of luminal stenosis and the morphological changes resulting from arteriosclerotic deformities could be established. Significant differences were found in comparison with a reference group of 199 patients with a high risk of arteriosclerosis. In the HCSS group, 5 patients had a stenosis of more than 50% at the origin of the internal carotid artery on both sides, or on one side in combination with large plaques or a complete occlusion on the contralateral side. Seventy-five per cent of patients in the HCSS group, as compared to only 23.5% of the control group, had effective arteriosclerotic changes in the carotid bifurcation on both sides; 4 patients had such changes only unilaterally. Marked additional bilateral arteriosclerotic depositions were detected in the common carotid arteries of 17 patients (47.2%). In 5 patients no arteriosclerotic lesions were detectable in the carotid bifurcations, but marked changes were found in both common carotid arteries. These data indicate that bilateral arteriosclerotic changes in the carotid bifurcations and/or the common carotid arteries represent an important pathophysiological factor for the development of an HCSS.Supported by the Landesamt für Wissenschaft und Forschung Nordrhein-Westfalen     

不同程度颈动脉狭窄大鼠模型建立及脑内单胺类递质变化的研究

周振华,陈康宁,黄河清,周宇,范文辉,李露斯摘要:目的制作一种新的不同狭窄程度的大鼠颈动脉狭窄模型,观察重度颈动脉狭窄大鼠学习能力及脑内单胺类神经递质含量的变化。方法采用“针控线拴法”,通过调整针的型号来制作不同狭窄程度的大鼠颈动脉狭窄模型,观察重度颈动脉狭窄大鼠水迷宫定位航行试验并用高效液相色谱法测定大鼠脑内单胺类神经递质含量的变化。结果成功制作了轻、中、重不同狭窄的颈动脉狭窄模型;各时相点水迷宫定位航行试验中重度颈动脉狭窄大鼠较假手术对照组逃避潜伏期明显延长(P<0.01);除1月、2月重度颈动脉狭窄组DA与假手术对照组相比无显著性差异外(P>0.05),其余时相点重度颈动脉狭窄组NE、5-HT、DA含量与假手术对照组相比均显著降低(P<0.01)。结论针控线拴法能成功建立不同狭窄程度的大鼠颈动脉狭窄模型,重度颈动脉狭窄大鼠学习能力受损且脑内单胺类神经递质含量降低。     

Mesolimbic dopaminergic neurons innervating the hippocampal formation in the rat: a combined retrograde tracing and immunohistochemical study

A major mesolimbic projection towards the hippocampal formation (HF) has been extensively described, but no clear evidence of its dopaminergic content has been demonstrated. In order to evaluate the percentage of dopaminergic (DA) cells of ventral tegmental area (VTA-A10) and adjacent substantia nigra (SN-A9) projecting to the HF, the retrograde neuronal tracer technique was combined with the tyrosine hydroxylase (TH) immunocytochemistry. Fluoro-gold (FG) was injected in several areas (subiculum, CA1, CA3, dentate gyrus) of either septal and temporal HF. Sections containing retrogradely FG labeled neurons were either mounted directly as controls or incubated with TH antiserum and revealed with rhodamine. The quantitative evaluation of retrogradely labeled and TH-IR stained cells showed that both VTA and SN projections towards the HF are partially (15–18%) dopaminergic. Ten percent of the DA neurons of the VTA projected to contralateral HF, whereas none did in the SN. In conclusion, the temporal HF (mainly subiculum and adjacent CA1) appears to receive the main DA afferents from both VTA cells and medial half of SN, pars compacta, whereas the septal HF (particularly CA1) receives its DA input from neurons located in the ventral half and in the upper and lower borders of the VTA.     

Study of possible transmitters in the solitary tract nucleus of the cat involved in the carotid sinus baro- and chemoreceptor reflex

By using a multibarrelled microelectrode, the possibility that putative transmitters may influence on the field potential evoked in the solitary tract nucleus by electrical stimulation of the carotid sinus nerve (the NTS response) was examined electrophysiologically in the cat. After iontophoretic application of a selective antagonist to the putative transmitter, it was determined whether or not the NTS response was influenced. Both substance P antagonist and naloxone altered the NTS response recorded in the depressor and apneic (or hypopneic) response zone as well as in the pressor and apneustic (or inspiratory) response zone throughout the rostral, intermediate and commissure regions, suggesting that substance P and opioid peptide may play the role of excitatory transmitters. Under the polarizing cathodal current which may activate inhibitory inputs to the site of the NTS response, bicuculline and prazosin strongly enhanced the NTS response recorded in the pressor and apneustic zone, while naloxone weakly enhanced the NTS response recorded in the depressor and apneic zone. These results suggest that gamma-aminobutyric acid, alpha-adrenergic agonist and opioid peptide may have an inhibitory influence on the NTS response.