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Biomedical subjects

A L Beckman

Publications and source records attributed to A L Beckman.

At least 19 recordsLinked to original sources
PubMed1999

Major changes in the brain histamine system of the ground squirrel Citellus lateralis during hibernation.

Hibernation in mammals such as the rodent hibernator Citellus lateralis is a physiological state in which CNS activity is endogenously maintained at a very low, but functionally responsive, level. The neurotransmitter histamine is involved in the regulation of diurnal rhythms and body temperature in nonhibernators and, therefore, could likely play an important role in maintaining the hibernating state. In this study, we show that histamine neuronal systems undergo major changes during hibernation that are consistent with such a role. Immunohistochemical mapping of histaminergic fibers in the brains of hibernating and nonhibernating golden-mantled ground squirrels (C. lateralis) showed a clear increase in fiber density during the hibernating state. The tissue levels of histamine and its first metabolite tele-methylhistamine were also elevated throughout the brain of hibernating animals, suggesting an increase in histamine turnover during hibernation, which occurs without an increase in histidine decarboxylase mRNA expression. This hibernation-related apparent augmentation of histaminergic neurotransmission was particularly evident in the hypothalamus and hippocampus, areas of importance to the control of the hibernating state, in which tele-methylhistamine levels were increased more than threefold. These changes in the histamine neuronal system differ from those reported for the metabolic pattern in other monoaminergic systems during hibernation, which generally indicate a decrease in turnover. Our results suggest that the influence of histamine neuronal systems may be important in controlling CNS activity during hibernation.

Animals↗
PubMed1995

Morphine antinociception in the non-hibernating and hibernating states of the ground squirrel (Citellus lateralis).

Previous work in our laboratory demonstrated a significant reduction in the development of morphine physical dependence during hibernation, suggesting a major change in the ability of morphine to act on the central nervous system (CNS) during this naturally altered state. To further investigate the pharmacological actions of morphine during the hibernating (H) state, the present study recorded skin-twitch response (STR) latency as a measure of morphine antinociception in the golden-mantled ground squirrel (Citellus lateralis) during the non-hibernating (NH) and H states. Our results revealed that morphine antinociception continued to develop in hibernation. Moreover, the magnitude of antinociception displayed was greater during the H state than in the NH state. Tolerance to morphine's antinociceptive effects developed in both states as well. The results of the present study indicate that the hibernation-related reduction in the development of morphine dependence represents a selective, rather than a general, suppression of the CNS pharmacological actions of morphine during the H state.

Animals↗
PubMed1995

Quantitative and qualitative aspects of the hibernation-related reduction of morphine physical dependence in the ground squirrel (Citellus lateralis).

The development of morphine physical dependence in the contrasting brain states of the nonhibernating (NH) vs. the hibernating (H) condition was measured in the ground squirrel hibernator Citellus lateralis. Morphine was infused continuously into the lateral ventricle (3.44, 6.88 and 13.75 micrograms/hr for periods of 1, 3 and 6 days) in NH and H animals, followed by measurement of the naloxone (1 mg/kg s.c.) evoked abstinence syndrome during the NH state (i.e., H animals were tested after arousal to the NH state). The results showed that morphine treatment during the NH state resulted in significant naloxone-evoked abstinence and an overall dose- and duration-related increase in the strength of the abstinence syndrome. By contrast, morphine treatment during hibernation resulted in significantly reduced abstinence compared with that observed after treatment during the NH state, with no significant morphine dose-response or duration-response trends evident. However, H-state morphine treatment did produce a dose-related reduction of hibernation bout duration. The reduction in the strength of dependence during the H state was associated with a qualitative change in the abstinence syndrome, as revealed by exploratory factor analysis. This change was reflected by an approximate reversal of the rank order of abstinence signs. These results demonstrate that hibernation-related changes in central nervous system function significantly reduce the liability for and change the character of the development of morphine dependence.

Animals↗
PubMed1993

Changes in striatal dopamine metabolism during the development of morphine physical dependence in rats: observations using in vivo microdialysis.

The present study examined the effect of prolonged morphine treatment on striatal dopamine (DA) release and metabolism, during the initial phase of the development of morphine dependence. Sprague-Dawley rats were implanted with chronic guides for microdialysis of the striatum. Morphine (two 75-mg pellets, subcutaneous implant) or placebo was given (12 hr) to pentobarbital anesthetized animals. Following recovery from anesthesia, morphine physical dependence was verified by the naloxone-evoked abstinence syndrome. Morphine produced significant increases in the dialysate level of DA nad its metabolites (DOPAC and HVA) above baseline compared to placebo treatment. HVA levels began to increase immediately following morphine administration, whereas DA and DOPAC levels began to increase after a latency of one and three hr, respectively. Morphine effects on striatal DA metabolism included changes in the metabolic disposition of DA. Increases in HVA concentration accompanied increases in DOPAC concentration up to a threshold value of DOPAC efflux; further increases in DOPAC level were associated with decreases in HVA level. These in vivo data suggest that morphine-induced changes in the regulation of striatal dopaminergic function may be an important component of the development of physical dependence.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Morphine physical dependence in the hibernator: central nervous system mechanisms underlying the development of dependence remain functional during depression induced by pentobarbital anesthesia.

Earlier work suggested that adaptive mechanisms of the hibernating brain may also block the development of morphine physical dependence. To test an alternate view that CNS depression itself might be the major factor in the failure of dependence to develop, we compared the strength of dependence produced by morphine (two 75-mg pellets, s.c.) given for 12 hr in the presence, versus in the absence, of continuous pentobarbital anesthesia in nonhibernating ground squirrels (Citellus lateralis) and, in addition, in rats. Dependence was measured by the naloxone (5 mg/kg, s.c.) evoked abstinence syndrome in the awake state. The results demonstrated that pentobarbital-induced general anesthesia does not significantly reduce the development of morphine dependence in either species. We conclude that CNS depression alone does not account for the hibernation-related reduction in morphine physical dependence.

Anesthesia↗
PubMed1992

Reduction of hibernation bout duration by intraventricular infusion of met-enkephalin.

The potential of brain met-enkephalin (met-enk) systems to modulate central nervous system (CNS) activity during periods of general depression (modeled by the mammalian hibernation state) was studied in the ground squirrel (Citellus lateralis). Following entrance into hibernation, continuous met-enk infusion into the lateral ventricle (1 microliter/h; 0.2, 1 and 5 micrograms/microliter) produced a dose-dependent reduction in bout duration ranging from 1.2 to 3.9 days (13.8-44.6% of baseline bout duration). We suggest that the activity of met-enk-releasing neurons may serve to increase the excitability of the depressed CNS, thus accelerating the termination of the hibernation bout.

Animals↗
PubMed1991

Serotonergic response to spinal distraction trauma in experimental scoliosis.

The effects of distraction injury to the spinal cord on serotonin (5HT) content and metabolism in a rat model of scoliosis were studied. Previous studies in this laboratory (Salzman et al., 1987a) have identified the 5HT response as a major component of the posttraumatic progression of spinal injury after impact trauma in the rabbit. The present study was designed to determine the universality of this response by examining a different model of injury in a different species. The results demonstrate that distraction trauma in the rat, like impact injury in the rabbit, is associated with a rapid and robust increase in the local spinal cord content and metabolism of 5HT and a long-term depletion of 5HT below the site of injury. The roles of the blood platelet and the raphe-spinal tract in the acute response and the disruption of axoplasmic transport during the chronic phase of injury are discussed.

Animals↗
PubMed1988

The somatosensory evoked potential predicts neurologic deficits and serotonergic pathochemistry after spinal distraction injury in experimental scoliosis.

The validity of the somatosensory evoked potential as an intraoperative spinal cord monitor was evaluated in an experimental model of scoliosis in the rat and a Harrington distraction model of injury. Under these conditions, it was found that any change in latency or amplitude of the major negative wave above a certain level was a significant predictor of an adverse neurologic outcome. Changes in latency of 4% or greater and changes in amplitude of 50% or greater were unequivocal indicators of spinal cord injury. Postmortem analyses of the spinal neurotransmitter serotonin revealed that apparent false-positive results of the SEP were, in fact, true-positive results.

Animals↗
PubMed1988

Experimental scoliosis in the rat. I. Methodology, anatomic features and neurologic characterization.

The purpose of this study was to develop a simple and reproducible model of scoliosis in the rat without producing direct trauma to the spine, in order to both provide a system for the study of human scoliosis and to ultimately study the conditions under which distraction-induced trauma might occur. Right lateral curvatures were produced in three groups of rats (N = 36, 59, 25) at 18-21 days of age by suturing the inferior angle of the scapula to the ipsilateral bony pelvis. In the first group of animals, it was found that a minimum period of 6 weeks of tethering was required in order to produce permanent structural curvatures after release of the tethering sutures. In the second group of rats, a number of morphologic and histologic changes characteristic of human scoliosis were noted, including apical wedging, deviation of the apical spinous process, pelvic asymmetry, rib hump deformity, vertebral rotation, displacement of the nucleus pulposus, disorganized columnization of disc cartilage cells, and an increased number of Type I muscle fibers in paravertebral muscle on the convex side of the curve. Finally, in the third group of rats, a mild spasticity was seen in the ipsilateral hindlimb in approximately one-third of the animals with curvatures greater than 40 degrees. This spasticity was not associated with a change of latency or amplitude of the somatosensory-evoked potential (SSEP). Each curvature group displayed SSEP characteristics that were not statistically different from unoperated control animals. These results indicate the validity of this model system for the study of scoliosis, and, in particular, its usefulness for the study of operative-induced trauma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Experimental scoliosis in the rat. II. Biomechanical analysis of the forces during Harrington distraction.

The purpose of this study was to characterize the forces resulting from Harrington distraction of the spine in an experimental model of scoliosis in the rat, in order to establish both the similarity of this model to human scoliosis and identify potential force parameters that may be useful for clinical decision-making. Harrington distraction was performed in 36 rats that had been made scoliotic 9-12 weeks earlier by the method described in the previous paper. Distractions were carried out in discrete and timed steps until separation of the vertebral laminae (mechanical failure) occurred at the upper hook site. Distractive forces were monitored continuously by a strain gauge mounted on the tension side of the upper arm of the outrigger. The resulting data were compared among the various curvature groups. The relationship between the length of distraction and the maximum force produced was similar for all animals regardless of curvature. This relationship was quadratic and was characterized by an inflection point where forces increased rapidly with each distraction. The amount of distraction necessary to reach both the inflection and failure points differed only for curves above 100 degrees. The amount of force required to reach failure was lower for curves above 75 degrees. Curves above 50 degrees had a lower percent correction at the inflection point. Bending and tensile forces were calculated by vector analysis. Axial load efficiencies were greater for curves above 50 degrees, as evidenced by increased bending forces in these animals. The viscoelasticity of the spine decreased after inflection in all animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Treatment of experimental spinal trauma with thyrotropin-releasing hormone: central serotonergic and vascular mechanisms of action.

The sites and mechanisms by which thyrotropin-releasing hormone (TRH) may ameliorate the effects of spinal cord contusion were studied in the rabbit. We have examined the actions of an effective intravenous TRH infusion on the spinal content and utilization of the monoamine neurotransmitters (norepinephrine [NE], dopamine [DA], and serotonin [5-HT]) in both control and injured animals. The ability of TRH to penetrate the blood-brain barrier was determined by the measurement of spinal cord TRH immunoreactivity and the effect of TRH upon the development of traumatic edema was evaluated. TRH was found to enter the spinal cord to a large extent in approximately half the animals, but to a lesser degree in the remainder. This indicates the potential for a central site of action. In this regard, TRH induced a significant increase in the metabolism or utilization of 5-HT above the injury site. This effect was not observed in control animals. Finally, TRH was able to cancel the formation of edema at the injury site. These results are correlated with previously described mechanisms and are discussed in terms of the co-existence of TRH and 5-HT in raphe-spinal neurons descending from the medulla.

Animals↗
PubMed1987

Monoaminergic responses to spinal trauma. Participation of serotonin in posttraumatic progression of neural damage.

The monoamines norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and their major metabolites were measured in the spinal cord of rabbits following laminectomy or impact injury to the thoracic cord. Samples were taken 30 minutes, 60 minutes, 4 hours, and 6 weeks after injury. Utilization ratios (metabolite/transmitter) were calculated from the data. Turnover rates for NE and DA were also calculated at 30 minutes using the alpha-methylparatyrosine method. Trauma resulted in rapid and sustained elevations in 5-HT concentration at and around the injury site. The catecholamines were depleted slightly at the injury site. Levels of 5-hydroxyindole-3-acetic acid were elevated at 30 minutes but fell to baseline by 4 hours, resulting in a decrease in the 5-HT utilization ratio. The utilization and turnover of NE was increased at the injury site, while DA function was not affected. The large short-term increase in 5-HT levels may have been due to extravasation of platelet 5-HT stores into spinal tissue, rather than due to changes in neuronal 5-HT metabolism. At 6 weeks after injury, each monoamine and metabolite appeared to accumulate in spinal cord tissue proximal to the insult. Distal to the injury, depleted amine stores displayed augmented utilization. The data are discussed in terms of a serotonergic hypothesis of the progression of neural damage after trauma, with the interaction of 5-HT with raphe-spinal nerve terminals as a principal event.

Animals↗
PubMed1986

Hippocampal and cortical opioid receptor binding: changes related to the hibernation state.

In vitro opioid receptor binding in the dorsal hippocampal formation and parietal cortex was surveyed in ground squirrels (Citellus lateralis) in the contrasting physiological states of hibernation and euthermia (i.e. not hibernating). Computer-assisted autoradiographic analysis of coronal sections incubated with [3H]dihydromorphine (DMH; 4 nM) revealed statistically significant reductions in specific opioid binding associated with hibernation. In the dorsal hippocampal formation of hibernating animals, binding in the stratum radiatum of CA3, hilus of the dentate gyrus and molecular layer of the dentate gyrus exhibited decreases up to 34% compared to euthermic animals. The stratum radiatum of CA3 exhibited the smallest decrease overall. DHM binding in parietal cortex displayed significant hibernation-related reductions, although they were not uniformly observed across all laminae at the 3 different brain levels examined. These experiments present evidence of changes in brain opioid binding related to the mammalian state of hibernation. The results suggest that changes in opioid receptor binding during hibernation may contribute to the earlier reported apparent failure of morphine physical dependence to develop during hibernation.

Animals↗
PubMed1986

Effects of halothane on intraoperative scalp-recorded somatosensory evoked potentials to posterior tibial nerve stimulation in man.

Somatosensory evoked potentials (SEPs) were monitored in 116 patients receiving halothane anesthesia during spinal fusion surgery. Whereas it has been generally assumed that the use of halogenated inhalational anesthetics should be avoided with SEP monitoring because of their purported deleterious effects on scalp-recorded sensory responses, we found that reproducible SEPs were obtained throughout the surgical procedure in 91% of the cases we monitored while using halothane at concentrations of 0.25-2.0%. In those cases in which halothane was delivered continuously at 0.5%, reproducible evoked responses were recorded in 96% (75 of 78) of the patients. Our data demonstrated 3 major effects of halothane on the SEP: (a) a small but significant decrease in the average amplitude of the first two components (N25 and P30), (b) a significant increase in the average latency of the late positive component (P53) of the wave form, and (c) occasional obliteration of components N25, N40, P53, and N71, but never of P30. These effects did not, in most cases, interfere with our ability to obtain clinically useful recordings. Our results suggest that in many instances the use of halothane anesthesia can be combined successfully with the recording of intraoperative SEPs.

Electric Stimulation↗
PubMed1986

Morphine distribution following infusion into lateral ventricle during hibernation and euthermia.

The intracerebral pattern of diffusion of 3H-morphine was studied autoradiographically following continuous infusion (4, 9, and 18 hr; 1 microliter/hr) into the lateral ventricle during hibernation and euthermia (i.e., not hibernating) in ground squirrels (Citellus lateralis). Morphine diffusion into the parenchyma during both states was extensive, resulting in increased autoradiographic optical density of 34 structures examined. The zone of radiolabeled tissue was primarily ipsilateral, and it expanded with increasing duration of infusion. Diffusion into contralateral regions was more evident in hibernation, although the total area of radiolabeled tissue was not significantly greater than that of euthermic animals. The average optical densities of autoradiographs from hibernating brains were significantly greater than those from euthermic animals, suggesting greater accumulation of labeled material during hibernation. These data suggest that neuroactive compounds released into the ventricular space can achieve widespread distribution within the brain during hibernation (in which all physiological parameters are profoundly depressed) as well as during euthermia. Thus, the apparent lack of development of physical dependence to morphine during hibernation is not due to a restricted distribution of morphine in the hibernating brain.

Animals↗
PubMed1985

Changes in body temperature and metabolic rate following microinjection of Met-enkephalinamide in the preoptic/anterior hypothalamus of rats.

The effects of Met-enkephalinamide (MET-ENKamide) on brain temperature (Tb) and metabolic rate (MR) were assessed following direct administration into the preoptic/anterior hypothalamus (PO/AH) of freely moving rats. Bilateral microinjections of saline or MET-ENKamide (1-25 micrograms/microliter) were delivered through cannula guide tubes previously implanted in nine animals. Thiorphan, an enkephalinase inhibitor, was microinjected into the PO/AH of two of the animals. All injections were made remotely at an ambient temperature of 22 +/- 1 degree C in a volume of 1 microliter. Measurements of Tb (via a brain-dwelling thermistor) and MR were recorded continuously. The ability of naloxone to antagonize the effects of MET-ENKamide was investigated by fashioning a double-barreled injection cannula to fit within each guide tube; 1 microliter of saline or naloxone (1-10 micrograms) was delivered bilaterally into the PO/AH followed by 1 microliter of MET-ENKamide (25 micrograms) 5-10 min later. PO/AH administration of MET-ENKamide (1-25 micrograms) produced dose-dependent increases in Tb preceded by dose-dependent increases in MR, with a characteristic time course of approximately 30 min. Naloxone antagonized the rise in Tb and MR, either partially or completely, depending on dose. When administered alone, naloxone had no effect on Tb or MR. Microinjection of thiorphan (10 micrograms) into the PO/AH evoked increases in Tb and MR that were similar to those responses induced by MET-ENKamide. These results support a role for endogenous Met-enkephalin in the regulation of Tb in the rat.

Animals↗
PubMed1985

Determination of intraoperative plasma catecholamine concentrations using liquid chromatography with electrochemical detection.

Liquid chromatography with electrochemical detection was used for the determination of norepinephrine and epinephrine in human plasma samples obtained prior to, after, and six times during the course of spinal fusion surgery for the correction of scoliosis. The catecholamines were extracted from plasma by alumina adsorption and chromatographed isocratically using a reversed-phase, ion-pairing system. Data obtained are compared to those obtained intraoperatively by other authors using a radioenzymatic method, and the mechanism of sympathetic activation during surgery is discussed. Preliminary data using 3-micron particle size columns and dual-parallel electrochemical detection are presented.

Adolescent↗