Neuroscience
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Comparative Study
Characterization and regional distribution of strychnine-insensitive [3H]glycine binding sites in rat brain by quantitative receptor autoradiography.
Recent evidence suggests that a strychnine-insensitive glycine modulatory site is associated with the N-methyl-D-aspartate receptor-channel complex. A quantitative autoradiographic method was used to characterize the pharmacological specificity and anatomical distribution of strychnine-insensitive [3H]glycine binding sites in rat brain. [3H]Glycine binding was specific, saturable, reversible, pH and temperature-sensitive and of high affinity. [3H]Glycine interacted with a single population of sites having a KD of approximately 200 nM and a maximum density of 6.2 pmol/mg protein (stratum radiatum, CA1). Binding exhibited a pharmacological profile similar to the physiologically defined strychnine-insensitive glycine modulatory site. ⋯ The distribution of strychnine-insensitive [3H]glycine binding was heterogeneous with the following rank order of binding densities: hippocampus greater than cerebral cortex greater than caudate-putamen greater than or equal to thalamus greater than cerebellum greater than brain stem. This distribution of binding was correlated with N-methyl-D-aspartate-sensitive [3H]glutamate binding (r2 = 0.77; P less than 0.001; Pearson product-moment) and [3H]thienylcyclohexylpiperidine binding (r2 = 0.72; P less than 0.001). These observations are consistent with the hypothesis that the strychnine-insensitive glycine binding site is closely associated with the N-methyl-D-aspartate receptor-channel complex.(ABSTRACT TRUNCATED AT 400 WORDS)
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Comparative Study
Dopamine high-affinity transport site topography in rat brain: major differences between dorsal and ventral striatum.
Investigations were conducted to determine the topography of the high-affinity dopamine uptake process within the rat striatum. [3H]Dopamine uptake into crude synaptosomes prepared from micropunch samples was found to be two- to three-fold higher in dorsal caudate-putamen relative to nucleus accumbens septi. In contrast, the concentrations of dopamine in the two regions were equivalent. The recognition site associated with high-affinity dopamine uptake was labeled using [3H]mazindol, and the binding of this ligand was also found to be two- to three-fold higher in homogenates from dorsal caudate-putamen samples relative to nucleus accumbens septi. ⋯ Further autoradiographic studies revealed less striatal heterogeneity in the pattern of binding of [3H]ketanserin, another radioligand associated with the striatal dopaminergic innervation but not linked to the dopamine uptake process of the plasma membrane. The findings suggest that the dopaminergic fibers of the ventral striatum, especially the medial nucleus accumbens septi, may be relatively lacking in their capacity for dopamine uptake following its release. This organization may result in regional differences in the time-course of of extraneuronal dopamine following transmitter release and may render the dopamine-containing terminals of the ventral striatum less susceptible to the degenerative influences of neurotoxins that are incorporated by the high-affinity dopamine uptake process.
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[3H]GABA quantitative autoradiography was used to examine the binding kinetics and regional distribution of GABAB receptors in rat brain. The regional distribution was compared to that of GABAA receptors. At 4 degrees C, [3H]GABA binding to GABAB receptors reached equilibrium within 45 min. ⋯ Areas high in GABAB binding included the medial and lateral geniculates, the superior colliculus and certain amygdaloid nuclei. Binding to white matter tracts and ventricles was negligible. The distribution of GABAB receptors was in agreement with previously postulated sites of action of baclofen.
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Effects of senna on the myenteric plexus of the colon were investigated in view of earlier reports that this anthraquinone cathartic depletes the plexus of its intrinsic neurons. Rats and mice were given purgative doses of sennosides in their drinking water for 4 and 5 months, respectively. Body growth was reduced, and the weight of the colon with its contents was increased relative to the weight of the whole body in the treated animals. ⋯ Treatment with senna was not associated with absence of neuronal somata or fibres stainable with any of the antisera in either species. Thus, there was no evidence of toxic destruction of any identifiable population of neurons that might have been too small to affect the total counts. We conclude that senna does not kill myenteric neurons in the colon of the rat or mouse.
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N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) is a potent and highly selective neurotoxin which induces degeneration of noradrenergic axons. The effects of DSP-4 vary considerably in different brain regions: the drug produces nearly complete depletion of noradrenaline in neocortex, hippocampus, cerebellum and spinal cord, but only partial depletion in hypothalamus and brainstem. In this study we have employed an immunohistochemical method to assess the neurotoxic effects of DSP-4 on the structural integrity of central noradrenergic neurons in the rat, and to identify those noradrenergic axons that remain in the central nervous system 2-4 weeks after DSP-4 treatment. ⋯ This study provides the first direct evidence that DSP-4 destroys noradrenergic axon terminals from the locus coeruleus, but not those from non-locus coeruleus neurons. This profound differential sensitivity of noradrenergic axons to DSP-4 is matched by distinct differences in their morphology and their topographic projections. The results support the view that locus coeruleus and non-locus coeruleus noradrenergic neurons constitute two separate subsystems, which differ not only in their projections but also with respect to the pharmacological properties of their axon terminals.