The effects of bicuculline on the isolated spinal cord of the frog

An investigation has been made of the effects of topically applied bicuculline, a reported gamma-aminobutyric acid (GABA) antagonist, on the isolated, hemisected frog spinal cord by recording ventral and dorsal root potentials and reflexes evoked by volleys to various spinal cord inputs. Bicuculline had potent excitatory effects causing depolarization, spontaneous potentials in ventral and dorsal roots, and an increased polysynaptic ventral root reflex. More importantly, the alkaloid blocked presynaptic inhibition of orthodromic reflex activity produced by preceding ventral root stimulation and primary afferent depolarization. These effects were attributed to a demonstrated antagonism of the direct depolarizing effects of GABA on dorsal root terminals by the alkaloid. These actions of bicuculline suggest that GABA may be the transmitter responsible for primary afferent depolarization and presynaptic inhibition in the amphibian.     

Effects of Vigabatrin (γ-vinyl GAB A) on Neuro transmission-Related Amino Acids and on GAB A nd Benzodiazepine Receptor Binding in Rats

The effect of 12-day intraperitoneal i.p. administration of vigabatrin (GVG, gamma-vinyl GABA) to rats on the neurotransmission-related amino acids in various brain regions (cortex, hippocampus, cerebellum, and spinal cord), cisternal fluid (CSF) and blood was studied. Results showed that GVG administration increased the levels of GABA in cortical and subcortical regions of the brain and CSF without affecting GABA and benzodiazepine receptors in the cortex. In addition, a dose-dependent decrease was noted in the concentration of glutamate in the hippocampus and in the concentrations of aspartate and glutamine in the cortex, hippocampus, and cerebellum. The changes in the levels of amino acids in the brain, except for that of GABA, were not reflected in the CSF, however, and the levels of amino acids in discrete brain regions did not show any correlation with those in the serum or in the CSF. The results suggest that GVG administration might suppress development and spread of seizures not only by elevating the level of the inhibitory amino acid GABA, but also by decreasing the levels of excitatory amino acids in the brain.     

Some actions of catechol on synaptic transmission in the isolated spinal cord of the frog.

The isolated frog spinal cord was used to investigate the synaptic effects of the convulsant agent catechol. Addition of the compound to the superfusate consistently enhanced orthodromic reflex activity recorded from ventral roots and augmented primary afferent depolarization. Concomitantly catechol altered the polarization changes produced in ventral and dorsal roots by putative neurotransmitter amino acids when these compounds were applied in Mg2+-containing Ringer. Catechol reduced the hyperpolarizations induced in motoneurons by the neutral amino acids, GABA, beta-alanine, taurine and glycine, but did not affect the depolarizations produced by the dicarboxylic amino acids, L-glutamate and L-aspartate. In contrast, catechol increased the dorsal root depolarizations elicited by both neutral and dicarboxylic amino acids and also the depolarizations produced by elevated potassium concentrations. Catechol did not bring about significant changes in the passive electrical properties of motoneurons or dorsal root fibers. In addition, it did not alter either the high affinity uptake or the depolarization-evoked release of tritiated GABA, glycine, L-glutamate and L-aspartate. It appears that the postsynaptic actions of catechol explain its ability to enhance spinal reflexes.     

Opioid peptides decrease calcium-dependent action potential duration of mouse dorsal root ganglion neurons in cell culture

Opiate alkaloid and opioid peptide actions on spontaneous neuronal activity and postsynaptic amino acid responsiveness were assessed using intracellular recording techniques applied to murine spinal cord neurons in primary dissociated cell culture. Application of opiates was by superfusion and amino acids by iontophoresis. Glycine and GABA but not glutamate responses were antagonized by the opiate alkaloids. Since opiate effects on glycine and GABA responses were not naloxone-reversible, only weakly stereospecific, and not produced by the opioid peptide [d-Ala²]-Met-enkephalinamide, it is unlikely that these effects were mediated by opiate receptors. Opiate depression of glycine inhibition was correlated with the induction of paroxysmal depolarizations in cultured spinal cord neurons, suggesting that antagonism of inhibitory amino acid transmission may underlie the convulsant actions of high concentrations of the opiate alkaloids.     

Spinal 5-HT3 receptor-mediated antinociception: possible release of GABA

Although 5-HT is clearly involved in spinal analgesia, its mode of action remains obscure, perhaps because it has multiple and often opposing effects mediated by its multiple receptor subtypes. This investigation uses selective agonists and antagonists directed at the most recently defined class of 5-HT receptors (5-HT3 receptors) in behavioral and electrophysiological studies of nociception in the spinal cord of rodents. The results demonstrate uniformly inhibitory effects of a selective 5-HT3 agonist on responses to noxious stimuli. Intrathecally administered 2-methyl 5-HT produced dose-dependent antinociception in the tail-flick test and inhibited behaviors elicited by intrathecally administered agonists for excitatory amino acid and neurokinin receptors, namely NMDA and substance P (SP). All 20 dorsal horn neurons we examined, which projected to the brain and responded to both noxious stimuli and NMDA, were inhibited in a current-related manner by this 5-HT3 agonist applied iontophoretically. Both the behavioral and electrophysiological effects were blocked not only by the 5-HT3 antagonists zacopride and ICS 205-930, but also by antagonists to the inhibitory amino acid GABA. Therefore, 5-HT via an action at 5-HT3 receptors may evoked release of GABA, which may in turn inhibit nociceptive transmission at a site postsynaptic to terminals of primary afferent fibers. If the descending serotonergic analgesic system in humans operates similarly, understanding it may enable the development of new nonopioid, nonaddictive analgesics.     

Distribution pattern of inhibitory and excitatory synapses in the dendritic tree of single masseter alpha-motoneurons in the cat.

Little is known about the differences in the distributions of inhibitory and excitatory synapses in the dendritic tree of single motoneurons in the brainstem and spinal cord. In this study, the distribution of gamma-aminobutyric acid (GABA)-, glycine-, and glutamate-like immunoreactivity in axon terminals on dendrites of cat masseter alpha-motoneurons, stained intracellularly with horseradish peroxidase, was examined by using postembedding immunogold histochemistry in serial ultrathin sections. The dendritic tree was divided into three segments: primary (Pd) and distal (Dd) dendrites and intermediate (Id) dendrites between the two segments. Quantitative analysis of 175, 279, and 105 boutons synapsing on 13 Pd, 54 Id, and 81 Dd, respectively, was performed. Fifty percent of the total number of studied boutons were immunopositive for GABA and/or glycine and 48% for glutamate. Among the former, 27% showed glycine immunoreactivity only and 14% were immunoreactive to both glycine and GABA. The remainder (9%) showed immunoreactivity for GABA only. As few as 3% of the boutons were immunonegative for the three amino acids. Most boutons immunoreactive to inhibitory amino acid(s) contained a mixture of spherical, oval, and flattened synaptic vesicles. Most boutons immunoreactive to excitatory amino acid contained clear, spherical, synaptic vesicles with a few dense-cored vesicles. When comparisons of the inhibitory and excitatory boutons were made between the three dendritic segments, the proportion of the inhibitory to the excitatory boutons was high in the Pd (60% vs. 37%) but somewhat low in the Id (46% vs. 52%) and Dd (44% vs. 53%). The percentage of synaptic covering and packing density of the inhibitory synaptic boutons decreased in the order Pd, Id, and Dd, but this trend was not applicable to the excitatory boutons. The present study provides possible evidence that the spatial distribution patterns of inhibitory and excitatory synapses are different in the dendritic tree of jaw-closing alpha-motoneurons.     

gamma-Hydroxybutyric acid is not a GABA-mimetic agent in the spinal cord.

gamma-Hydroxybutyric acid (GHB), a pharmacologically active central nervous system constituent, has been postulated to function as a gamma-aminobutyric acid (GABA) agonist. This hypothesis was tested directly on GABAergic synapses in isolated, superfused frog spinal cord. Addition of GHB to the superfusate produced effects on primary afferent terminals that were distinctly different from the effects of GABA. Thus, although both compounds depressed dorsal root potentials, GHB hyperpolarized terminals while GABA depolarized the same structures. The GABA responses were antagonized by bicuculline and picrotoxin, but these alkaloids did not change GHB's actions. In addition, GHB altered neither high-affinity uptake by cord slices, nor potassium-evoked release of tritiated GABA from them. GHB did not directly release GABA from spinal slices preloaded with [3H]GABA. These observations suggest that the central nervous system actions of GHB are not dependent upon its ability to activate GABAergic synapses or to modify GABAergic mechanisms.     

Antispasticity drugs: mechanisms of action

Several different drugs are now used, or are potentially useful, to treat patients with spasticity. Although these compounds vary in their actions on spinal neurons and reflex arcs, it is possible to formulate reasonable hypotheses regarding their modes of action. The benzodiazepines bind to specific benzodiazepine receptors linked to classic gamma-aminobutyric acid (GABA) receptors located on the terminals of primary afferent fibers. This binding results in an increased affinity of the GABA receptor for the amino acid, an augmented flux of chloride ions across the terminal membrane, and an increase in the amount of presynaptic inhibition. Baclofen activates GABAB receptors putatively located on the same terminals. Activation of these receptors retards the influx of calcium ions into the terminals, thereby reducing the evoked release of excitatory amino acids and possibly other transmitters. Progabide and its metabolites act on both classic and GABAB receptors. Glycine works on specific inhibitory receptors located on spinal interneurons and motoneurons. The phenothiazines act on the brainstem to alter the function of fusimotor fibers. Phenytoin and carbamazepine reduce the afferent output of muscle spindles. Dantrolene diminishes the activation of the contractile process in muscle fibers by reducing the release of calcium ions from the sarcoplasmic reticulum. This review summarizes the data supporting these concepts.     

Effects of amino acids on the excitability of respiratory bulbospinal neurons in solitary and para-ambigual regions of medulla in cat

The effects of inhibitory (gamma-aminobutyric acid (GABA) and glycine) and excitatory (L-glutamate and DL-homocysteate, DLH) amino acids on the excitability of respiratory bulbospinal neurons were studied in decerebrate, paralyzed, bilaterally vagotomized, artificially ventilated cats. Unit activities were recorded extracellularly in the medulla in both the ventrolateral portion of the nucleus tractus solitarius and the para-ambigual region in the vicinity of the nucleus ambiguus (dorsal and ventral respiratory groups, respectively). All neurons were bulbospinal since they could be antidromically activated by electrical stimuli to the spinal cord. We used variations in antidromic latency (ADL) as a measure of changes in excitability of the soma. All neurons exhibited variations in ADL related to the respiratory cycle, being shortest (minimum ADL) during neural activity and longest (maximum ADL) in the silent period. Neurons whose discharge frequencies fell during application of putative inhibitory amino acids showed an increase of minimum ADL compared to control, indicating hyperpolarization. Minimum ADL, in some cells, became shorter during application of excitatory amino acids, indicating depolarization; in others, mechanisms secondary to increased neuronal firing likely obscured their effects. The transient maximum ADL usually present at the onset of the silent period was increased by excitatory amino acids and, in some units, was reduced or eliminated by inhibitory amino acids. These effects are discussed in terms of a modulation by synaptic inputs and neurotransmitters of the cumulative afterhyperpolarization which follows bursts of action potentials.     

Neurochemical aspects of post-tetanic potentiation of monosynaptic reflexes in the cat spinal cord. III. Analysis of amino acids after long-term potentiation.

Following 30-min intermittent post-tetanic potentiation of monosynaptic reflexes in the ventral horn of the spinal cord of 10 cats, the amino acid composition was analyzed after reacting with 14C-dansylchloride and by two-dimensional chromatography. The amino acids in comparable segments of the spinal cord from eight animals after ether anesthesia and from five animals who were operated on but not stimulated were also analyzed. In the latter the operation itself influenced the amino acid composition as compared to those animals who were anesthetized. Comparison between the different control groups showed that the operated animals can be used as a control for calculation of the changes caused by potentiation. The amino acids glycine, glutamic acid and aspartic acid, which act as either inhibitory or excitatory neurotransmitters, increased significantly after potentiation, as did the amino acids lysine, histidine, leucine, isoleucine, and proline.     

Hypothalamic substance P-containing neurons. Sex-dependent topographical differences and ultrastructural transformations associated with stages of the estrous cycle

Spontaneous dorsal root potentials (sDRPs) were recorded from the dorsal roots of the isolated frog spinal cord using sucrose gap techniques. sDRPs were always negative (depolarizing) in sign and ranged in size from about 100 microV to 6.0 mV. The largest sDRPs were 25-40% of the amplitude of DRPs evoked by stimulation of adjacent dorsal roots. Hypoxia or accumulation of extracellular K+ ions did not appear responsible for the generation of this spontaneous activity since exposing the cord to unoxygenated Ringer's solution decreased sDRPs and K+-sensitive microelectrodes indicated that only small changes in extracellular K+ (approximately 0.15 mM) were produced coincidently with the largest sDRPs. Chemically-mediated synaptic transmission was found to be necessary for the production of sDRPs because the addition of Mn2+ or Mg2+ ions or tetrodotoxin to the Ringer's solution or reduction of its Na+ concentration blocked sDRPs, whereas application of 4-aminopyridine enhanced them. It did not seem that a direct action of GABA on afferent fiber terminals was responsible for the generation of spontaneous potentials since an increase in sDRPs was seen after: application of the GABA antagonists, bicuculline and picrotoxin; exposure to the glutamic acid decarboxylase inhibitor, semicarbazide (which significantly reduced the concentration of GABA in the cord); and lowering of the external Cl- concentration. Similarly taurine is probably not significant since the taurine antagonist, TAG, increased the amount of spontaneous activity. On the other hand, (--)-baclofen, which is thought to reduce excitatory amino acid release, D,L-alpha-aminoadipic acid, alpha, epsilon-diaminopimelic acid, and 2-amino-4-phosphonobutyric acid, which are believed to be selective postsynaptic excitatory amino acid antagonists, and [D-Pro2-D-Phe7-D-Trp9]-substance P, a postsynaptic blocker of the action of substance P, markedly and reversibly reduced sDRPs. Experiments were performed on isolated cords without supraspinal or afferent input; therefore sDRPs must be generated by intraspinal structures. It would seem that interneurons are responsible because addition of mephenesin or pentobarbital--compounds which inhibit polysynaptic reflex transmission involving interneurons--reduced the production of sDRPs. sDRPs may result from the action of excitatory transmitters such as L-glutamate, L-aspartate, or substance P released by interneuronal firing in the spinal cord. Moreover, because sDRPs were increased by application of yohimbine, corynanthine and propanolol and reduced by haloperidol, such interneurons may be under descending control of adrenergic and dopaminergic fibers.     

Interactions of norepinephrine with Purkinje cell responses to putative amino acid neurotransmitters applied by microiontophoresis

In cerebellum, the evoked responses of the Purkinje neuron to both excitatory and inhibitory afferent input are enhanced by local norepinephrine (NE) administration. To determine the nature of this synergistic interaction between NE and the synaptic inputs, Purkinje cell responses to microiontophoretically applied amino acid neurotransmitters were examined before, during, and after NE iontophoresis. NE was found to preferentially augment GABA-induced inhibition, whereas it antagonized inhibition produced by glycine. This enhancement of GABA inhibition was seen at NE doses which caused minimal change in spontaneous activity, and at times after spontaneous discharge returned to control levels following NE application. Dopamine did not facilitate the response to GABA even at doses having direct depressant effects on spontaneous discharge. Glutamate-evoked excitations and subsquent depressions were also augmented during NE administration, relative to the level of background activity. Thus, NE selectively enhanced responses of Purkinje neurons produced by microiontophoretic application of amino acids postulated to be cerebellar neurotransmitters, supporting the hypothesis that NE acts on postsynaptic processes to increase the responsiveness of the Purkinje cell to afferent input. These data also provide evidence supporting the concept that a primary effect of noradrenergic input to cerebellum may be to modulate the action of other transmitters.     

Serotonin-induced depolarization of rat facial motoneurons in vivo: Comparison with amino acid transmitters

Intracellular recordings were obtained from facial motoneurons in anesthetized rats. The effects of iontophoretically applied serotonin were compared to those of the excitatory amino acids glutamate and DL-homocysteic acid (DLH), and the inhibitory amino acids, glycine, GABA and muscimol, under various conditions of membrane polarization and intracellular chloride concentration. Iontophortically applied serotonin caused a depolarization of facial motoneurons which was accompanied by increased input resistance and increased neuronal excitability. Experiments comparing the response to serotonin with those of glycine, GABA, and muscimol demonstrated that the serotonin effect does not involve changes in membrane conductance to chloride. Comparisons of serotonin with glutamate and DLH at varying levels of membrane hyperpolarization indicated that the serotonin-induced depolarization is not caused by increased conductance to sodium or calcium, and differs in its underlying ionic mechanism from depolarizations induced by glutamate and DLH. Results were consistent with the hypothesis that serotonin causes depolarization, increased input resistance, and increased excitability in rat facial motoneurons by decreasing resting membrane conductance to potassium ions. Such changes in motoneurons in the brain stem and spinal cord probably account for some of the physiological and behavioral effects observed during pharmacological activation of serotonin receptors.     

The presynaptic effects of valproic acid in the isolated frog spinal cord

The effects of the anticonvulsant valproic acid (n-dipropylacetate, DPA) on frog primary afferent fibers was examined with sucrose gap recordings from the dorsal roots. Addition of DPA to the superfusate consistently reduced the amplitude and duration of the dorsal root potential. In contrast, DPA augmented the depolarization of dorsal roots produced by GABA, β-alanine and taurine. It also decreased afferent fiber ‘desensitization’ to GABA. DPA depressed the ability of K⁺ and the excitatory amino acids glutamate and aspartate to depolarize afferent fibers. In addition, the compounds decreased the amount of K⁺ released by tetanic stimulation of the dorsal root.

The K⁺-evoked release of tritiated GABA from cord slices was initially reduced by exposure to DPA, but was then unaffected after a longer application of the anticonvulsant. On the other hand, the high affinity uptake of tritiated GABA and glycine were almost totally blocked by the addition of DPA to the incubating medium.

In sum, DPA has complex effects on neuronal membranes. Some of these effects may serve to explain the anticonvulsant actions of this drug.     

Inhibitory postsynaptic actions of taurine, GABA and other amino acids on motoneurons of the isolated frog spinal cord.

The actions of glycine, GABA, alpha-alanine, beta-alanine and taurine were studied by intracellular recordings from lumbar motoneurons of the isolated spinal cord of the frog. All amino acids tested produced a reduction in the amplitude of postsynaptic potentials, a blockade of the antidromic action potential and an increase of membrane conductance. Furthermore, membrane polarizations occurred, which were always in the same direction as the IPSP. All these effects indicate a postsynaptic inhibitory action of these amino acids. When the relative strength of different amino acids was compared, taurine had the strongest inhibitory potency, followed by beta-alanine, alpha-alanine, GABA and glycine. Topically applied strychnine and picrotoxin induced different changes of post-synaptic potentials, indicating that distinct inhibitory systems might be influenced by these two convulsants. Interactions with amino acids showed that picrotoxin seletively diminished the postsymaptic actions of GABA, while strychnine reduced the effects of taurine, glycine, alpha- and beta-alanine. But differences in the susceptibility of these amino acid actions to strychnine could be detected: the action of taurine was more sensitively blocked by strychnine compared with glycine, alpha- and beta-alanine. With regard to these results the importance of taurine and GABA as transmitters of postsynaptic inhibition on motoneurons in the spinal cord of the frog is discussed.     

Neurochemical aspects of post-tetanic potentiation of monosynaptic reflexes in the cat spinal cord. I. Analysis of amino acids at maximum of potentiation.

In order to determine the chemical changes which might occur during post-tetanic potentiation, amino acids from the motor regions of the ventral horn of the spinal cord (potentiated and unpotentiated sides) of 10 different cats were analyzed. The intermittent tetanic stimulation of the Nn. gastroc. (only on the potentiated side) was carried out until a maximum of potentiation was reached (3--4 min). The monosynaptic reflexes were obtained from the ventral roots (L7 or S1) of both sides. The amino acids of the potentiated side were compared to those of the unpotentiated side (control) using a 14-C-dansyl chloride procedure. The two main amino acids considered to be excitatory neurotransmitters, glutamic acid and aspartic acid, showed a more than 20 per cent increase on the potentiated side as compared to the control side. Glycine, which plays an inhibitory role, especially in the spinal cord, reacted with 6 per cent decrease, whereas GABA which is also considered as an inhibitory neurotransmitter showed a change of + 11 per cent on the potentiated side as compared to the unpotentiated side. The importance of the potentiation time for those changes is pointed out.     

Increases in GABA concentrations during cerebral ischaemia: a microdialysis study of extracellular amino acids

OBJECTIVES: Increases in the extracellular concentration of the excitatory amino acids glutamate and aspartate during cerebral ischaemia in patients are well recognised. Less emphasis has been placed on the concentrations of the inhibitory amino acid neurotransmitters, notably gamma-amino-butyric acid (GABA), despite evidence from animal studies that GABA may act as a neuroprotectant in models of ischaemia. The objective of this study was to investigate the concentrations of various excitatory, inhibitory and non-transmitter amino acids under basal conditions and during periods of cerebral ischaemia in patients with head injury or a subarachnoid haemorrhage. METHODS: Cerebral microdialysis was established in 12 patients with head injury (n=7) or subarachnoid haemorrhage (n=5). Analysis was performed using high performance liquid chromatography for a total of 19 (excitatory, inhibitory and non-transmitter) amino acids. Patients were monitored in neurointensive care or during aneurysm clipping. RESULTS: During stable periods of monitoring the concentrations of amino acids were relatively constant enabling basal values to be established. In six patients, cerebral ischaemia was associated with increases (up to 1350 fold) in the concentration of GABA, in addition to the glutamate and aspartate. Parallel increases in the concentration of glutamate and GABA were found (r=0.71, p<0.005). CONCLUSIONS: The results suggest that, in the human brain, acute cerebral ischaemia is not accompanied by an imbalance between excitatory and inhibitory amino acids, but by an increase in all neurotransmitter amino acids. These findings concur with the animal models of ischaemia and raise the possibility of an endogenous GABA mediated neuroprotective mechanism in humans.     

Effects of D,L-alpha-aminoadipate on postsynaptic amino acid responses in cultured mouse spinal cord neurons

The effects of the dicarboxylic amino acid, DL-alpha-aminoadipate (DLAA) on amino acid responses have been investigated using intracellular recordings from mouse spinal cord neurons grown in dissociated cell culture. DL-alpha-Aminoadipate markedly antagonized postsynaptic responses to iontophoretically appllied aspartate; antagonism of glutamate was much less prominent. DL-alpha-Aminoadipate altered the affinity of aspartate for its receptor while having no observed effects on aspartate-receptor cooperativity. No direct effects of DLAA on membrane potentials or passive membrane properties were seen at the currents used for antagonism. Responses to the inhibitory amino acids GABA and glycine were unaffected by DLAA.     

Hypoxia increases extracellular concentrations of excitatory and inhibitory neurotransmitters in subsequently induced seizure: in vivo microdialysis study in the rabbit.

It is uncertain whether a brief hypoxic exposure exerts long lasting effects on central nervous system amino acid neurotransmission. The purpose of this study was to test the hypothesis that a short period of hypoxia would affect release of excitatory and inhibitory amino acids during subsequent bicuculline-induced seizure. Utilizing in vivo microdialysis in cerebral cortex of rabbits, we observed no significant increase in extracellular fluid (ECF) concentrations of the excitatory amino acids, glutamate and aspartate, or the inhibitory amino acids, GABA and taurine, during a 30-min exposure to hypoxia (FiO2 = 0.08). In addition, there was no significant change in these amino acids during uncomplicated seizure. However, when seizure was complicated by a preceding period of hypoxia, there was a marked and progressive rise in both excitatory and inhibitory amino acids in ECF. We conclude that a short period of hypoxia, which itself does not cause changes in ECF concentrations of excitatory amino acids, may nonetheless contribute to neuronal injury by altering the levels of ECF amino acids during a subsequent insult.     

Neurogenic bladder model for spinal cord injury: spinal cord microdialysis and chronic urodynamics

We describe an animal model to study neurotransmitter changes in parallel with urodynamic testing following Spinal Cord Injury (SCI). Urodynamic access was achieved using a subcutaneously placed 7 French dual lumen portacatheter. Spinal cord injury was induced by weight drop technique onto exposed dura at T8. The L6-S1 detrusor nuclei were localized stereotactically and microdialysis probe placement was confirmed through histologic methods. Chronic urodynamics revealed detrusor hyperreflexia (DH) 14 days following SCI. In vivo microdialysis of spinal cord amino acids was performed using CMA 11 (240 uM) probes in halothane-anesthetized rats at baseline and intervals of 20-30 min following spinal cord injury. Significant increases in the excitatory amino acid glutamate, and the inhibitory amino acids, glycine and taurine, were seen following spinal cord injury. Amino acid levels peaked at approximately 40 min following contusion injury with glycine demonstrating the highest levels of all amino acids measured. This neurogenic rat model provides a useful means of examining the effects of spinal cord injury on bladder function. By utilizing spinal cord microdialysis, one could intervene at the level of the detrusor nuclei to modulate bladder function.