Biomedical subjects

M Marsala

Publications and source records attributed to M Marsala.

At least 37 records · Page 2Linked to original sources

PubMed1999

Localization of NADPHd-exhibiting neurons in the spinal cord of the rabbit.

Segmental and laminar distributions of nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)-exhibiting neurons were examined in the rabbit spinal cord by using horizontal, sagittal, and transverse sections. A large number of NADPHd-positive neurons in the spinal cord of rabbit appeared to fall into six categories (N1-N6), but others could not be classified. Major cell groups of NADPHd-exhibiting neurons were identified in the superficial dorsal horn and around the central canal at all spinal levels and in the intermediolateral cell column at thoracic and upper lumbar levels. NADPHd-exhibiting neurons of the pericentral region were divided into a thin subependymal cell column containing longitudinally arranged, small bipolar neurons with processes penetrating deeply into the intermediolateral cell column and/or running rostrocaudally in the subependymal layer. The second pericentral cell column located more laterally in lamina X contains large, intensely stained NADPHd-exhibiting neurons with long dendrites radiating in the transverse plane. In the pericentral region (lamina X), close association of NADPHd-exhibiting somata and fibers and mostly longitudinally oriented blood vessels were detected. Neurons of the sacral parasympathetic nucleus, seen in segments S1-S3, exhibited prominent NADPHd cellular staining accompanied by heavily stained fibers extending from Lissauer's tract through lamina I along the lateral edge of the dorsal horn to lamina V. A massive dorsal gray commissure, highly positive in NADPHd staining, was found in segments S1-S3. Scattered positive cells were also found in the deeper dorsal horn, ventral horn, and white matter. Fiberlike NADPHd staining was found in the superficial dorsal horn and pericentral region in all the segments studied. Dense, punctate, nonsomatic NADPHd staining was detected in the superficial dorsal horn, in the pericentral region all along the rostrocaudal axis, and in the nucleus phrenicus (segments C4-C5), nucleus dorsalis (segments Th2-L2), Onuf's nucleus (segments S1-S3), and the dorsal part of the dorsal gray commissure (S1-S3).

Animals↗

PubMed1999

Intrathecal substance P-induced thermal hyperalgesia and spinal release of prostaglandin E2 and amino acids.

Substance P is an important neuromediator in spinal synaptic transmission, particularly in processing nociceptive afferent information. The effects of substance P are mediated by activation of the neurokinin 1 receptor. Evidence has suggested that excitatory amino acids such as glutamate, and prostaglandins including prostaglandin E2 are involved in the enhanced spinal excitability and hyperalgesia produced by spinal substance P. In the present study, we have demonstrated that intrathecal injection of substance P (20 nmol) in rats chronically implanted with intrathecal dialysis catheters induced a decrease in thermal paw withdrawal latency (before: 10.4+/-0.3 s; after 7.6+/-0.6 s), which was accompanied by an increase in prostaglandin E2 (362+/-37% of baseline), glutamate (267+/-84%) and taurine (279+/-57%), but not glycine, glutamine, serine or asparagine. Intrathecal injection of artificial cerebrospinal fluid had no effect upon the behavior or release. Substance P-induced thermal hyperalgesia and prostaglandin E2 release were significantly attenuated by a selective neurokinin 1 receptor antagonist RP67580, but not by an enantiomer RP68651. However, substance P-induced release of glutamate and taurine was not reduced by treatment with RP67580. SR140333, another neurokinin 1 receptor antagonist, displayed the same effects as RP67580 (i.e. block of thermal hyperalgesia and prostaglandin E2 release, but not release of amino acids). These results provide direct evidence suggesting that the spinal substance P-induced thermal hyperalgesia is mediated by an increase in spinal prostaglandin E2 via activation of the neurokinin 1 receptor. These findings define an important linkage between small afferents, sensory neurotransmitter release and spinal prostanoids in the cascade of spinally-mediated hyperalgesia. The evoked release of glutamate is apparently not a result of activation of neurokinin 1 receptors. Accordingly, consistent with other pharmacological data, acute spinal glutamate release does not contribute to the hyperalgesia induced by activation of spinal neurokinin 1 receptors.

Amino Acids↗

PubMed1999

Segmental and laminar distributions of nicotinamide adenine dinucleotide phosphate-diaphorase-expressing and neuronal nitric oxide synthase-immunoreactive neurons versus radioassay detection of catalytic nitric oxide synthase activity in the rabbit spinal cord.

The distributions of neuronal nitric oxide synthase-immunoreactive neurons and of nicotinamide adenine dinucleotide phosphate-diaphorase activity were studied in the C6, Th2, L1, L5, S2 and S3 segments and laminae in the rabbit spinal cord and compared with the catalytic nitric oxide synthase activity, determined by monitoring the conversion of [3H]arginine to [3H]citrulline in the same segments and laminae. Morphologically, a heterogeneous population of nicotinamide adenine dinucleotide phosphate-diaphorase-expressing and neuronal nitric oxide synthase-immunoreactive neurons was detected in the superficial and deep dorsal horn and the pericentral region in all segments studied, and in the intermediolateral cell column of the thoracic and lumbosacral segments. A disproportionate distribution of both neuronal categories which had a significantly higher number of nicotinamide adenine dinucleotide phosphate-diaphorase-expressing rather than neuronal nitric oxide synthase-immunoreactive cell bodies was found in all segments. The catalytic nitric oxide synthase activity was distributed unequally in the C6, Th2, L1, L5, S2 and S3 segments, with a comparatively low value in the Th2 segment (70 +/- 5.1 d.p.m./microg protein) in comparison with the S3 segment, where the highest level (140 +/- 5.5 d.p.m./microg protein) was found. A close correlation between the number of neuronal nitric oxide synthase-immunoreactive somata and catalytic nitric oxide synthase activity was revealed in the dorsal horn (laminae I-VI). Whereas a low number of neuronal nitric oxide synthase-immunoreactive somata in laminae VII-X was found in the L5, S2 and S3 segments, the values of catalytic nitric oxide synthase activity in the same laminae and segments were found to be exceedingly high. These findings indicate that the occurrence of many neuronal nitric oxide synthase-immunoreactive fibers (mainly axons), and dense, punctate, non-somatic neuronal nitric oxide synthase immunopositivity in the neuropil staining of the same laminae and segments, can substantially enhance catalytic nitric oxide synthase activity.

Animals↗

PubMed1999

Hypothermia prevents biphasic glutamate release and corresponding neuronal degeneration after transient spinal cord ischemia in the rat.

1. Spinal cord ischemia evoked a biphasic increase in CSF-Glu during 20 min of ischemia (40%) and at 2 hr after reperfusion (70%) in the nontreated group that was attenuated by all treated groups. But MK-801 (15 micrograms i.t.) did not affect the increased Glu at 2 hr (80%). 2. The argyrophilia observed in laminae II-V at 8 hr after reperfusion was attenuated by hypothermia (33 degrees C) and combination with MK-801, but the attenuation was less with MK-801. 3. Mild hypothermia attenuated the biphasic increase in CSF-Glu and corresponding development of neuronal damage after spinal cord ischemia. 4. Mild hypothermia with NMDA antagonism did not yield any further effects, suggesting that hypothermia itself plays a pivotal role in the protection.

Animals↗

PubMed1999

The effect of graded postischemic spinal cord hypothermia on neurological outcome and histopathology after transient spinal ischemia in rat.

BACKGROUND: Previous data have shown that postischemic brain hypothermia is protective. The authors evaluated the effect of postischemic spinal hypothermia on neurologic function and spinal histopathologic indices after aortic occlusion in the rat. METHODS: Spinal ischemia was induced by aortic occlusion lasting 10 min. After ischemia, spinal hypothermia was induced using a subcutaneous heat exchanger. Three studies were conducted. In the first study, the intrathecal temperature was decreased to 34, 30, or 27 degrees C for 2 h beginning with initial reperfusion. In the second study, hypothermia (target intrathecal temperature 27 degrees C) was initiated with reflow and maintained for 15 or 120 min. In the third study, the intrathecal temperature was decreased to 27 degrees C for 2 h starting 5, 60, or 120 min after normothermic reperfusion. Animals survived for 2 or 3 days, at which time they were examined and perfusion fixed with 4% paraformaldehyde. RESULTS: Normothermic ischemia followed by normothermic reflow resulted in spastic paraplegia and spinal neuronal degeneration. Immediate postischemic hypothermia (27 degrees C for 2 h) resulted in decreasing motor dysfunction. Incomplete protection was noted at 34 degrees C. Fifteen minutes of immediate cooling (27 degrees C) also provided significant protection. Delay of onset of post-reflow hypothermia (27 degrees C) by 5 min or more failed to provide protection. Histopathologic analysis revealed temperature-dependent suppression of spinal neurodegeneration, with no effect of delayed cooling. CONCLUSIONS: These findings indicate that the immediate period of reperfusion (0-15 min) represents a critical period that ultimately defines the degree of spinal neuronal degeneration. Hypothermia, when initiated during this period, showed significant protection, with the highest efficacy observed at 27 degrees C.

Animals↗

PubMed1999

[Gradual postischemic reoxygenation as protection against spinal cord ischemia in an experiment].

The authors attempted reperfusion on the experimental model of spinal ischemia described most frequently in the literature. After double ligature of the aorta--closely beneath the insertion of the subclavian artery and closely above the diaphragm they induced for a period of 40 minutes a state similar to surgery of aneurysms of the thoracoabdominal part of the aorta. in 8 dogs of the control group 7 animals developed paraplegia. In the group with graded postischaemic reoxygenation induced by a change of the ventilation ratio of N2O:O2 none of the dogs was paralyzed after two days survival. The neurological condition evaluated according to Tarlov's score was consistent with the histological finding in the preparations of the spinal cord stained according to Naut. Degenerative changes of interneurons were found mainly in the control group. In the group with graded reoxygenation they were rare. This method confirmed the importance of the reperfusion stage for postischaemic damage of the spinal cord.

Animals↗

PubMed1999

[Epidural regional hypothermia for prevention of paraplegia in experimental aortic clamping].

In experiments on dogs the authors tried to elaborate methods of protection of the spinal cord from ischaemia during surgery of an aneurysm in the thoracolumbal portion of the aorta. They used the model described in the literature with double ligature of the aorta closely below the insertion of the left-sided subclavian artery and closely above the diaphragm for a period fo 40 minutes. In the control group of 8 dogs they observed severe neurological deficiency manifested by paraplegia in 7 animals. In the second group of 8 dogs the authors used local hypothermia of the spinal cord. Hypothermia was produced by epidural administration of 5 degrees C saline which they started to administer five minutes before clamping and continued throughout the period of ischaemia. The temperature of the spinal cord dropped to 26.8 degrees C. In this group none of the dogs developed neurological damage. The results were evaluated by recording spinal somatosensory potentials, by monitoring the neurological condition according to Tarlov and by histological examination of the spinal cord. In the conclusion they emphasize that this method can protect the spinal cord from 40-minute ischaemia.

Animals↗

PubMed1998

The hydroxyl radical scavenger Nicaraven inhibits glutamate release after spinal injury in rats.

Neuronal degeneration after trauma is mediated in part by release of excitatory amino acids (EAAs) and oxygen free radicals (OFR). We evaluated the effect of i.v. treatment with a hydroxyl radical scavenger ((+/-)-N,N'-propylenedinicotinamide; AVS) and spinal hypothermia (33 degrees C) on spinal CSF glutamate release after spinal trauma. In a control group, spinal compression evoked at 10 min a significant increase (5-fold) in glutamate which declined over 4 h (2.1-fold). AVS treatment attenuated glutamate release but had no additive effect. These data suggest that this compound can be effective in modulating spinal excitotoxicity resulting from increased OFR synthesis and corresponding potentiation of EAA release.

Animals↗

PubMed1998

Neurodegeneration induced by reversed microdialysis of NMDA; a quantitative model for excitotoxicity in vivo.

This study characterizes a quantifiable in vivo model of excitotoxicity. In halothane anesthetized rats, microdialysis probe was implanted into somatosensory cortex/striatum and perfused by various concentrations (1, 10, 50 and 100 mmol/l) of N-methyl-d-aspartate (NMDA) for 20 min. After 24 h, histological quantification confirmed that NMDA produced a concentration-dependent excitotoxic lesion. With 10 mmol/l NMDA, coadministration of magnesium reduced significantly, and 2-amino-5-phosphonovalerate blocked completely the development of excitotoxic injury.

2-Amino-5-phosphonovalerate↗

PubMed1998

Reduced nicotinamide adenine dinucleotide phosphate diaphorase in the spinal cord of dogs.

The distribution of somatic, fibre-like and punctate, non-somatic reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity was examined in dog spinal cord using horizontal, sagittal and transverse sections. The morphological features of NADPH diaphorase exhibiting neurons divided into six different neuronal types (N1-N6) were described and their laminar distribution specified. Major cell groups were identified in the superficial dorsal horn and around the central canal at all spinal levels, and in the intermediolateral cell column at thoracic level. NADPH diaphorase exhibiting neurons of the pericentral region were distributed in a thin subependymal cell column containing longitudinally-arranged small bipolar neurons with processes penetrating deeply into the intermediolateral cell column and/or running rostrocaudally in the subependymal layer. The second pericentral cell column located more laterally in lamina X contains large, intensely-stained NADPH diaphorase exhibiting neurons with long dendrites radiating in the transverse plane. Neurons of the sacral parasympathetic nucleus seen in segments S1-S3 exhibited prominent NADPH diaphorase activity accompanied by heavily-stained fibres extending from Lissauer's tract through lamina I along the lateral edge of the dorsal horn to lamina V. A massive dorsal gray commissure, with high NADPH diaphorase activity, was found in segments S1-S3. At the same segmental level a prominent group of moderately-stained motoneurons was detected in the dorsolateral portion of the anterior horn. Fibre-like NADPH diaphorase activity was found in the superficial dorsal horn and pericentral region in all segments studied. Punctate, non-somatic NADPH diaphorase activity was detected in the superficial dorsal horn, in the pericentral region all along the rostrocaudal axis and in the nucleus phrenicus (segments C4-C5), nucleus dorsalis (segments Th2-L2), nucleus Y (segments S1-S3), and the dorsal part of the dorsal gray commissure (S1-S3). A schematic diagram documenting the segmental and laminar distribution of NADPH diaphorase activity is given.

Animals↗

PubMed1998

Spinal neurokinin NK1 receptor down-regulation and antinociception: effects of spinal NK1 receptor antisense oligonucleotides and NK1 receptor occupancy.

To define the effects of antisense oligonucleotides on spinal neurokinin 1 (NK1) receptor function in nociceptive processing, several antisense oligonucleotides directed against the NK1 receptor mRNA were intrathecally injected into rats via an implanted catheter, and their effect on the behavioural response to formalin injected into the paw was assessed. We observed that there was no significant reduction of pain behaviour or immunostaining of spinal NK1 receptors after repeated daily intrathecal treatment with an antisense oligonucleotide. However, spinal application of substance P (SP) in the antisense oligonucleotide-treated animals resulted in a profound and long-lasting reduction in the behavioural response to formalin injection, and a parallel reduction in the NK1 receptor immunoreactivity normally observed in spinal dorsal horn. Intrathecal SP in the control groups, i.e., rats treated with an oligonucleotide containing four mismatched bases, the corresponding sense oligonucleotide, a mixture of the sense and the antisense oligonucleotides, in each case had no effect. The effects of SP were blocked by NK1 receptor antagonists and were not mimicked by NMDA. The mechanism underlying these effects is not clear. It may be due to partial degradation of the internalised receptors, which cannot be replaced by newly synthesised receptors because of the action of the NK1 antisense oligonucleotide.

Animals↗

PubMed1998

Effect of continuous spinal remifentanil infusion on behaviour and spinal glutamate release evoked by subcutaneous formalin in the rat.

Injection of formalin into the hind paw of the rat evokes a biphasic nociceptive behavioural response, which is considered to be an animal model of postoperative pain in humans. The initial response (phase 1) is caused by activation of peripheral nociceptors and is followed by a second phase attributed to ongoing activity in primary afferents and increased sensitivity of dorsal horn neurones. The latter effect is thought to result from glutamate-mediated N-methyl-D-aspartate receptor activation. In studies to date it has been difficult to discriminate mechanisms underlying phase 1 and phase 2 events because of the long-lasting half-times of intrathecally administered opioids. To further understanding of the opioid pharmacology of the two different phases of the formalin test, we have studied behavioural activity and spinal glutamate release after intrathecal administration of remifentanil, a new short-lasting mu opioid. Intrathecal remifentanil 3 micrograms microliter-1 min-1 delivered during phase 1 inhibited behavioural response during phase 1 (100%), but did not abolish subsequent phase 2 behavioural activity completely (67 (12) %). Intrathecal remifentanil administered separately in phase 1 and phase 2 revealed a similar ED50 (0.2 microgram microliter-1 min-1) for inhibition of the behavioural responses. In vivo, spinal microdialysis showed incomplete reduction in glutamate concentrations in response to intrathecal remifentanil administration; this in turn inhibited phase 1 behavioural responses. Therefore we contend that supramaximal doses of intrathecal remifentanil sufficient to inhibit phase 1 activity still permitted sufficient glutamate release to allow spinal facilitation. Incomplete suppression of spinal excitatory neurotransmitter release by intrathecal opioids is consistent with spinal wind-up that is triggered during phase 1 and results in phase 2 afferent drive. This might reflect one of the mechanisms underlying post-operative pain.

Analgesics, Opioid↗

PubMed1997

Audiogenic seizures after neck tourniquet-induced cerebral ischemia in the rat.

Development of audiogenic seizures (AGS) and their correlation with neurodegeneration were studied after 7.5 min of whole-brain ischemia. One day post-ischemia, all animals became hyperreactive and responded to auditory stimulation by generalized seizures. Neuronal necrosis developed already 6 h post-ischemia in inferior colliculi, reticular thalamic nucleus and hippocampal hilar region. Repeated ischemia did not induce any neurological changes, suggesting that the neurological effects are consequences of selective neuronal injury.

Acoustic Stimulation↗

PubMed1997

Technique of selective spinal cord cooling in rat: methodology and application.

In a number of interventions, it is desirable to be able to produce a rapid but readily reversible change in spinal cord temperature (SCT) without altering general body temperature and to maintain this selective spinal cord hypothermia stable for an extended interval. To accomplish this, we developed a technique of subcutaneous perfusion cooling in rat. This was accomplished by constructing a copper heat exchanger which was readily implanted into subcutaneous space overlying the upper thoracic to upper sacral spinal segments. The heat exchanger was then perfused with fluid from an external temperature bath maintained at (8 degrees C) at a perfusion rate of 100 ml/min. The temperature of the heat exchanger was controlled by regulating the pump with a feed back controller driven by a thermocouple placed percutaneously into the paraspinal musculature. A series of studies were performed to demonstrate the characteristics and utility of this cooling technique. Lowering the pump set point to 24 degrees C resulted in a fall in the intrathecal temperature (ITT) to 27 +/- 0.3 degrees C within 15 min with no significant changes observed in rectal temperature (37.5- > 37.2 degrees C). Change in intrathecal temperature showed a highly significant correlation with changes in paravertebral muscle temperature (r = 0.977). The hypothermic state could be readily maintained for extended intervals up to 5 h and an underbody heating pad was used to maintain rectal temperature between 35-36.5 degrees C. Lowering the ITT from 37 degrees C-27 degrees C evoked a temperature-dependent increase in the latency of precooling spinal somatosensory evoked potentials (SSEPs) with the highest sensitivity observed in postsynaptic components. Returning the set point temperature back to 37 degrees C produced a rapid recovery of the SSEPs latencies. Consistent with previously published data, selective spinal cord hypothermia (27 degrees C) provided complete protection against otherwise injurious interval of normothermic ischemia produced by balloon occlusion of the descending aorta. This technique provides a simple, relatively non-invasive and reliable experimental tool for studying the effect of selective, acute and/or prolonged spinal cord hypothermia.

Animals↗

PubMed1997

Knee joint inflammation attenuates spinal FOS expression after unilateral paw formalin injection in rat.

Carrageenan-induced knee joint inflammation evoked a transient spinal FOS protein expression in neurons localized in the apical region of laminae I-III with peak activity observed 2 h after inflammation. Consistent with previously published observations, paw formalin injection evoked a distinct pattern of FOS protein expression in L3-L5 spinal segments. The majority of FOS-positive neurons were localized in the superficial dorsal horn (laminae I-II). Laminae V and VI contained moderate numbers of labeled neurons and only a few labeled nuclei were visible in laminae VII-X. In contrast, ipsilateral paw formalin injection, if administered 4 h after carrageenan-induced knee inflammation, evoked significantly fewer FOS positive neurons in all laminar and segmental levels analyzed as compared with formalin injected animals but without previous knee joint inflammation. These data indicate that primary acute or subacute nociceptive input may evoke central processes that are characterized by an inducible form of central inhibition which then may serve to modulate the subsequent spinal effect of superimposed nociceptive peripheral stimulation.

Animals↗

PubMed1997

Spinal cord gray matter layers rich in NADPH diaphorase-positive neurons are refractory to ischemia-reperfusion-induced injury: a histochemical and silver impregnation study in rabbit.

Silver impregnation analysis of neuronal damage and concurrent histochemical characterization of NADPH diaphorase-positive neuronal pools in the rabbit lumbosacral segments was performed during and after transient spinal cord ischemia. Strongly enhanced staining of NADPH diaphorase-positive neurons and their processes appeared in the superficial dorsal horn (laminae I-III), the pericentral region (lamina X) of lower lumbar segments, the lateral collateral pathway, and mainly in neurons of the sacral parasympathetic nucleus in the S2 segment at the end of 40 min of abdominal aorta ligation or 1 day after reperfusion. Despite the development of extensive neuronal degeneration in the central gray matter (laminae IV-VII) between 1 and 4 days after ischemia, a number of nonnecrotizing neurons localized in the areas corresponding with the distribution of NADPH diaphorase-positive neurons was detected, suggesting a selective resistance of these classes of neurons against transient ischemic insult. While the precise mechanism of the observed resistance is not known, it is postulated that region-specific synthesis of nitric oxide and its vasodilatatory effect during the period of incomplete spinal ischemia may account for the observed selective resistance of these spinal cord neurons to transient ischemia.

Animals↗

PubMed1997

Neuroprotective effect of graded postischemic reoxygenation in spinal cord ischemia in the rabbit.

Early ischemia/reperfusion-induced changes of four phospholipid compounds bound to the inner cell membrane leaflet, i.e., phosphatidic acid, inositol phospholipids, serine phospholipids, and ethanolamine plasmalogens, were studied in a model of spinal cord ischemia in the rabbit during normoxic and graded postischemic reoxygenation. Light and electron microscopic analysis after normoxic reoxygenation disclosed neuronal membrane argyrophilia of the interneuronal pool located in lamina VII of L4-L6 segments. The number of small neurons (10-25 microm in diameter) affected by somatodendritic argyrophilia was greatly reduced, and concomitantly the ultrastructure of the endoplasmic reticulum, mitochondria, and Golgi complexes remained almost undamaged when graded postischemic reoxygenation had been applied. A statistically significant increase of phosphatidylserine and ethanolamine plasmalogen levels, and a decrease of phosphatidic acid, were detected after a short-lasting graded postischemic reoxygenation. The formation of thiobarbituric acid-reactive substances was significantly reduced during 60 min of graded postischemic reoxygenation and remained close to control or ischemic levels. The present data indicate that graded postischemic reoxygenation, which is considered to be neuroprotective, can prevent neuronal argyrophilia and the development of reperfusion-induced alterations of organelles. Moreover, reoxygenation can positively modify ischemia-induced changes of some membrane-bound phospholipids.

Animals↗

PubMed1996

Spinal amino acid release and precipitated withdrawal in rats chronically infused with spinal morphine.

Glutamate receptors are implicated in the genesis of opioid tolerance and dependence. Factors governing release of amino acids in systems chronically exposed to opiates, however, remain undefined. Using rats, each prepared with a spinal loop dialysis catheter and with a chronic lumbar intrathecal infusion catheter connected to a subcutaneous minipump, the release of amino acids before and during antagonist-precipitated withdrawal in unanesthetized rats was examined. Spinal infusion of morphine (20 nmol/micro l/hr) for 4 d had little effect on resting release of amino acids. In morphine-infused, but not saline-infused, rats naloxone (2 mg/kg, i.p.) evoked an immediate increase in the release of L-glutamate (299 +/- 143%) and taurine (306 +/- 113%) but not other amino acids. The magnitude and time course of the release of these amino acids significantly correlated with behavioral indices of withdrawal intensity. Acute intrathecal pretreatment immediately before naloxone with clonidine (20 microg; alpha2 agonist), MK-801 (3 microg; noncompetitive NMDA antagonist), or aminophosphonopentanoic acid (AP-5; 3 microg; competitive NMDA antagonist) suppressed naloxone-induced increases in spinal L-glutamate and taurine release and behavioral signs of withdrawal in spinal morphine-infused rats. Results point to a correlated increase in spinal L-glutamate release, which contributes to genesis of the opioid withdrawal syndrome. Agents such as clonidine that suppress opioid withdrawal may owe their action to an inhibition of excitatory amino acid release. The effects of MK-801 and AP-5 suggest a glutamate-evoked glutamate release.

Amino Acids↗