Charles D. Barnes

Facilitation of the lumbar monosynaptic reflexes by locus coeruleus stimulation

Abstract A conditioning train of stimuli delivered in the vicinity of the locus coeruleus elicited a marked (average 104%) facilitation of the lumbar monosynaptic reflex in decerebrated cats. Placement of the electrode in periaqueductal gray resulted in a biphasic facilitatory action in the MSR. Phenoxybenzamine (2 mg/kg) and chlorpromazine (1–2 mg/kg) caused marked reductions in LC-induced augmentations. Haloperidol appeared to potentiate LC-elicited facilitation. These data further verify the noradrenergic nature of fibers originating from the locus coeruleus and assign a physiological role to coeruleo-spinal projection in the regulation of lumbar MSR.

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.

Bilateral lesions of the fastigial nucleus prevent the recovery of blood pressure following hypotension induced by hemorrhage or administration of endotoxin

The present studies were undertaken to determine if bilateral lesions of the fastigial nuclei of the cerebellum would impair the recovery and maintenance of mean arterial blood pressure during hypotension caused by hemorrhage or administration of endotoxin. We had shown previously that cerebellectomy would produce such an impairment, and the fastigial nuclei were implicated as the specific area involved due to the known pressor response observed when they are stimulated electrically. Chloralose-anesthetized dogs were made hypotensive by administration of E. coli endotoxin or hemorrhage to 50 mm Hg and observed over the subsequent 3 h. Dogs with fastigial nucleus lesions had a significantly lower mean arterial pressure during both the recovery and maintenance phases when compared with intact animals under both hypotensive protocols. In the hemorrhage study, a significant number of lesioned animals died whereas none of the controls died. Lesion of the fastigial nuclei produced an impairment similar to that seen with cerebellectomy. It is concluded that the fastigial nuclei play an important role in the recovery of blood pressure following a hypotensive episode.

Inhibitory effects of substantia nigra on impulse transmission from nociceptors

&NA; In precollicularly decerebrated cats immobilized with Flaxedil (2 mg/kg, i.v.), a dopamine mechanism played a role in the inhibition produced by brain stem stimulation of nociceptive activated cells in the spinal cord. Lamina V cell activity evoked by natural stimulation (pinch not touch) to the left hind limb or electrical stimulation (0.1 msec pulses at 1/sec) to the left sural nerve exposed at the popliteal fossa was recorded at levels L6 and L7. Brain stimulation consisted of 100 msec trains of either single rectangular pulses or 3 pulses/sec for 1 min. The stimulation was delivered to substantia nigra, periaqueductal gray (PAG) and dorsal raphe nucleus via concentric bipolar electrodes. Descending inhibition of the late burst of lamina V cell discharge elicited by mechanical pinch or sural shock could be demonstrated following individual stimulation of the 3 brain stem sites. Nigral‐induced inhibition was abolished by injecting tetrabenazine (40 mg/kg, i.v.) or bulbocapnine (20 mg/kg, i.v.); the inhibition was re‐established by L‐DOPA (20 mg/kg, i.v.) or apomorphine (20 mg/kg, i.v.) indicating that a dopaminergic link has access to the descending inhibitory action on segmental transmission of “pain” impulses. Both nigral and PAG actions were sensitive to methysergide (1 mg/kg, i.v.), while the serotonergic blockade could be overcome by 5‐hydroxytryptamine (70 mg/kg, i.v.). We proposed that nigral and PAG actions were relayed in part through the descending raphe system. Through this relay, they exhibit their antinociceptive effects.

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.

Brainstem noradrenergic system depression by cyclobenzaprine.

Abstract A possible mechanism for CBZs depressant action on the brainstem noradrenergic system was investigated in precollicularly decerebrated cats immobilized with Flaxedil (2 mg/kg, i.V.). Phenoxybenzamine (2 mg/kg, i.v.) was consistently observed to antagonize CBZs suppression of both the flexor and extensor MSRs. Subsequent evidence for the brainstem noradrenergic system mediating the CBZ effect was established by extracellular recordings. Unitary discharges of LC neurons identified histologically were demonstrated to be inhibited chiefly by CBZ (1 mg/kg, i.V.). In some instances, the inhibition of spontaneous coerulear activity was found to parallel temporally the MSR response following CBZ administration. Coerulospinal neurons characterized by physiological criteria also revealed diminished activities following CBZ (0.5 mg/kg, i.V.). A decreased neuronal somatic excitability was also observed by the antidromically driven coerulospinal neurons following CBZ. It is concluded that CBZs depressant action is mediated, at least in part, by the noradrenergic coerulospinal system. Other possible mechanisms of CBZ action are also discussed.

Inhibition of Periaqueductal Gray Neurons by the Arcuate Nucleus: Partial Mediation by an Endorphin Pathway*

SummaryElectrical activation of the ipsilateral arcuate region of the hypothalamus produced an inhibitory influence upon three separate subpopulations of cells encountered in the ventrolateral PAG. Quiescent PAG cells were classified by their response pattern to sural nerve stimulation: Type A cells displayed only a short latency discharge; whereas, Type B cells exhibited a triphasic response pattern. Arcuate nucleus stimulation dramatically reduced the evoked discharge of both A and B cell types. Type C cells represented spontaneously active PAG neurons which were less affected by arcuate nucleus activation. Systemic naloxone (5 mg/kg) reduced the degree of inhibition of only Type B neurons. Naloxone was ineffective in attenuating arcuate inhibition of Type A and C neurons. Type B neurons may represent a class of cells which are more involved in nociceptive systems and therefore are susceptible to modulation by endogenous opiate peptides.

Release of function in the spinal cord

1. Decerebration 1.

Effects of cyclobenzaprine on brainstem motor systems

Abstract Cyclobenzaprine, a new centrally acting skeletal muscle relaxant, was compared with diazepam as to their effects on several brainstem motor systems. Precollicular decerebrate cats were used to investigate intervestibular, vestibulo-spinal and reticulo-spinal effects. Both cyclobenzaprine and diazepam were without significant effect at less than high doses on the vestibular system as assessed by the monosynaptic response recorded in the median longitudinal fasciculus to vestibular nerve stimulation. The effects on brainstem reticular formation was assessed by the vestibulo-reticulo-spinal, spinal-bulbo-spinal and reticulo-spinal responses. In every case cyclobenzaprine had a strong blocking effect on reticular-produced inhibition of the spinal cord monosynaptic reflex. Diazepam was without effect or enhanced the inhibition. The evidence supports the notion that cyclobenzaprine depresses spinal cord interneurone activity by disfacilitation from a reticulo-spinal pathway.

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 Parkinsons disease; akinesia with increased tone, and the mirror effects in Huntingtons 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.