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Biomedical subjects

C D Barnes

Publications and source records attributed to C D Barnes.

At least 73 records · Page 4Linked to original sources

Control of substantia nigra pars reticulata neurons by the nucleus accumbens.

In alpha-chloralose anesthetized, immobilized and ventilated cats stimulation of the nucleus accumbens (NA) evokes either inhibition or brief excitation followed by inhibition of extracellularly recorded spontaneously active or sural driven units in substantia nigra pars reticulata (SNpr). Inhibition peaked 50-80 msec following the onset of NA stimulation and persisted for about 300 msec. Pharmacologic interventions designed to characterize this inhibition were performed. Bicuculline, 0.01 to 0.1 mg/kg IV, consistently antagonized NA elicited suppression of SNpr cells. Diazepam 0.5 mg/kg effectively reversed bicuculline actions. Inhibition of spontaneously active units as well as sural excited units was blocked by bicuculline. Strychnine 0.1 to 0.5 mg/kg IV failed to affect inhibition arising from NA. These data suggest that, analogous to the GABAergic striatonigral pathway, inhibition of SNpr cells arising from NA utilizes GABA as a transmitter.

Animals↗

The basal ganglia in extrapyramidal dysfunction.

The rapid advances in knowledge of basal ganglia circuitry and function in recent years have allowed the construction of a functional scheme to explain many facets of known pathologic states. The dichotomy of Parkinson's disease; akinesia with increased tone, and the mirror effects in Huntington's disease; hemiballismus and tardive dyskinesia, hyperkinesia with decreased tone are explained as due to two outputs of the system with an intervening inhibitory neuron which reverses the sign. The two outputs control different motor functions; pallidothalamic involved primarily with movements and nigrobrainstem involved primarily with muscle tone.

Basal Ganglia↗

The effects of chronic administration of naltrexone on appetite and water exchange in rats.

The effects of chronic administration of naltrexone (200 microgram/kg/hr) on appetitive behaviors and renal water and electrolyte excretions were studied in rats. Naltrexone reduced food and water intake, the renal excretions of water and electrolyte excretions were studied in rats. Naltrexone reduced food and water intake, the renal excretions of water and electrolytes, and osmolar clearance. No changes in plasma levels of electrolytes, plasma and urine Na+-K+ ratios, hematocrit ratio, plasma osmolality, the clearances of K+ and Na+, and the reabsorption of solute free water were found. The changes in appetite were compensated for by appropriate changes in renal excretions, resulting in no change in electrolyte balance or water exchange. These observations are discussed in relation to current theories of the role of endorphins in appetite control.

Animals↗

Interactions between femoral venous afferents and lumbar spinal reflex pathways.

This study reports findings of spinal reflex connections of afferent fibers electrically excited in the wall of the femoral vein. Condition-test experiments, and EMG recordings revealed that the femoral venous afferents have facilitatory connections to flexor and extensor motoneurons of both the proximal and the distal hindlimb muscles. Femoral venous afferent stimulation which produced facilitation, also produced inhibition of the test reflexes following the facilitation. Because the inhibition was enhanced by diazepam injection and because the inhibitory time-course correlated closely to the time-courses of both dorsal root potentials and individual tests of primary afferent depolarization, the inhibition was suggested to be produced by presynaptic inhibition. The potentially significant role of the venous afferent connections in a reflex-elicited skeletal muscle pump or in an increase in intramuscular venous counterpressure is discussed.

Afferent Pathways↗

Evidence of facilitatory coerulospinal action in lumbar motoneurons of cats.

Functional connectivity of the feline coerulospinal projection was delineated by utilizing the combined approaches of antidromic activation and electrical stimulation. We isolated 25 locus coeruleus (LC) neurons that were electrophysiologically identified and histologically verified and that could be driven by stimulating the spinal cord. Antidromicity of the spike potentials was confirmed by the constant latency, the high frequency (100 Hz) following, fractionation of the initial segment-somatodendritic potential, and collision between the antidromic and the spontaneous orthodromic spikes. The mean conduction speed was 20 +/- 8 m/sec (range = 7 to 32 m/sec). Intracellular studies revealed facilitatory LC actions in 22 lumbar motoneurons (MNs), In 13 MNs, LC activation alone produced slow-rising excitatory postsynaptic potentials (EPSPs) of 3 +/- 12 mV amplitude that lasted 4-30 msec. Six of the 13 MNs discharged action potentials upon LC stimulation. In the remaining 9 MNs, no observable potential change was registered after LC activation. Antecedent LC stimulation consistently potentiated the synaptic efficacy of testing dorsal root shocks. The enhancement of synaptic activation was antagonized by systemic injection of phenoxy-benzamine (3 mg/kg). These results suggest that facilitation of MNs by the LC is at least in part mediated by distal dendritic depolarization. Those MNs that exhibited augmented excitability but no demonstrable EPSPs may have been activated by norepinephrine-mediated synaptic modulation.

Afferent Pathways↗

Alterations in norepinephrine and dopamine content in selected brain areas of guinea pigs adapted to simulated high altitude.

The alterations in brain content of norepinephrine (NE) and dopamine (DA) were studied in guinea pigs adapted to simulated high altitude (hypobaric hypoxia) equivalent to 5500 meters. The animals were adapted for 46 days over a period of 82 days to a pressure of 375 mm Hg. The animals were then killed and the following brain parts dissected: cerebellum, neocortex, caudate head/basal forebrain, diencephalon/rhinencephalon, and brain stem. NE and DA content were analyzed by high pressure liquid chromatography with electrochemical detection by a technique described. Results showed a significant increase of NE and DA in neocortex; a significant increase of DA but not NE in caudate/basal forebrain, and a significant decrease of NE and not DA in diencephalon/rhinencephalon.

Acclimatization↗

An observed pressor effect of the cerebellum during endotoxin shock in the dog.

The current study investigates the possibility that the cerebellum may be involved in the regulation of mean arterial pressure (MAP) during endotoxin shock in the anesthetized dog. The effect of intravenously injected Escherichia coli endotoxin on MAP in the cerebellectomized dog was compared to that observed in the intact animal. Even though removal of the cerebellum did not significantly affect MAP in a control group, the cerebellectomized animal (unlike the intact animal) was unable to recover from the initial hypotension typically seen immediately following an intravenous endotoxin injection. Previous investigators have demonstrated that stimulation of fastigial nuclei in the cerebellum increases MAP via beta-adrenergic activation of the renin-angiotensin system. Captopril (SQ 14,225, an angiotensin I-converting enzyme inhibitor) was used to determine whether this system could be responsible for the maintenance of MAP during endotoxin shock. When continuously infused into the intact dog given endotoxin, captopril suppressed MAP to a level similar to that of the cerebellectomized group. A similar response pattern to endotoxin was also observed in animals with a spinal transection at C2.

Animals↗

Alterations in responses to drugs of atria from white rats acclimated to hypobaric hypoxia.

To test the hypothesis that acclimation to simulated high altitude (SHA) may occur in the tissues as well as in the systemic regulatory apparatus of an organism, atria isolated from young rats acclimated to SHA of 6,000 m and from control rats were observed under normoxic conditions. SHA atria have slower spontaneous heart rates than atria isolated from controls (209 +/- 4 vs. 228 +/- 3, P less than 0.001). SHA atria are more sensitive to pentobarbital sodium (P less than 0.001) and ethanol (P less than 0.06): spontaneous mechanical activity stops at a lower drug concentration in SHA than in control atria. SHA atria are less sensitive to norepinephrine in the concentration range of 7.9 X 10(-9) to 3.1 X 10(-6) M and respond to increased bath concentrations (3.8, 5.8 and 7.8 mM) of calcium with a significantly (P less than 0.04) smaller chronotropic response and a greater inotropic response than atria from control animals. These data support the above-mentioned hypothesis.

Acclimatization↗

Stimulation of hypothalamic arcuate nucleus inhibits locus coeruleus unit activity: evidence for endorphin mediation.

We have investigated the effect of arcuate nucleus stimulation on locus coeruleus unit activity. Extracellular LC unit activity was recorded in anesthetized cats and rats. Brief conditioning trains (25-300 microA, three shocks, 100 Hz) delivered to the arcuate nucleus produced profound inhibition (average 1000 msec, n = 30) of spontaneous coerulear cell discharges. Intravenously administered naloxone (2.5-5.0 mg/kg) or iontophoretically applied naloxone eliminated arcuate-elicited inhibition. Additionally, naloxone often increased spontaneous cell activity. In contrast to naloxone, systemically administered morphine inhibited spontaneous LC unit activity in a dose-related fashion and augmented the hypothalamic-derived inhibition. Naloxone, 5 mg/,g, reversed morphine activity to beyond predrug levels. To characterized the stereospecificity of the response, dextrorphan was administered. This inactive enantiomer failed to mimic morphine actions on LC cells. The results suggest that LC may be influenced by the beta-endorphine system originating from the arcuate nucleus.

Action Potentials↗

Effects of chronic administration of naltrexone on appetitive behaviors of rats.

Opioid antagonists have been reported to reduce water and food intake. In the experiments, ingestive behavior was sometimes induced using stressful stimuli. These experiments were conducted to determine the effects of chronic administration of an opioid antagonist on appetitive behaviors of minimally stressed rats. Twelve 4-week old rats were randomly separated into two equal-sized groups, anesthetized with ether, and implanted subcutaneously with poly(epsilon-caprolactone) capsules. One group received naltrexone in the capsules, the other group received vehicle. These capsules released the drug at a rate of approximately 250 microgram/day for over 8 weeks. Gross metabolic behavior (food intake, water intake, urine output, fecal output, and body weight) was monitored for 8 weeks. At three times during the 8 weeks, food deprivation (24 hr)-induced feeding was tested over a period of 60 min. At the end of the eighth week, the animals were subjected to an analgesic test in order to confirm the efficacy of the naltrexone dose. No differences in food intake, body weight, fecal output, or deprivation-induced feeding were observed between the control and naltrexone groups. Water intake and fluid output of the naltrexone group were significantly reduced compared to the control group. These results suggest that endogenous opioids may mediate mechanisms of tonic drinking behavior and cannot be explained as representing effects on stress-induced ingestion.

Analgesia↗

Comparative aspects of raphé-induced modulation of evoked and spontaneous cerebellar unit activity.

Electrical activation of the raphé complex predominantly inhibits spontaneous firing of randomly encountered Purkinje cells. These experiments were performed to compare the effects of raphé stimulation upon spontaneous and evoked climbing and mossy fiber inputs, as well as GABA-mediated inhibition of Purkinje cells. The findings revealed a preferential inhibitory influence of the raph nuclei on evoked simple and complex activity rather than spontaneous firing of Purkinje cells. Furthermore, the raphé appears to augment GABAergic "off-beam" inhibition of Purkinje cells.

Action Potentials↗

Motoneuron membrane changes associated with spinal shock and the Schiff-Sherrington phenomenon.

Following transection of the thoracic spinal cord, in a decerebrate cat, the forelimbs exhibit an enhanced extensor stretch reflex while the ipsilateral flexion reflex is more difficult to elicit (Schiff-Sherrington Phenomenon). The hindlimbs on the other hand have an increased threshold for the extensor stretch reflex while flexion reflexes are hyperactive (spinal shock). This investigation was designed to examine the synaptic events mediating the Schiff-Sherrington Phenomenon (SSP) and spinal shock; and to characterize any differences in the response of flexor and extensors alpha-motoneurons. This was accomplished by measuring membrane potential and input resistance of identified forelimb and hindlimb alpha-motoneurons before, during, and after coldblock of the low thoracic cord. During post-brachial spinal cord coldblock, forelimb extensor motoneurons depolarized while flexor motoneurons hyperpolarized. Both flexor and extensor motoneurons in the lumbar cord hyperpolarized. These observations account at least in part for the behavioral manifestation of increased extensor tone seen during the SSP and for the reflex depression seen during spinal shock. The membrane potential changes observed in this study were mediated through a direct effect on alpha-motoneurons since these animals were flaxedilized and gamma loop activity was probably negligible. The hyperpolarization of hindlimb motoneurons was apparently due to the removal of descending facilitation, while the depolarization seen in forelimb extensor motoneurons appeared to be due to a release of facilitation. The mechanism of the hyperpolarization observed in some forelimb motoneurons was unclear.

Animals↗