Bilateral vagotomy differentially alters the magnitude of hypoglossal and phrenic long-term facilitation in anesthetized mechanically ventilated rats

Acute intermittent hypoxia elicits long-term increases in respiratory motor output (long-term facilitation, LTF). Most investigators study LTF in mechanically ventilated, bilaterally vagotomized, and anesthetized animals. Vagotomy blocks inhibitory lung-volume feedback that could diminish the magnitude of LTF. However, the effects of vagotomy on LTF may not be so straight forward. In cats, vagotomy increases LTF of upper airway muscles but may decrease LTF of accessory pump muscles. The effects of vagotomy on LTF in rats are unknown. We hypothesized that the magnitude of hypoglossal and phrenic LTF would be differentially regulated by vagal afferent feedback in anesthetized and mechanically ventilated rats. Hypoglossal and phrenic motor outputs were recorded from vagotomized and vagally intact anesthetized mechanically ventilated adult Sprague-Dawley rats before, during, and up to 60-min after intermittent hypoxia. Ventilator frequency (f), pump volume, and peak tracheal pressure were not different between groups. The effects of vagotomy on the magnitude of LTF depended on the motoneuron population in question. The magnitude of hypoglossal LTF increased after vagotomy (vagi intact, -5+/-10%; vagotomy, 66+/-11% above baseline; p<0.05); whereas, the magnitude of phrenic LTF decreased after vagotomy (vagi intact, 135+/-24%; vagotomy, 40+/-13% above baseline; p<0.05). These data support previous work in anesthetized cats, and suggest that the expression of hypoglossal and phrenic respiratory motor plasticity is differentially regulated by vagal afferent feedback.     

Augmented breaths (‘sighs’) are suppressed by morphine in a dose-dependent fashion via naloxone-sensitive pathways in adult rats

Morphine treatment can eliminate augmented breaths (ABs; ‘sighs’) during spontaneous breathing. In the present study, unanesthetized rats were studied to: (1) determine the involvement of naloxone-sensitive receptor pathways, and (2) establish the dose–response relationship of this side effect. At a dosage of 5 mg/kg (2–10 mg/kg is recommended range for analgesia) morphine eliminated ABs from the breathing rhythm across nearly 100 min post-administration (vs. 6.2 ± 1.6 ABs in 15 min, control condition, p < 0.001). This occurred despite no apparent effect on indices of ventilation. By contrast, when naloxone was co-administered with morphine, the occurrence of ABs was not different compared to control. The suppression of ABs by morphine followed a sigmoidal pattern across the low–mid dosage range (R² = 0.83), whereas tidal volume and breathing frequency were unaffected. We conclude that the opioid-induced suppression of ABs is mediated by naloxone-sensitive opioid receptor pathways, and that this side effect is potent across the low–mid dosage range, and cannot be simply avoided by restricting dosage.     

The role of augmented breaths (sighs) in bronchial asthma attacks

Summary In an attempt to test the hypothesis whether adenosine is involved in the regulation of coronary flow, adenosine, inosine and hypoxanthine were measured in the effluent perfusate and in the tissue of isolated guinea pig hearts under various experimental conditions. In addition, the release of¹⁴C-adenosine,¹⁴C-inosine and¹⁴C-hypoxanthine was determined after prelabeling cardiac adenine nucleotides with¹⁴C-adenine.The decrease in coronary resistance induced by hypoxic perfusion (30% and 20% in the gas phase) and during autoregulation was associated with a considerable increase in the release of adenosine, inosine and hypoxanthine. Under both conditions the concentrations of adenosine in the effluent perfusate were clearly within the coronary vasodilating range of exogenously administered adenosine. The tissue content of adenosine also increased significantly when the perfusion pressure was reduced. The release of¹⁴C-adenosine closely paralleled the changes in coronary resistance during hypoxic perfusion, autoregulation and during reactive hyperemia. The specific activity of adenosine in the effluent perfusate, however, decreased substantially upon reduction of the oxygen supply to the heart, indicating that the release of¹⁴C-adenosine does not provide an absolute measure of total adenosine release by the heart.Our data indicate that the greater part of the adaptive changes of vascular resistance during hypoxia and autoregulation can be attributed to adenosine which is formed at an enhanced rate under these conditions. However, other factors might be involved as well.A preliminary report of these studies was given at the VI. Annual Meeting of the International Study Group for Research in Cardiac Metabolism, Freiburg i. Br., September 1973 and appeared in Recent advances in studies on cardiac structure and metabolism, Vol. 7, Editors: P. Harris, R. J. Bing, and A. Fleckenstein, pp. 171–175. Urban & Schwarzenberg 1976     

Characteristics of augmented breaths provoked by almitrine bismesylate in cats.

The contribution of almitrine bismesylate to the occurrence and pattern of augmented breaths was studied in fifteen spontaneously breathing, anaesthetized cats. Breathing was via a tracheostomy, while the laryngeal resistance to airflow was measured with the larynx isolated in situ. Almitrine bismesylate at a dose of 0.5 mg kg-1 of body weight was injected intravenously in the intact animals and following bilateral vagotomy which spared the right recurrent laryngeal nerve. Almitrine injected intravenously elicited augmented breaths within the first 45 s in thirteen cats and within 1 min in the remaining two cats. During augmented breaths inspiratory and expiratory airflows rose, the mean increases being 385.2 and 159.6% respectively above the controls (P less than 0.01). The inspiratory laryngeal resistance declined to 77.7% of the control (P less than 0.01) and expiratory laryngeal resistance increased by 95.4% above the control level (P less than 0.01). The inspiratory and expiratory times were prolonged by 56 and 58% compared with baseline breathing. Following the augmented breaths the respiratory airflows exceeded baseline values, the respiratory timing was slightly reduced, and the inspiratory laryngeal resistance was significantly lowered below the control level (P less than 0.01). The expiratory laryngeal resistance showed the same trend without statistical significance. Bilateral vagotomy abolished the occurrence of augmented breaths following almitrine injection.     

Urethane inhibits genioglossal long-term facilitation in un-paralyzed anesthetized rats

For ∼3 decades, urethane has been (partially or solely) used as a successful anesthetic in numerous respiratory long-term facilitation (LTF) studies, which were performed on anesthetized, paralyzed, vagotomized and artificially ventilated animals of several different species. However, things become complicated when LTF of muscle activity is studied in un-paralyzed animals. For example, a commonly used acute intermittent hypoxia (AIH) protocol failed to induce muscle LTF in anesthetized, spontaneously breathing rats. But muscle LTF could be induced when hypoxic episode number was increased and/or anesthetics other than urethane were used. In these studies however, neither anesthetic nor paralysis was mentioned as a potential factor influencing AIH-induced muscle LTF. This study tested whether urethane inhibits AIH-induced genioglossal LTF (gLTF) in un-paralyzed ventilated rats, and if so, determined whether reducing urethane dose reverses this inhibition. Three groups of adult male Sprague–Dawley rats were anesthetized (Group 1: ∼1.6 g kg⁻¹ urethane; Group 2: 50 mg kg⁻¹ α-chloralose +0.9–1.2 g kg⁻¹ urethane; Group 3: 0.9 g kg⁻¹ urethane +200–400 μg kg⁻¹ min⁻¹ alphaxalone), vagotomized and mechanically ventilated. Integrated genioglossus activity was measured before, during and after AIH (5 episodes of 3-min isocapnic 12% O₂, separated by 3-min hyperoxic intervals). The AIH-induced gLTF was absent in Group 1 rats (success rate was only ∼1/7), but was present in Group 2 (in 10/12 rats) and Group 3 (in 11/11 rats) rats. The genioglossal response to hypoxia was not significantly different among the 3 groups. Collectively, these data suggest that urethane dose-dependently inhibits gLTF in un-paralyzed anesthetized rats.     

Opioid μ-receptors in medullary raphe region affect the hypoxic ventilation in anesthetized rats

Opioids can attenuate the peripheral chemoreceptor-mediated hypoxic ventilatory response (HVR) by acting on central μ-type opioid receptors. Since the medullary raphe region (MRR) expresses abundant μ-receptors and participates in modulating HVR, we tested the role of μ-receptors within the caudal, medial, and rostral MRR (cMRR, mMRR, and rMRR) in modulating the HVR. We recorded cardiorespiratory activities and their responses to isocapnic hypoxia in anesthetized rats before and after local microinjection of DAMGO into the MRR, and intravenous administration of DAMGO (100 μg/kg) alone or coupled with a previous local injection of CTAP. Microinjecting DAMGO into the cMRR or mMRR but not the rMRR significantly attenuated the HVR. However, systemic DAMGO-induced HVR attenuation was not significantly affected by pretreating the cMRR and mMRR with CTAP. Our data suggest that cMRR and mMRR μ-receptors are capable of depressing the HVR, while their contribution to the attenuated HVR by systemic DAMGO is limited.     

Respiratory chemoreflexes and effects of cortical activation state in urethane anesthetized rats

Urethane anesthetized (< 1 .3 g/kg), Sprague-Dawley (SD) rats spontaneously cycled between a cortically desynchronized state (State I) and a cortically synchronized state (State III), which were very similar to awake and slow wave sleep (SWS) states in unanesthetized animals, based on EEG criteria. These low levels of urethane anaesthesia did not cause significant respiratory depression or reductions in sensitivity to hypoxia (10% O2 in nitrogen) or hypercapnia (5% CO2 in air) in rats in either State I or State III. Thus, breathing frequency (fR), tidal volume (VT) and total ventilation (VTOT) all increased on cortical activation in urethane-anaesthetized rats whether breathing air, the hypoxic or the hypercapnic gas mixture, in a manner that was very similar to that observed in unanaesthetized animals. The relative sensitivity to hypoxia was greater in State III than State I, the relative sensitivity to CO2, overall, was equal in both states, State III occurred less often during hypoxia and hypercapnia, and hypoxic, urethane-anaesthetized rats sighed frequently, particularly in State I. This is also similar to the situation seen in unanesthetized rats. Given the similarities seen between urethane anesthetized rats in the present study and literature values for unanesthetized rats, the data suggest that urethane-anaesthetized rats provide a good model system for studying respiratory patterns and chemoreflexes as a function of cortical activation state.     

Firing relations of medial septal neurons to the hippocampal theta rhythm in urethane anesthetized rats

Summary On the basis of spontaneous firing patterns and relations to the hippocampal theta rhythm, three cell types were identified within the medial septal nucleus and vertical limb of the nucleus of the diagonal band of Broca (MSN-NDB). In addition to the well known rhythmically bursting cells that fired in bursts on each cycle of the hippocampal theta rhythm, two other cell types are distinguished. Clock cells fired at high rates with a very regular, periodic firing pattern that was unrelated to the theta rhythm. Irregular cells fired at much lower rates, especially during theta rhythm, and had a pseudo-random firing pattern. The firing of irregular cells was often significantly phase-locked to the hippocampal theta rhythm. Crude estimates of the relative proportions of these cell types suggest that the rhythmically bursting cells comprise about 75% of the cells of the MSN-NDB. These three cell types bear a remarkable resemblance, in firing patterns and relative proportions, to the three principal cell types of the medial septal nuclei described in the freely moving rat (Ranck 1976). Measurements of the preferred phases of firing of 128 rhythmically bursting septal neurons (including 22 atropine-resistant and 11 atropine-sensitive cells) indicate that there is no single preferred phase of firing for the population. Rather the distribution of phases over the theta cycle is statistically flat. Variations in recording locations cannot account for this distribution since large differences in preferred phase were found for pairs of cells at the same location. Similarly, plotting only the group of cells identified as projection cells by antidromic activation from the fimbria/fornix, failed to reveal a peak in the distribution. In contrast to the rhythmically bursting cells, the distribution of preferred firing phases for the irregular cells with a significant phase-locking to the theta rhythm did have a clear peak. The peak occurred near the dentate theta rhythm positivity, consistent with the hypothesis that they are driven by feedback from CA1 complex-spike cells.     

Hippocampal theta rhythm and the firing of neurons in walking and urethane anesthetized rats

Summary Recordings were taken from single neurons in the hippocampus and dentate gyrus of rats during walking and urethane anesthesia. Firing histograms for these cells were constructed as a function of the phase of the concurrent extracellularly recorded hippocampal slow wave theta rhythm. Care was taken to be sure of the site of recording of the theta rhythm and its phase with respect to a reliable reference, so that comparisons of the phases of firing could be made across animals. The firing of most of these neurons is deeply modulated as a function of the phase of the theta rhythm. This is true whether the theta rhythm occurs during walking or during urethane anesthesia, but for some types of cells the mean phases of firing are different in the two types of theta rhythm. During walking, pyramidal cells and interneurons in all hippocampal subregions and dentate granule cells have a maximum probability of firing near the positive peak of the theta rhythm recorded in the outer molecular layer of the dentate (dentate theta). During urethane anesthesia, the maximum firing probability for interneurons in CA1 and for dentate granule cells occurs near the negative peak of the dentate theta, while the phases of maximum firing for pyramidal cells and interneurons in CA3 and CA4 become widely distributed. The phases of maximum firing of pyramidal cells in CA1 are, if anything, more narrowly distributed around the positive peak of the dentate theta during urethane anesthesia than during walking. These differences in the firing of hippocampal cells during walking and urethane anesthesia represent some of the differences in cellular mechanisms distinguishing two kinds of hippocampal theta rhythm.     

Firing relations of lateral septal neurons to the hippocampal theta rhythm in urethane anesthetized rats

Summary The firing of lateral septal neurons was examined in relation to the hippocampal theta rhythm in urethane anesthetized rats. In general, the firing rates of these cells were low during both theta and non-theta EEG states. There was no significant change in firing rate between the two states (theta: 8.5±9.9 spks/sec; non-theta: 6.0±5.3). Sixty-four of 68 cells fired simple spikes and 4 cells were found to fire bursts of action potentials (complex-spikes). Approximately 30% (21/65) of the cells showed a significant phase relation to the hippocampal theta rhythm. The preferred phases of firing of these 21 cells were broadly distributed. The possibility that the phase-locked firing of LSN cells is due to the phase-locked firing of hippocampal projection cells is discussed.     

Developmental plasticity of ventilatory control in zebrafish, Danio rerio

To determine whether development of ventilatory control in zebrafish (Danio rerio) exhibits plasticity, embryos were exposed to hypoxia, hyperoxia or hypercapnia for the first 7 days post-fertilization. Their acute reflex breathing responses to ventilatory stimuli (hypoxia, hypercapnia and external cyanide) were assessed when they had reached maturity (3 months or older). Zebrafish reared under hyperoxic conditions exhibited significantly higher breathing frequencies at rest (283+/-27min(-1) versus 212+/-16min(-1) in control fish); breathing frequency was unaffected in adult fish subjected to hyperoxia for 7 days. The respiratory responses of fish reared in hyperoxic water to acute hypoxia, hypercapnia or external cyanide were blunted (hypoxia, cyanide) or eliminated (hypercapnia). Adult fish exposed for 7 days to hyperoxia showed no change in acute responses to these stimuli. The respiratory responses to acute hypoxia, hypercapnia or external cyanide of fish reared under hypoxic or hypercapnic conditions were similar to those in fish reared under normal conditions. A subset of all fish examined exhibited episodic breathing; an analysis of breathing patterns demonstrated that fish reared under hypercapnic conditions had an increased tendency to display episodic breathing. The results of this study reveal that there is flexibility in the design and functioning of the embryonic or larval respiratory system in zebrafish.     

Generalized vs. stimulus-specific learned fear differentially modifies stimulus encoding in primary sensory cortex of awake rats

Experience shapes both central olfactory system function and odor perception. In piriform cortex, odor experience appears critical for synthetic processing of odor mixtures, which contributes to perceptual learning and perceptual acuity, as well as contributing to memory for events and/or rewards associated with odors. Here, we examined the effect of odor fear conditioning on piriform cortical single-unit responses to the learned aversive odor, as well as its effects on similar (overlapping mixtures) in freely moving rats. We found that odor-evoked fear responses were training paradigm dependent. Simple association of a condition stimulus positive (CS+) odor with foot shock (unconditioned stimulus) led to generalized fear (cue-evoked freezing) to similar odors. However, after differential conditioning, which included trials where a CS- odor (a mixture overlapping with the CS+) was not paired with shock, freezing responses were CS+ odor specific and less generalized. Pseudoconditioning led to no odor-evoked freezing. These differential levels of stimulus control over freezing were associated with different training-induced changes in single-unit odor responses in anterior piriform cortex (aPCX). Both simple and differential conditioning induced a significant decrease in aPCX single-unit spontaneous activity compared with pretraining levels while pseudoconditioning did not. Simple conditioning enhanced mean receptive field size (breadth of tuning) of the aPCX units, while differential conditioning reduced mean receptive field size. These results suggest that generalized fear is associated with an impairment of olfactory cortical discrimination. Furthermore, changes in sensory processing are dependent on the nature of training and can predict the stimulus-controlled behavioral outcome of the training.     

MK-801, a non-competitive NMDA receptor antagonist, produces facilitation of the micturition reflex in awake, freely-moving rats.

MK-801 (dizocilpine), a non-competitive N-methyl-D-aspartate (NMDA) receptor blocker, produced a dose-dependent (30-120 micrograms/kg, i.v.) increase in the frequency of micturition (as well as the already described behavioral effects) in awake, freely-moving rats. The contraction amplitude was also slightly increased. In contrast, MK-801 administered to urethane-anesthetized rats resulted in complete inhibition of bladder contractions. The effect of MK-801 on the frequency of bladder contractions, therefore, is anesthetic dependent. Excitatory amino acids acting at NMDA receptors may play a role in the control of micturition.     

The neurobiology of language and verbal memory: observations from awake neurosurgery.

Neurosurgical operations under local anesthesia provide a unique opportunity to investigate the neurobiology of human cognition. We have studied the cortical organization of language and verbal memory in this setting, using two different techniques: electrical stimulation mapping and extracellular microelectrode recording of activity of individual neurons. The two techniques provide very different perspectives. Stimulation mapping identifies brain areas that are essential for a behavior, while changes in neuronal activity can occur in non-essential regions. Stimulation mapping identifies multiple discrete areas in perisylvian cortex of the dominant hemisphere as essential for a function, with separation of areas for different aspects of language including naming in two languages, different semantic classes, naming compared to reading, and language from verbal memory. There is substantial individual variation in the location of these essential areas, variability that in part relates to subjects age, gender and verbal abilities. Neurons changing activity with language or verbal memory are widely distributed, in both hemispheres. However, individual neurons usually change activity with only one function, including naming in only one of two languages, only naming or reading, or with recent verbal memory encoding but not identification of similar items. A few lateralized changes in neuronal activity have been identified, including a predominance of inhibition in dominant hemisphere with naming, and polymodal memory responses in dominant hemisphere, unimodal in nondominant. Specific neuronal populations have been identified that are related to different aspects of memory, that differentiate correct from incorrect identification or memory performance and differentiate learned from unlearned associations, with some evidence of differences in neuronal activity related to subjects' ability.     

Optical imaging of digit topography in individual awake and anesthetized squirrel monkeys

Topographic maps and columnar structures are fundamental to cortical sensory information processing. Most of the knowledge about detailed topographic maps and columnar structure comes mainly from experiments conducted on anesthetized animals. Towards the goal of evaluating whether topographic maps change with respect to behavioral demands, we used intrinsic signal optical imaging in alert monkeys to examine the spatial specificity of cortical topographic representation. Specifically, the somatotopies of neighboring distal finger pad representation in areas 3b and 1 were examined in the same awake and anesthetized squirrel monkey. In comparison to the anesthetized animal, we found larger cortical activation sizes in the alert animal in area 3b, where activation widths were found to overlap with even non-adjacent digits. This may suggest that in the alert animal, there is less inhibition across the somatotopic map within area 3b.     

K and Ca dependence of inspiratory-related rhythm in novel “calibrated” mouse brainstem slices

Recently developed transversal newborn rat brainstem slices with “calibrated” rostrocaudal margins unraveled novel features of rhythmogenic inspiratory active pre-Bötzinger complex (preBötC) neural networks (Ballanyi and Ruangkittisakul, 2009). For example, slice rhythm in physiological (3 mM) superfusate K⁺ is depressed by modestly raised Ca²⁺ and restored by raised K⁺. Correspondingly, we generated here calibrated preBötC slices from commonly used newborn C57BL/6 mice in which rostrocaudal extents of respiratory marker structures, e.g., the inferior olive, turned out to be smaller than in newborn rats. Slices of 400–600 μm thickness with likely centered preBötC kernel (“m-preBötC slices”) generated rhythm in 3 mM K⁺ and 1 mM Ca²⁺ for several hours although its rate decreased to <5 bursts/min after >1 h. Rhythm was stable at 8–12 bursts/min in 6–7 mM K⁺, depressed by 2 mM Ca²⁺, and restored by 9 mM K⁺. Our findings provide the basis for future structure–function analyses of the mouse preBötC, whose activity depends critically on a “Ca⁺/K⁺ antagonism” as in rats.     

I.v. cocaine induces rapid, transient excitation of striatal neurons via its action on peripheral neural elements: single-cell, iontophoretic study in awake and anesthetized rats

Cocaine's (COC) direct interaction with the dopamine (DA) transporter is usually considered the most important action underlying the psychomotor stimulant and reinforcing effects of this drug. However, some physiological, behavioral and psycho-emotional effects of COC are very rapid and brief and they remain intact during DA receptor blockade, suggesting possible involvement of peripheral non-DA neural mechanisms. To assess this issue, single-unit recording with microiontophoresis was used to examine changes in impulse activity of dorsal and ventral striatal neurons to i.v. COC (0.25-0.5 mg/kg) in the same rats under two conditions: awake with DA receptor blockade and anesthetized with urethane. In the awake preparation approximately 70% striatal neurons showed rapid and transient (latency approximately 6 s, duration approximately 15 s) COC-induced excitations. These effects were stronger in ventral than dorsal striatum. During anesthesia, these phasic effects were fully blocked and COC slowly decreased neuronal discharge rate. Cocaine-methiodide (COC-M), a derivative that cannot cross the blood-brain barrier, also caused phasic excitations in the awake, but not anesthetized condition. In contrast to regular COC, COC-M had no tonic effect on discharge rate in either preparation. Most striatal neurons that were phasically excited by both COC forms also showed short-latency excitations during tail-touch and tail-pinch in the awake preparation, an effect strongly attenuated during anesthesia. Finally, most striatal neurons that in awake conditions were phasically excited by somato-sensory stimuli and COC salts were also excited by iontophoretic glutamate (GLU). Although striatal neurons were sensitive to GLU in both preparations, the response magnitude at the same GLU current was higher in awake than anesthetized conditions. These data suggest that in awake animals i.v. COC, like somato-sensory stimuli, transiently excites striatal neurons via its action on peripheral neural elements and rapid neural transmission. While the nature of these neuronal elements needs to be clarified using other analytical techniques, they might involve voltage-gated K(+) and Na(+) channels, which have a high affinity for COC and are located on terminals of visceral sensory nerves that densely innervate peripheral vessels. Therefore, along with direct action on specific brain substrates, central excitatory effects of COC may occur via indirect action, involving afferents of visceral sensory nerves and rapid neural transmission. By providing a rapid sensory signal and triggering transient neural activation, such a peripherally triggered action might play a crucial role in the sensory effects of COC, thus contributing to learning and development of drug-taking behavior.     

Hypoxic inhibition of respiratory neural regulation in anesthetized rats.

To determine the neural mechanism of hypoxic respiratory inhibition, discharge patterns of efferent phrenic (Phr), vagal superior laryngeal (Xsl), and vagal pharyngeal (Xphar) nerves were analyzed during systemic hypoxia in the urethane-anesthetized, vagotomized and artificially ventilated rat. In the carotid sinus nerve (CSN) intact rat, moderate hypoxia (end-tidal Po2, 40-50 mmHg) caused an initial increase in respiratory activity which was followed by inhibition due to reduction in respiratory frequency (f). The decrease in f was associated with prolongation of decremental Xphar expiratory (E) activity and retardation of the onset of inspiratory (I) activity. Integrated peak Phr or Xs1 I and Xphar E activities remained augmented during respiratory inhibition. After bilateral CSN section, moderate hypoxia produced an extreme reduction in f due to delayed onset of I activity and a strong reduction in the Xphar E activity. Phr and Xs1 I activities were little affected, and changes in inspiratory time were small. These results suggest that hypoxia centrally inhibits the process of initiating the onset of rhythmic I activity and the activity of decremental Xphar E motoneurons. Carotid chemoreceptor stimulation was inadequate to offset the central inhibitory effect of hypoxia on the onset of I activity.     

Somatic afferent regulation of plasma corticosterone in anesthetized rats.

Effects of cutaneous stimulation on plasma corticosterone were examined in adult male Wistar rats anesthetized with pentobarbital. Under the resting condition, plasma corticosterone measured every 15 min between 1430 and 1630 h revealed no significant circadian fluctuations. Nociceptive mechanical stimulation of bilateral hindpaws by pinching for 10 min significantly increased plasma corticosterone for the following 1 h, whereas innocuous mechanical stimulation of bilateral hindlimbs by brushing for 10 min produced no significant change in plasma corticosterone. These results indicate that somatic sensory information from skin can influence secretion of corticosterone from the adrenal cortex after emotional factors are eliminated by anesthetizing the subjects.     

Hypoxia and hypercapnia in asphyctic differentiation of regional sympathetic activity in the anesthetized rabbit

Summary The contributions of hypoxia and of hypercapnia to the differentiated changes of regional sympathetic activity during asphyxia were investigated in anesthetized, paralyzed rabbits. Under artificial ventilation with gas mixtures of various O₂ and CO₂ contents, the discharges of a postganglionic nerve twig accompanying the retroauricular artery (cutaneous sympathetic) and of a splanchnic nerve branch (visceral sympathetic) were recorded. PaO₂, PaCO₂, pH, arterial pressure, and heart rate were measured.Moderate hypoxia (PaO₂ 27.2 Torr) induced a differentiated response of regional sympathetic activity similar to that observed during moderate asphyxia, i.e. increase of visceral and decrease of cutaneous sympathetic activity. During severe hypoxia (PaO₂ 16.4 Torr) both visceral and cutaneous sympathetic activity increased, the latter after a temporary decrease.—During hypercapnia (PaCO₂ 59.3 Torr) only a slight increase of visceral sympathetic activity was observed, while cutaneous sympathetic activity did not change.—It is concluded that the differentiated responses of the sympathetic nervous system during asphyxia are caused mainly by hypoxia.