Excitatory Amino Acid Binding Research Articles

3H- l-Glutamate Binding and 3H- d-Aspartate Release From Hippocampal Tissue During the Development of Pentylenetetrazole Kindling in Rats

Previous studies have proposed that there is an increase in the density of glutamate binding sites after pentylenetetrazol (PTZ) kindling, whereas the glutamate release is not altered. Little is known about the time course of these changes. Therefore, we studied 3H-L-glutamate binding to hippocampal membranes and K+-stimulated 3H-D-aspartate release from hippocampal slices of rats given PTZ 3, 7, and 13 times up to a fully kindling state. After three PTZ injections, amino acid release from hippocampal tissue slices was significantly enhanced in comparison to controls, whereas 3H-L-glutamate binding was not altered. After seven injections of PTZ, specific glutamate binding to hippocampal membranes tended to increase, and K+-stimulated 3H-D-aspartate release from rat hippocampal slices was normalized. The kindled state characterized by generalized clonic-tonic seizures was reached after 13 PTZ injections, and it was accompanied by an enhancement in the density of glutamate binding sites, whereas the chemically evoked amino acid release remained unchanged. It can be concluded that the amino acid release is increased in the early phase of PTZ kindling development, whereas after completion of kindling, the density of excitatory amino acid binding sites is enhanced.

Chronic treatment with a classical neuroleptic alters excitatory amino acid and GABAergic neurotransmission in specific regions of the rat brain

The purpose of the following experiments was to describe some of the neurochemical changes that occur in the basal ganglia of rats exposed chronically to a classical neuroleptic, fluphenazine, and to relate these changes to extrapyramidal motor dysfunction. For these studies a combination of behavioural, receptor autoradiographic and in situ hybridization methods were employed. Preliminary pharmacological studies on GABA receptors showed that incubation in Tris-acetate rather than Tris-citrate buffer increased the number of binding sites labelled by [3H]muscimol by over 120% without affecting binding affinity or selectivity. The results of experiments with fluphenazine showed that treatment for six months increased the frequency of vacuous chewing movements compared to controls. In the striatum, changes in GABA transmission were observed in fluphenazine-treated rats with increases in glutamate decarboxylase mRNA levels in the caudate nucleus, dorsal shell and core of the accumbens and decreases in [3H]muscimol binding in the caudate and dorsal shell regions. These data suggest that fluphenazine treatment increased GABA transmission in specific subregions of the caudate and accumbens nuclei. In addition, glutamate decarboxylase mRNA levels were elevated in the entopeduncular nucleus of fluphenazine-treated animals. Autoradiographic analysis of excitatory amino acid binding showed that fluphenazine exposure decreased [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding in entopeduncular nucleus and in the ventrolateral thalamic nucleus and decreased [3H]dizocilpine maleate binding in the medial geniculate nucleus. These experiments show that in addition to altering GABA transmission, chronic neuroleptic exposure alters excitatory amino acid transmission in specific regions of the basal ganglia-thalamocortical motor system. The neuroleptic dependent increases in glutamate decarboxylase mRNA levels in the entopeduncular nucleus may reflect changes in neurotransmission in the indirect pathway connecting the major input and output nuclei of the basal ganglia. Changes in some of these brain regions may be related to the occurrence of extrapyramidal motor disturbances.

The distribution of excitatory amino acid receptors in the normal human midbrain and basal ganglia with implications for Parkinson's disease: a quantitative autoradiographic study using [ 3H]MK-801, [ 3H]glycine, [ 3H]CNQX and [ 3H]kainate

Quantitative receptor autoradiography using [3H]MK-801, [3H]glycine, [3H]CNQX and [3H]kainate was employed to determine the distribution and density of excitatory amino acid (EAA) binding sites in the midbrain and basal ganglia of the normal human nervous system. Detailed knowledge of the anatomy and subtype specificity of glutamate receptors is important both in understanding the normal physiology of basal ganglia neurotransmission and the pathophysiological changes occurring in diseases affecting the basal ganglia such as Parkinson's disease (PD). In PD, glutamate receptor activation may contribute to cell death of dopaminergic neurones in the substantia nigra. In addition, perturbation of glutamate neurotransmission resulting from dopamine depletion in the basal ganglia is likely to contribute to the clinical manifestations of motor dysfunction. The distribution and density of ligand binding representing N-methyl-D-aspartate (NMDA), AMPA (2-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) and kainate receptors has a heterogeneous distribution in the human midbrain and basal ganglia. In the substantia nigra relatively high densities of [3H]MK-801 and strychnine-insensitive [3H]glycine binding sites representing NMDA receptors were present, whereas only moderate densities of [3H]CNQX and [3H]kainate binding sites were present, compared to other regions. In both the medial globus pallidus and subthalamic nucleus, binding sites representing NMDA, AMPA and kainate receptors were all present at low density. These findings suggest that the clinical usefulness of modifying glutamatergic neurotransmission in these basal ganglia nuclei may be limited by the relatively low density of EAA binding sites present.

Pharmacology of morphine and morphine-3-glucuronide at opioid, excitatory amino acid, GABA and glycine binding sites.

Morphine in high doses and its major metabolite, morphine-3-glucuronide, cause CNS excitation following intrathecal and intracerebroventricular administration by an unknown mechanism. This study investigated whether morphine and morphine-3-glucuronide interact at major excitatory (glutamate), major inhibitory (GABA or glycine), or opioid binding sites. Homogenate binding assays were performed using specific radioligands. At opioid receptors, morphine-3-glucuronide and morphine caused an equipotent sodium shift, consistent with morphine-3-glucuronide behaving as an agonist. This suggests that morphine-3-glucuronide-mediated excitation is not caused by an interaction at opioid receptors. Morphine-3-glucuronide and morphine caused a weak inhibition of the binding of 3H-MK801 (non-competitive antagonist) and 125I-ifenprodil (polyamine site antagonist), but at unphysiologically high concentrations. This suggests that CNS excitation would not result from an interaction of morphine-3-glucuronide and high-dose morphine with these sites on the NMDA receptor. Morphine-3-glucuronide and morphine inhibited the binding of 3H-muscimol (GABA receptor agonist). 3H-diazepam and 3H-flunitrazepam (benzodiazepine agonists) binding very weakly, suggesting the excitatory effects of morphine-3-glucuronide and high-dose morphine are not elicited through GABAA receptors. Morphine-3-glucuronide and high-dose morphine did not prevent re-uptake of glutamate into presynaptic nerve terminals. In addition, morphine-3-glucuronide and morphine did not inhibit the binding of 3H-strychnine (glycine receptor antagonist) to synaptic membranes prepared from bovine spinal cord. It is concluded that excitation caused by high-dose morphine and morphine-3-glucuronide is not mediated by an interaction with postsynaptic amino acid receptors.

Implanted NGF-Producing Fibroblasts Induce Catalase and Modify ATP Levels but Do Not Affect Glutamate Receptor Binding or NMDA Receptor Expression in the Rat Striatum

Neurotrophic factors, in particular NGF, have been shown to potently protect against glutamate-receptor-mediated toxicity. In order to further investigate the mechanism of this protection, we investigated the in vivo effects of fibroblasts, genetically modified to secrete NGF and implanted near the striatum, on striatal excitatory amino acid binding and receptor expression, on the induction of the peroxidative enzyme catalase, and on cellular energy metabolism in the striatum. Seven days after implantation into the corpus callosum of either a genetically altered NGF-producing (NGF[+]) or unaltered parental (NGF[-]) fibroblast cell-line, there is a time point at which NGF[+] cells have been shown to prevent excitotoxic insults. At that time point after implantation, we found that NGF[+] grafts caused a marked increase in catalase mRNA expression in and around the NGF[+] grafts. The NGF[+] grafts also reduced basal levels of striatal ATP when compared to the effects of NGF[-] grafts. No changes were observed in [3H]glutamate binding and NMDA receptor mRNA expression. We conclude that effects of NGF[+] fibroblast grafts on glutamate receptor mediated toxicity are not by direct effects on glutamate receptors or glutamate binding, but rather appear to be a process involving enzymatic induction and modification of cellular energy stores. The observed increase in catalase mRNA suggests that peroxidative metabolism may be involved in these NGF-mediated effects.

GABA, muscarinic cholinergic, excitatory amino acid, neurotensin and opiate binding sites in the octavolateralis column and cerebellum of the skate Raja nasuta (Pisces: Rajidae)

As part of a study of signal processing in the electro- and mechanosensory systems we have screened the octavolateralis column of the skate for GABAA, muscarinic cholinergic, excitatory amino acid, neurotensin and opiate binding sites using autoradiography following in vitro labelling of cryostat sections with tritiated ligands. The presence and distribution of these binding sites is compared between the octavolateralis column and the corpus cerebellum. GABAA binding sites were located in high concentrations in the granule cell regions of the cerebellum and octaval columns, with much lower concentrations in the Purkinje cell layer of the corpus cerebellum. Little or no labelling was evident in all molecular layer areas. Displacement studies using the discriminating ligand CL218,872 indicated that the GABAA binding sites were predominantly of the GABAA/benzodiazepine Type II variety. M1 muscarinic cholinergic binding sites were found in high concentrations in all granule cell areas and in lower concentrations in the molecular layer of the octavolateralis column, with an absence of labelling in the molecular layer of the corpus cerebellum. Kainic acid and AMPA binding sites were present in very high concentrations in all molecular layer areas. Glutamate binding was present in the molecular layer of the octavolateralis column and in some restricted regions of the dorsal granular ridge, whereas phencyclidine binding sites were sparse or absent. Neurotensin binding sites were strongly present in all granule cell areas and evident in the molecular layer of the octavolateralis column. There was evidence for opiate binding sites in the molecular layer of both the dorsal and medial octavolateralis nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Glutamate receptors in striatum and substantia nigra: Effects of medial forebrain bundle lesions

We examined NMDA-sensitive [3H]glutamate, [3H]AMPA, [3H]kainate and metabotropic-sensitive [3H]glutamate binding sites in neostriatum and substantia nigra pars reticulata (SNr) in rats after unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. One week after the lesion, NMDA, AMPA, kainate and metabotropic receptors were decreased in the ipsilateral neostriatum, whereas at three months NMDA receptors were increased while AMPA, kainate and metabotropic receptors were not changed. In the SNr at one week, only AMPA and metabotropic receptors were significantly decreased whereas three months after the lesion NMDA, AMPA and kainate binding sites were decreased. The early decrease of excitatory amino acid receptors in the striatum is likely to reflect degeneration of dopaminergic fibers, suggesting that specific subpopulations of excitatory amino acid binding sites are located on dopaminergic terminals.

Excitatory amino acid AMPA receptor mRNA localization in several regions of normal and neurological disease affected human brain. An in situ hybridization histochemistry study

In situ hybridization histochemistry was used to localize the mRNAs coding for four alpha-aminoisoxazole propionic acid-sensitive glutamate receptor subunits in human brain (age range 51-95 years, postmortem delay 4.5-10 h). High levels of the B receptor subunit mRNA were present in all the studied regions, followed by the A-subunit and the C-subunit. Only very low levels of the D-subunit mRNA were detected. In hippocampus, the mRNA coding for the B-subunits of the glutamate receptor was observed in granule cells of dentate gyrus and in the pyramidal cells of Ammon's horn. In cortex, the highest levels of glutamate receptor subunit mRNAs were found in layer I and layers III-IV of entorhinal and temporal cortex, although significant levels were also observed in the other cell layers. A differential distribution was seen in cerebellum where the A-subunit mRNA is expressed mainly by Purkinje cells, while the B-subunit mRNA is present in the internal granule cell layer. These results correlate well with previous data from autoradiographic studies on the localization of excitatory amino acid binding sites in human brain and pinpoint the cells where these receptors are synthesized. In situ hybridization in the hippocampus of patients affected by Alzheimer's disease (age range 77-82 years, postmortem delay 19-25.5 h) revealed a decrease on the content of the mRNAs coding for these excitatory amino acid receptors, while an increase was detected in surgically dissected epileptic human hippocampi. These results corroborate and extend the previous data from in vitro autoradiography and suggest alteration of the excitatory amino acid disfunction during these neurodegenerative processes.

Cerebellar excitatory and inhibitory amino acid receptors in multiple system atrophy

We studied excitatory and inhibitory amino acid binding sites autoradiographically in control and multiple system atrophy (MSA) cerebella. Within the dentate nucleus (DN) of MSA specimens, we found a significant increase in the level of GABAA, benzodiazepine, and metabotropic binding sites compared with controls. In the granule cell layer, kainate, N-methyl-D-aspartate, and GABAA binding sites were all decreased significantly in MSA specimens compared with controls. In the molecular layer of MSA cerebellum, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate binding sites were decreased significantly compared with controls. Cerebellar cortical binding site decreases are likely due to Purkinje and granule cell loss. The increase of binding site levels in DN of MSA specimens may represent receptor up-regulation reflecting loss of descending inhibitory Purkinje cell and ascending excitatory afferents to the DN.

BW619C89, a glutamate release inhibitor, protects against focal cerebral ischemic damage.

The excitatory amino acid neurotransmitter glutamate is involved in excitotoxic brain injury and neurodegeneration after cerebral ischemia. Therefore, compounds that block the release of glutamate may be useful as cerebroprotective agents. The purpose of this study was to evaluate the cerebroprotective properties of a glutamate release inhibitor, BW619C89. In the studies reported here, the effect of BW619C89 [4-amino-2-(4-methyl-1-piperazinyl)-5-(2,3,5-trichlorophenyl)pyrimidine] on neurotransmitter release (endogenous amino acids, gamma-aminobutyric acid, and acetylcholine) from slices of rat brain cerebral cortex in vitro has been determined. The neuroprotective efficacy of BW619C89 has been evaluated using the middle cerebral artery occlusion model of focal cerebral ischemia in the Fischer 344 rat. In the in vitro studies, BW619C89 inhibited veratrine- (but not potassium-) evoked release of both endogenous glutamate and aspartate from rat cerebral cortex slices with IC50 values of approximately 5 microM. BW619C89 was approximately 10-fold less potent to inhibit veratrine-evoked 3H-gamma-aminobutyric acid release (IC50 = 51 microM), fourfold less potent to inhibit 3H-acetylcholine release (IC50 = 21 microM), and at 10 microM had only weak activity at excitatory amino acid (N-methyl-D-aspartate, kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) binding sites. When administered intravenously to Fischer 344 rats 5 minutes after permanent middle cerebral artery occlusion, BW619C89 produced marked reductions of both total (cortex and basal ganglia) and cortical infarct volumes. Cortical infarct size was reduced by 20% at a dose of BW619C89 of 5 mg/kg (n = 6, not significant); 43% at 10 mg/kg (n = 8, P < .01); 59% at 20 mg/kg (n = 8, P < .001); 61% at 30 mg/kg (n = 8, P < .001), and 53% at 40 mg/kg (n = 8, P < .001). BW619C89 at doses of 20 and 30 mg/kg also significantly reduced noncortical (basal ganglia) infarct volumes, demonstrating that a proportion of this tissue also appears to be salvageable. Behavioral effects observed were dose related, generally minor, and at doses of 20 mg/kg IV and above consisted of body tremor and mild ataxia lasting approximately 2 hours. These results suggest that glutamate release inhibitors such as BW619C89 may provide an alternative to excitatory amino acid receptor antagonists in the treatment of focal cerebral ischemia and stroke.

Glutamate Receptor Binding Sites in MPTP-Treated Mice

Changes in excitatory amino acid (EAA) neurotransmission are thought to play an important role in the development of parkinsonian symptoms. We examined EAA receptor binding sites in substantia nigra, striatum, globus pallidus, and cortex at 2 weeks and 2 months after MPTP (1-methyl-4-phenyl-1,2,3,6-tetra-hydroxypyridine) injection in C57bl6 mice. At 2 weeks striatal dopamine content in MPTP-treated mice was reduced to 7% of control and N-methyl-D-aspartate (NMDA)-sensitive [3H]glutamate and [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) binding sites were decreased in substantia nigra to 57 and 76% of control, respectively. In globus pallidus only [3H]AMPA binding sites were decreased to 80% of control; no significant changes were found in striatum or cortex. [3H]Kainate binding sites remained unchanged. At 2 months striatal dopamine content was reduced to 31% and no changes in EAA binding sites could be detected in any of the structures examined. [3H]Mazindol binding to striatal monoamine-uptake sites was decreased to 17% of control at 2 weeks versus 37% at 2 months. Our data indicate that modulation of NMDA and AMPA binding sites in substantia nigra and globus pallidus, the major projection areas of the subthalamic nucleus, takes place only after severe impairment of the nigrostriatal system.

Localization of striatal excitatory amino acid binding site subtypes to striatonigral projection neurons

Quantitative autoradiography was used to examine the cellular localization of excitatory amino acid binding sites in the striatum following selective lesion of striatonigral projection neurons. Degeneration of striatonigral neurons was induced unilaterally by injection of the suicide transport toxin, volkensin, into the left substantia nigra. Twelve days following nigral volkensin injection there was a reduction of all excitatory amino acid binding site subtypes in the striatum ipsilateral to the injected nigra. The reduction in N-methyl-D-aspartate (NMDA) binding sites was significantly greater than the loss of D,L-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA), kainate and metabotropic binding. These results indicate that there are NMDA, AMPA, metabotropic and kainate binding sites on striatonigral projection neurons and suggest that the NMDA subtype may be selectively enriched on striatonigral neurons.

Excitatory amino acid binding sites in the trigeminal principal sensory and spinal trigeminal nuclei of the rat

Quantitative autoradiography was used to examine the density and distribution of excitatory amino acid (EAA) binding site subtypes in the principal sensory and spinal trigeminal nuclei of the rat trigeminal complex. The highest densities of N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), kainate and metabotropic receptors were found in the superficial laminae (I and II) of subnucleus caudalis, a region known to be densely innervated by primary afferent nociceptive terminals. Lower densities of EAA binding sites were observed in spinal subnuclei interpolaris and oralis and within the principal sensory nucleus. These results are consistent with the hypothesis that EAAs are involved in primary afferent nociceptive neurotransmission.

Adrenal hormone effects on hippocampal excitatory amino acid binding

The influence of short-term adrenalectomy or corticosterone treatment on the binding of glutamate receptor subtypes in the rat hippocampus was explored using the technique of in vitro autoradiography. Analysis of NMDA, kainate and AMPA binding in the hippocampus was conducted on the brains of control, adrenalectomized, and adrenalectomized animals given corticosterone treatment. In addition, serum corticosterone levels were determined by RIA. No striking effects of acute adrenalectomy on the distribution or density of any glutamate receptor subtype were observed in the hippocampus. Adrenalectomy had a small but significant effect on kainate binding in the stratum lucidum and stratum radiatum of CA3 in the first experiment, but no effect in follow-up experiments. Short-term treatment with stress levels of corticosterone had no effect on the binding of NMDA or kainate in any hippocampal subfield. However, a small effect of high doses of corticosterone (CORT) was observed on AMPA binding in one subregion. Although the hippocampus is a target for glucocorticoids and uses excitatory amino acids as a primary neurotransmitter, transient manipulation of adrenal hormone levels did not directly modulate excitatory amino acid receptor binding.

In vitro autoradiography of hippocampal excitatory amino acid binding in aged Fischer 344 rats: Relationship to performance on the Morris water maze.

In vitro autoradiography of hippocampal excitatory amino acid binding in aged Fischer 344 rats: Relationship to performance on the Morris water maze.

Excitatory amino acid binding sites in the basal ganglia of the rat: A quantitative autoradiographic study

Quantitative receptor autoradiography was used to determine the distribution of excitatory amino acid binding sites in the basal ganglia of rat brain. alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid, N-methyl-D-aspartate, kainate, quisqualate-sensitive metabotropic and non-N-methyl-D-aspartate, non-kainate, non-quisqualate glutamate binding sites had their highest density in striatum, nucleus accumbens, and olfactory tubercle. Kainate binding was higher in the lateral striatum but there was no medial-lateral striatal gradient for other binding sites. N-Methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding sites were most dense in the nucleus accumbens and olfactory tubercle. There was no dorsal-ventral gradient within the striatal complex for the other binding sites. Other regions of the basal ganglia had lower densities of ligand binding. To compare binding site density within non-striatal regions, binding for each ligand was normalized to the striatal binding density. When compared to the striatal complex, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and metabotropic binding sites had higher relative density in the globus pallidus, ventral pallidum, and subthalamic nucleus than other binding sites. Metabotropic binding also had a high relative density in the substantia nigra. Non-N-methyl-D-aspartate, non-kainate, non-quisqualate glutamate binding sites had a high relative density in globus pallidus, ventral pallidum, and substantia nigra. N-Methyl-D-aspartate binding sites had a low relative density in pallidum, subthalamic nucleus, substantia nigra and ventral tegmental area. Our data indicate heterogeneous distribution of excitatory amino acid binding sites within rat basal ganglia and suggest that the character of excitatory amino acid-mediated neurotransmission within the basal ganglia is also heterogeneous.

In vitro autoradiography of hippocampal excitatory amino acid binding in aged Fischer 344 rats: relationship to performance on the Morris water maze.

Young and aged Fischer 344 rats were tested on the place and cue versions of the Morris water maze task. Although all of the young animals reached criterion within the 8-day testing period, the aged animals could be divided into two groups on the basis of their performance to criterion: achievers and nonachievers. Upon completion of the water maze testing, the animals were sacrificed, and their brains were processed for in vitro autoradiography of hippocampal excitatory amino acid receptors. Significant differences were found between the young and old rats in the levels of N-methyl-D-aspartate, CPP, kainate, and AMPA binding in subregions of the hippocampus. Despite the age-related decline in hippocampal glutamate receptors, no relationship was observed between the density or distribution of excitatory amino acid receptors and performance on the water maze task in the aged rats.

Transient postnatal increases in excitatory amino acid binding sites in rat ventral mesencephalon

The developmental profile of three sub-types of excitatory amino acid (EAA) binding sites was determined in the ventral mesencephalon and the striatum of rats from prenatal day 19 to adult (3 months) using membrane binding assays. In the ventral mesencephalon, there was a transient increase of EAA receptor binding sites beyond adult levels, which peaked at postnatal day 7 (P7) for [3H]glutamate binding to NMDA receptors and at P14 for [3H]AMPA and [3H]kainate binding. In the striatum, [3H]glutamate/NMDA and [3H]kainate binding reached adult levels during the early postnatal period, stabilizing at this level with no transient overexpression beyond adult levels. [3H]AMPA binding also showed an increase above adult levels at P14 in the striatum. These results raise the possibility that the transient overexpression of EAA receptors in the ventral mesencephalon may affect the developmental fate of dopaminergic and other neurons in this region.

Excitatory amino acid binding sites in the caudate nucleus and frontal cortex of huntington's disease

Huntington's disease is a dominantly inherited, progressive neurodegenerative disorder causing marked pathology in the basal ganglia. The pathophysiology of the selective neuronal death is as yet unknown, but evidence suggests that the neurotoxicity may result from endogenous substances acting at excitatory amino acid receptors. Previous data have shown a selective decrease in binding to one class of glutamate receptors, the N-methyl-D-aspartate (NMDA) receptor in the putamen of Huntington's disease. The present study was undertaken to determine the relative density of binding to all of the currently defined subpopulations of excitatory amino acid receptors in the caudate nuclei and frontal cortex of patients with Huntington's disease and of control subjects, using quantitative in vitro autoradiography. NMDA, MK-801, glycine, kainate, and alpha-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptor binding were all decreased to a similar extent (50-60%). Binding to the metabotropic quisqualate receptor and to the non-NMDA, nonkainate, nonquisqualate (NNKQ) site was decreased nonsignificantly by 31% and 26%, respectively. Autoradiograms of NMDA, MK-801, AMPA, kainate, metabotropic, and NNKQ receptors in caudates revealed an inhomogeneous pattern of binding that is different from the binding pattern seen in control caudates. Binding to all receptor subtypes was the same in the frontal cortex from Huntington's disease patients and control subjects. The data suggest that no single excitatory amino acid receptor is selectively decreased in the caudate of Huntington's disease.

Excitatory and inhibitory amino acid binding sites in human dentate nucleus

Autoradiography of excitatory and inhibitory amino acid binding sites in human dentate nuclei indicated virtually no binding to N-methyl-D-aspartate (NMDA) or gamma-aminobutyric acidB (GABAB) binding sites, and a low density of kainate binding sites. alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid, metabotropic-quisqualate, benzodiazepine, and gamma-aminobutyric acidA (GABAA) binding sites were present in moderate abundance. Our NMDA results differ from those found previously in rodents. GABAA receptors are probably the primary mediators of inhibitory neurotransmission and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and metabotropic-quisqualate receptors are probably the primary mediators of excitatory neurotransmission within the human deep cerebellar nuclei.