Toxic effect of MDMA on brain serotonin neurons.
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Brain↗
Biomedical subjects
K L Jansen
Publications and source records attributed to K L Jansen.
Ecstasy (MDMA) dependence.
Methylenedioxymethamphetamine (MDMA) is generally described as non-addictive. However, this report describes three cases in which criteria for dependence were met. A wider understanding that MDMA can be addictive in rare cases is important as very heavy use may cause lasting neuronal changes. This risk could be reduced with effective identification and treatment of dependent persons. In one case dependence was linked with self-medication of post-traumatic stress disorder (PTSD).
Adult↗
Loss of sigma binding sites in the CA1 area of the anterior hippocampus in Alzheimer's disease correlates with CA1 pyramidal cell loss.
The densities of [3H]1,3-di-o-tolylguanidine ([3H]DTG) binding to sigma binding sites in the CA1 stratum pyramidale region in 7 hippocampi affected by Alzheimer's disease, were compared with densities in 7 normal hippocampi. There was an average reduction of 26% in [3H]DTG binding in this area, which was correlated with an average 29% pyramidal cell loss in the same region. These results are consistent with experiments in animals indicating that sigma binding sites are preferentially associated with the somata of large cells.
Aged↗
Non-medical use of ketamine.
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Dissociative Disorders↗
sigma receptors in rat brain and testes show similar reductions in response to chronic haloperidol.
The effect of haloperidol upon [3H]1,3-di-o-tolylguanidine ([3H]DTG) binding sites was assessed in rat brain and testes. An acute injection (10 mg/kg), in rats culled 2 h later, changed Kd values from 18 +/- 2 to 108 +/- 26 nM (brain) and 14 +/- 1 to 116 +/- 35 nM (testes), with unchanged Bmax values. Rats were injected with 4 mg/kg per day for 7, 14 and 21 days and culled 4 days after the last injection. By day 21, there was an average fall in Bmax for brain of 30% and for testes of 38%. Kd values remained unchanged. Thus peripheral and central [3H]DTG binding sites were reduced by chronic haloperidol in a similar way.
Animals↗
Distribution of excitatory and inhibitory amino acid, sigma, monoamine, catecholamine, acetylcholine, opioid, neurotensin, substance P, adenosine and neuropeptide Y receptors in human motor and somatosensory cortex.
Autoradiography was used to visualise N-methyl-D-aspartate, phencyclidine, strychnine-insensitive glycine, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, kainic acid, benzodiazepine, gamma-aminobutyric acid type A, sigma, serotonergic, dopaminergic, alpha 2-adrenergic, beta-adrenergic, muscarinic cholinergic, nicotinic, opioid, neurotensin, substance P, adenosine A1 and neuropeptide Y receptors in the human primary motor (Brodmann's area 4) and somatosensory cortex (Brodmann's areas 3, 2 and 1). With the exception of serotonin type 2 receptors, all receptor types examined had a similar distribution in area 4 which showed little dependence on the underlying distribution of cell somata, often continuing unaltered through the somatosensory cortex despite marked cytoarchitectural changes. The highest densities occurred in the outer (most superficial) 30-40% of the cortical grey matter, followed by a band of relatively low binding and then moderate levels in the inner (deeper) region. In many instances, an additional band of dense binding could be discerned in the region of laminae IV/Va running unbroken through both gyri. The distribution of most receptor types in the somatosensory cortex also followed this pattern, except for opioid and kainic acid receptors which showed higher levels in the inner rather than the outer third of this region. At the edge of area 4, a change occurred such that a high density outer band appeared, giving these receptor types the same pattern in area 4 as the majority. Serotonin type 2 receptor levels were quite low in the outermost region of area 4, although the pattern was otherwise similar to that of the other receptors. Thus, with the exception of serotonin receptors, the similarity in many binding site distributions recently noted in area 4 of the rhesus monkey also tends to occur in the human area 4, to the extent that 2 ligands will reverse their usual cortical binding pattern to conform with the common area 4 pattern.
Autoradiography↗
Autoradiographic distribution of sigma receptors in human neocortex, hippocampus, basal ganglia, cerebellum, pineal and pituitary glands.
Autoradiographic distributions of [3H]1,3-di-O-tolylguanidine, [3H]DTG, binding to sigma (sigma) receptors were studied in key human brain regions. High densities occurred in the substantia nigra pars compacta and cerebellum. Pineal and pituitary levels were moderate. In neocortex, binding was high in laminae II-IVA and much lower in the midzone. Moderate binding occurred over hippocampal dentate granular cells and in the striatum. These results differ from those reported for the rodent.
Adult↗
Autoradiographic visualisation of [3H]DTG binding to sigma receptors, [3H]TCP binding sites, and L-[3H]glutamate binding to NMDA receptors in human cerebellum.
The autoradiographic distributions of [3H]1,3-di-ortho-tolyguanidine ([3H]DTG), [3H]1-[1-(2-thienyl) cyclohexyl] piperidine ([3H]TCP) and L-[3H]glutamate were studied in the human cerebellum. [3H]DTG is a selective label for the sigma receptor, while L-[3H]glutamate binding was carried out under conditions selective for the N-methyl-D-aspartate (NMDA) receptor. [3H]TCP binding sites and sigma receptors showed marked enrichment in the Purkinje cell layer, while L-[3H]glutamate-labelled NMDA receptors showed virtually no binding in the Purkinje cell layer. The results confirm the existence of [3H]TCP binding sites which are not linked to NMDA receptors in the human cerebellum, having a distribution which is more similar to that of the haloperidol-sensitive sigma receptor.
Autoradiography↗
Transcendental explanations and near-death experience.
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Cognition↗
NMDA and kainic acid receptors have a complementary distribution to AMPA receptors in the human cerebellum.
The distributions of N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-S-methyl-4-isoxazole propionic acid (AMPA) and kainic acid (KA) receptors were determined in the human cerebellum using autoradiography. In contrast to the cerebral cortex, where KA receptors have a complementary distribution to NMDA and AMPA receptors, AMPA receptors were concentrated in the cerebellar molecular layer while NMDA and KA receptors were concentrated in the granular layer.
Aged↗
MK-801, an antagonist of NMDA receptors, inhibits injury-induced c-fos protein accumulation in rat brain.
Unilateral lesions of the rat hippocampus produced by needle insertion lead to ipsilateral accumulation of c-fos protein in dentate granule cells and neurons in the piriform cortex, as well as in glial-like cells in the corpus callosum and in ependymal cells lining the lateral ventricle adjacent to the lesion site. C-fos protein was detected immunocytochemically using two different antibodies in formalin-fixed brain sections. The N-methyl-D-aspartate (NMDA) antagonist MK-801 produced a dose- and time-dependent inhibition of c-fos protein accumulation in dentate granule cells and in neurons in the piriform cortex, but did not affect glial or ependymal c-fos protein accumulation. MK-801 at 4 mg/kg injected two hours before lesion inhibited c-fos accumulation. Thus, c-fos protein accumulation in hippocampal neurons and in neurons in the piriform cortex induced after traumatic brain injury involves activation of NMDA receptors.
Animals↗
Sigma receptors are highly concentrated in the rat pineal gland.
The distribution of sigma (sigma) receptors in the rat brain was studied with autoradiography using [3H]1,3-di-ortho-tolyl-guanidine ([3H]DTG) as a ligand. The highest concentration of sigma receptors was seen in the pineal gland, an area which has not been previously studied. This result is of interest as both sigma receptors and the pineal gland have recently been shown to play a role not only in the nervous system but also in the immune and endocrine systems.
Animals↗
Autoradiographic localisation of NMDA, quisqualate and kainic acid receptors in human spinal cord.
The phencyclidine (PCP) binding site of the N-methyl-D-aspartate receptor, the kainic acid (KA) receptor and the quisqualate (QA) receptor were visualised, using autoradiography in the human spinal cord and the distributions compared with that of benzodiazepine (BDZ) receptors and substance P (SP). All of the receptor types, and SP, were concentrated in lamina II of the dorsal horn, consistent with physiological data indicating that glutamate is a neurotransmitter of primary afferent terminals in the spinal cord.
Adult↗
Alzheimer's disease: changes in hippocampal N-methyl-D-aspartate, quisqualate, neurotensin, adenosine, benzodiazepine, serotonin and opioid receptors--an autoradiographic study.
The following receptors were assessed post-mortem in the hippocampi (anterior region) of eight patients with Alzheimer's disease and nine age-matched controls, using autoradiography: N-methyl-D-aspartate (including glutamate, phencyclidine and glycine binding sites), quisqualate, kainic acid, adenosine A1, benzodiazepine, serotonin (1 and 2), muscarinic cholinergic, beta-adrenergic, neurotensin and opioid receptors. In CA1 there were significant parallel losses of binding to the three N-methyl-D-aspartate-linked sites (average reduction 46%) and also losses of quisqualate (38%) and serotonin2 (58%) receptor binding, with a 47% loss of binding to A1 sites. Binding to all of these receptors was also reduced in CA3 (except binding to A1 sites which was normal) but only the serotonin2 receptor binding loss reached significance (52%). A significant reduction in binding was also observed in the entorhinal area to the N-methyl-D-aspartate receptor-linked sites (average reduction = 39%), benzodiazepine (40%) and serotonin2 receptors (45%), and there was a loss of binding to neurotensin (57%) and opioid receptors (42%). Significant reductions in the dentate gyrus molecular layer were seen for serotonin2 receptors (44%), and binding to opioid (44%) and A1 receptors (46%). Levels of ligand binding to muscarinic cholinergic, serotonin1, beta-adrenergic and kainic acid receptors were not significantly different from control values in any of the four areas examined. These results provide support for observations of selective receptor changes in Alzheimer's disease involving a broad range of receptor types which encompass both excitatory amino acid and other receptors (notably serotonin2, A1, benzodiazepine, neurotensin and opioid receptors). The implications of the pattern of receptor changes for the suggestion that excitotoxicity plays a role in the disease are discussed, as is the possible contribution of the receptor changes to the symptomatology of Alzheimer's disease.
Aged↗
GABA, GABA receptors and benzodiazepine receptors in the human spinal cord: an autoradiographic and immunohistochemical study at the light and electron microscopic levels.
The regional, cellular and subcellular distribution of GABA, GABA receptors and benzodiazepine receptors was investigated by light and electron microscopy in the human lumbar spinal cord taken post-mortem from eight cases aged 20-76 years. Firstly, the regional distribution of GABA receptors and benzodiazepine receptors was studied using autoradiography following in vitro labelling of cryostat sections with tritiated ligands. This was followed by a detailed study of the cellular and subcellular distribution and localization of GABA and benzodiazepine/GABAA receptors by light and electron microscopy using immunohistochemical techniques with monoclonal antibodies to GABA and to the alpha and beta subunits of the benzodiazepine/GABAA receptor complex. The results showed a close correspondence in the regional distributions of GABA, GABA (GABAA and GABAB) receptors and benzodiazepine receptors. The highest density of GABA-like immunoreactivity, GABA receptors and benzodiazepine receptors was localized as a dense band within lamina II of the dorsal horn (especially inner lamina II) with moderately high densities in laminae I and III. The remaining laminae of the spinal gray matter showed much lower levels of labelling. A close correspondence was also seen in the distribution of GABA-like immunoreactivity and of benzodiazepine/GABAA receptor immunoreactivity at the cellular and subcellular levels. At the cellular level, the greatest number of GABA-immunoreactive cells was found in lamina II; they comprised small, round to oval cells and, on the basis of soma size, shape, orientation and dendromorphology, they corresponded to previously described islet and filamentous cells. Benzodiazepine/GABAA receptor immunoreactivity was also localized on the same cell types in lamina II. At the subcellular level in lamina II, GABA-immunoreactive axon terminals mainly established axodendritic synaptic contacts. Small numbers of GABA-immunoreactive axon terminals appear to form possible axo-axonic contacts in complex synaptic arrays. Benzodiazepine/GABAA receptors were localized within the same types of synaptic complexes in which GABA-immunoreactive axon terminals were found. In these synaptic complexes, benzodiazepine/GABAA receptor immunoreactivity was associated with presynaptic and postsynaptic membranes and on apparent non-synaptic membranes. These results show a high concentration of GABA, GABA receptors and benzodiazepine receptors in lamina II of the dorsal horn of the human spinal cord and suggest a possible role for GABA in spinal sensory functions.
Autoradiography↗
Neuroscience and the near-death experience: roles for the NMSA-PCP receptor, the sigma receptor and the endopsychosins.
The Near-Death Experience (NDE) is a dissociative mental state with characteristic features. These can be reproduced by ketamine which acts at sigma sites and blocks N-methyl-D-aspartate (NMDA) linked phencyclidine (PCP) receptors to reduce ischaemic damage. Endogenous ligands, alpha and beta-endopsychosin, have been detected for these receptors which suggests an explanation for some NDE's: the endopsychosins may be released in abnormal quantity to protect neurons from ischaemic and other excitotoxic damage, and the NDE is a side effect on consciousness with important psychological functions.
Consciousness↗
Ketamine--can chronic use impair memory?
Ketamine, a congener of phencyclidine (PCP), can produce a range of psychological effects which have led to its nonmedical use. Recent discoveries concerning the effects of ketamine and similar substances in the brain suggest that they may interfere with memory processes when given acutely and may affect synaptic plasticity when given chronically in high doses in certain animal models. It is thus of interest to examine the consequences, if any, of chronic use in humans. A case is here presented of long-term, high-dose ketamine use, in which the user described impaired recall and attention, and a subtle visual anomaly persisting after cessation of the habit. This history is considered in the context of other relevant studies.
Attention↗
[3H]glycine binding sites, NMDA and PCP receptors have similar distributions in the human hippocampus: an autoradiographic study.
The distribution of [3H]glycine binding sites was compared with that of N-methyl-D-aspartate (NMDA) receptors labelled with L-[3H]glutamate, and with that of phencyclidine (PCP) receptors labelled with [3H]1-(1-(2-thienyl)-cyclohexyl)piperidine ([3H]TCP) in sections from 7 normal human hippocampi. The results indicate that strychnine-insensitive glycine binding sites are present in high concentrations in CA1 and the molecular layer of the dentate gyrus. This distribution is very similar to the distributions of NMDA and PCP receptors in the human hippocampus.
Adult↗