bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative autoradiography of Gpp(NH)p sensitive and insensitive [3H]quinpirole binding sites in the rat brain
Authors: Gehlert Donald R. 
Published: December 2004

AbstractRecent advances in the cloning of dopamine receptor subtypes have resulted in the detection of at least 5 genetically distinct subtypes of the dopamine receptor. The dopaminergic agonist, quinpirole, has relatively high affinity for the cloned D‐2, D‐3, and D‐4 receptor subtypes. The D‐3 receptor is unique within these 3 subtypes in that it does not appear to have sensitivity to guanine nucleotides. In order to localize the brain regions containing these subtypes of the dopamine receptor, the distribution of [3H]quinpirole binding sites in the rat brain was mapped by autoradiography. Labelling in the absence and presence of the nonhydrolyzable GTP analog, guanylyl‐5′‐imidodiphosphate (Gpp(NH)p) allowed differentiation between the high affinity agonist conformation of the D‐2 receptor and the D‐3 receptor. The highest densities of [3H]quinpirole binding were found in the caudate‐putamen, nucleus accumbens, islands of Calleja, and olfactory tubercle which is consistent with the distribution of dopamine receptors seen with “classical D‐2” receptor agonist and antagonist radioligands. In the presence of 10 μM Gpp(NH)p, binding was reduced in all these areas with the exception of the islands of Calleja. Additional areas which exhibited no change in binding when incubated with Gpp(NH)p included the nodulus and floculus of the cerebellum. Several areas exhibited a partial reduction in binding including the glomerular layer of the olfactory bulb, nucleus accumbens, and the superior colliculus. The distribution of these subtypes is consistent with the distribution of mRNA for the D‐2 and D‐3 receptor in the brain. Therefore, [3H]quinpirole binds to the high affinity agonist conformation of the D‐2 and the D‐3 receptor. © 1993 Wiley‐Liss, Inc.
In vivo imaging of monoaminergic nerve terminals in normal and MPTP‐lesioned primate brain using positron emission tomography (PET) and [11C]tetrabenazine
Authors: DaSilva Jean N. , Kilbourn Michael R. , Domino Edward F. 
Published: December 2004

AbstractThe first successful in vivo imaging of monoamine vesicular transporters in the living primate brain is described, using [11C]tetrabenazine ([11C]TBZ) and Positron Emission Tomography (PET). Radioligand uptake into brain is rapid, and at short time periods (10‐30 minutes) the higher uptake and retention of the radiotracer in the more densely dopaminergic innervated striatum is clearly visualized. Specific binding in striatum can be entirely blocked with co‐administration of a pharmacological dose (1 mg/kg i. v.) of tetrabenazine. In a unilaterally MPTP‐lesioned monkey, specific binding of radioligand was absent in the striatum on the lesioned side, with no effect on radiotracer distribution in the cortex, cerebellum or contralateral striatum. PET imaging with [11C]TBZ provides a new approach to the in vivo study of monoaminergic neurons and their loss in neurodegenerative diseases. © 1993 Wiley‐Liss, Inc.
Nucleus basalis stimulation facilitates thalamocortical synaptic transmission in the rat auditory cortex
Authors: Metherate Raju , Ashe John H. 
Published: December 2004

AbstractNucleus basalis (NB) neurons are a primary source of neocortical acetylcholine (ACh) and likely contribute to mechanisms of neocortical activation. However, the functions of neocortical activation and its cholinergic component remain unclear. To identify functional consequences of NB activity, we have studied the effects of NB stimulation on thalamocortical transmission. Here we report that tetanic NB stimulation facilitated field potentials, single neuron discharges, and monosynaptic excitatory postsynaptic potentials (EPSPs) elicited in middle to deep cortical layers of the rat auditory cortex following stimulation of the auditory thalamus (medial geniculate, MG). NB stimulation produced a twofold increase in the slope and amplitude of the evoked short‐latency (onset 3.0 ± 0.13 ms, peak 6.3 ± 0.21 ms), negative‐polarity cortical field potential and increased the probability and synchrony of MG‐evoked unit discharges, without altering the preceding fiber volley. Intracortical application of atropine blocked the NB‐mediated facilitation of field potentials, indicating action of ACh at cortical muscarinic receptors. Intracellular recordings revealed that the short‐latency cortical field potential coincided with a short‐latency EPSP (onset 3.3 ± 0.20 ms, peak 5.6 ± 0.47 ms). NB stimulation decreased the onset and peak latencies of the EPSP by about 20% and increased its amplitude by 26%. NB stimulation also produced slow membrane depolarization and sometimes reduced a long‐lasting IPSP that followed the EPSP. The combined effects of NB stimulation served to increase cortical excitability and facilitate the ability of the EPSP to elicit action potentials. Taken together, these data indicate that NB cholinergic neurons can modify neocortical functions by facilitating thalamocortical synaptic transmission. © 1993 Wiley‐Liss, Inc.
Neurochemical correlates of behavioral sensitization following repeated apomorphine treatment: Assessment of the role of D1 dopamine receptor stimulation
Authors: Rowlett James K. , Mattingly Bruce A. , Bardo Michael T. 
Published: December 2004

AbstractPrevious research has revealed a role of repeated D1 dopamine receptor stimulation in the development of behavioral sensitization to the D1/D2 agonist apomorphine. The present experiments assessed the role of repeated D1 receptor stimulation in neurochemical changes accompanying locomotor sensitization to apomorphine. To assess direct effects of D1 stimulation on dopamine synthesis, rats were injected with the D1 agonist SKF 38393 (8 mg/kg), followed by an injection with the 3,4‐dihydroxyphenylalanine (DOPA) decarboxylase inhibitor, NSD‐1015. DOPA accumulation, assessed in striatal, nucleus accumbens‐olfactory tubercle (NAOT), and ventral mesencephalon (VM) tissue samples, was not affected by acute SKF 38393. In the second experiment, rats were treated with 10 daily injections of vehicle, apomorphine (5 mg/kg) or the D1 agonist SKF 38393 (8 or 16 mg/kg). Daily measures of locomotor activity demonstrated a progressive increase in the apomorphine‐treated rats, but not the SKF 38393‐treated rats, across the 10 days. On day 11, all rats were injected with NSD‐1015 for measurement of DOPA accumulation. Dopamine synthesis was enhanced in the striatum after repeated apomorphine treatment. In contrast, repeated SKF 38393 treatment resulted in either a small decrease or no change in DOPA accumulation in the different brain regions (striatum, NAOT, VM). In the third experiment, tissue levels of dopamine, 3,4‐dihydroxyphenylacetic acid (DOPAC) and [3H]SCH 23390 binding to D1 receptors were measured in rats treated with 10 daily injections of vehicle, apomorphine (5 mg/kg), or SKF 38393 (16 mg/kg). In the striatum and NAOT, none of the repeated drug treatments had an effect on DOPAC or dopamine levels. In the VM, DOPAC levels were enhanced following repeated apomorphine, but not repeated SKF 38393, whereas dopamine levels were not affected by either drug treatment. D1 binding was not altered by the repeated drug treatments. Since repeated D1 stimulation by SKF 38393 did not produce the same alterations in dopamine synthesis and DOPAC levels as repeated apomorphine, the neurochemical effects accompanying locomotor sensitization to apomorphine probably are not mediated by D1 receptors. © 1993 Wiley‐Liss, Inc.
Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers
Authors: Volkow Nora D. , Fowler Joanna S. , Wang Gene‐Jack , Hitzemann Robert , Logan Jean , Schlyer David J. , Dewey Stephen L. , Wolf Alfred P. 
Published: December 2004

AbstractDecreased dopaminergic function has been postulated to underlie cocaine addiction. To examine the possibility that dysfunction of brain regions subserved by the dopamine system could promote cocaine self‐administration, positron emission tomography and a dual‐tracer approach was used to examine dopamine D2 receptor availability and regional brain glucose metabolism in cocaine abusers. When compared to normal controls, cocaine abusers showed significant decreases in dopamine D2 receptor availability which persisted 3‐4 months after detoxification. Decreases in dopamine D2 receptor availability were associated with decreased metabolism in several regions of the frontal of these brain areas which are involved in the channeling of drive and affect could lead to loss of control resulting in compulsive drug‐taking behavior. © 1993 Wiley‐Liss, Inc.
Alterations in striatal and extrastriatal D‐1 and D‐2 dopamine receptors in the MPTP‐treated common marmoset: An autoradiographic study
Authors: Gnanalingham Kanna K. , Smith Lance A. , Hunter A. Jackie , Jenner Peter , Marsden C. David 
Published: December 2004

AbstractIn adult common marmosets (Callithrix jacchus), MPTP (1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine) treatment induced almost total depletion of cells in the substantia nigra pars compacts (SNc) but partial cell loss in the ventral tegmental area (VTA). There was severe depletion of [3H]‐mazindol binding to dopamine (DA) uptake sites in the caudate, putamen, and SNc. The loss of [3H]‐mazindol binding in the nucleus accumbens (NAc) and olfactory tubercle (OT) was less marked. [3H]‐mazindol binding in the body of caudate nucleus showed a small but significant recovery with increasing post‐lesion survival times.The specific binding of [3H]‐SCH 23390 to D‐1 DA receptor sites was increased after MPTP treatment in all subregions of both caudate and putamen but was unaltered in the NAc and OT. Substantia nigra pars reticulata (SNr), frontal cortex, and medial segment of globus pallidus (GPm) all demonstrated moderate levels of [3H]‐SCH 23390 binding in control animals, which were unaffected by MPTP treatment. Specific [3H]‐spiperone binding to D‐2 DA receptor sites was not altered by MPTP treatment in the subregions of caudate‐putamen. Moderate levels of [3H]‐spiperone binding were observed in control animals in the NAc, OT, SNc, and the lateral segment of globus pallidus (GPl). [3H]‐spiperone binding in the SNc and OT was partially decreased in MPTP‐treated animals. The changes in specific [3H]‐spiperone and [3H]‐SCH 23390 binding induced by MPTP‐treatment did not alter with post‐lesion survival times.These results demonstrate that MPTP treatment causes greater dopaminergic denervation of the caudate‐putamen than in NAc/OT. This resulted in an increase in postsynaptic D‐1 DA receptor sites in the caudate‐putamen but not in the NAc/OT. Also, there appeared to be loss of presynaptic D‐2 DA receptic sites in the SNc and OT. In the caudate‐putamen, the loss of presynaptic D‐2 DA receptor sites may have masked postsynaptic D‐2 DA receptor upregulation. © 1993 Wiley‐Liss, Inc.
Low density of dopamine D4 receptors in Parkinson's, schizophrenia, and control brain striata
Authors: Seeman Philip , Guan Hong‐Chang , Van Tol Hubert H. M. , Niznik Hyman B. 
Published: December 2004

AbstractThe purpose of this study was to determine whether dopamine D4 receptors could be detected in the human brain striatum by means of an indirect ligand‐binding method, because no dopamine D4 receptor‐selective ligand presently exists. The antipsychotic clozapine is more selective for the dopamine D4 receptor than for other dopamine receptors. Although most antipsychotic drugs act in the striatum to elicit Parkinson‐like side‐effects, clozapine is atypical in that it does not produce Parkinsonism. To understand this atypical action of clozapine, it would be helpful to know whether the presumed target for clozapine, the dopamine D4 receptor, is or is not present in the human striatum. We measured dopamine D4 receptors indirectly, using [3H]emonaprideEmonapride (or YM‐09151‐2; eis‐N‐[(2RS,3RS)‐l‐benzyl‐2‐methylpyrrolin‐ 3‐yll‐5‐chloro‐2‐methoxy‐4‐∼methylamino‐benzamide]) contains two asymmetric carbon atoms and is, therefore, a racemate of four enantiomers, two of which, (R,R)YM‐O9151‐2 and (S,S)YM‐09151‐2, are active with identical potency (see Refs. in Seeman et al., 1992).
and [3H]raclopride. Emonapride has a high affinity (K = 90 pM) for the dopamine D4 receptor, while raclopride has a very low affinity for this receptor (K = 240 nM); thus, any difference in the densities of these two [3H]ligands (in the absence of dopamine) could be attributed to the presence of dopamine D4 receptors. Since the binding of [3H]raclopride is sensitive to endogenous dopamine, we used Parkinson‐diseased tissue which has little dopamine. We found that the densities of the two ligands were identical in Parkinson striata, indicating a low density (<1 pmol/g) for dopamine D4 receptors in the human striatum. This low or undetectable density of dopamine D4 receptors in the striatum is consistent with other data indicating that clozapine does not have its major action in the human striatum. Thus, the atypical action of clozapine, insofar as clozapine does not elicit Parkinson side‐effects, may be based on its ability to avoid striatal dopamine D2 receptors and to target dopamine D4 receptors in non‐striatal brain regions. In schizophrenia striata the density of [3H]emonapride was almost two‐fold higher than that of [3H]raclopride. Considering that there are few dopamine D4 receptors in the human striatum, this two‐fold difference is best explained by endogenous dopamine interfering with the binding of [3H]raclopride, but not that of [3H]emonapride. © 1993 Wiley‐Liss, Inc.
Dopamine receptors labelled by PHNO
Authors: Seeman Philip , Ulpian Carla , Larsen Robert D. , Anderson Paul S. 
Published: December 2004

AbstractSince the high‐affinity state of dopamine D2 receptors may be abnormal in psychomotor diseases, it is desirable to develop a radioactive agonist to label this high‐affinity site for possible clinical diagnostic use. (+)PHNO is a selective D2 agonist used to treat Parkinson's disease. We prepared [3H](+)PHNO from allyl‐des‐propyl‐(+)PHNO. In binding to dopamine receptors in homogenates of canine brain striata, [3H](+)PHNO had a dissociation constant of 0.35 nM in the absence of NaCl, and 0.56 nM in the presence of NaCl. Dopamine agonists and antagonists inhibited the binding of [3H](+)PHNO at drug concentrations similar to those inhibiting other [3H]ligands at D2 receptors, but not similar to those acting at D4 receptors. Approximately 90% of the total [3H](+)PHNO binding was specific. Guanilylimidodiphosphate markedly inhibited [3H](+)PHNO binding, suggesting that [3H](+)PHNO was binding primarily to the high‐affinity state of dopamine D2 receptors rather than to D3 receptors. The density of the [3H](+)PHNO binding sites was equal to that of [3H]emonapride (or [3H]YM‐09151‐2), both densities of which were 1.5‐ to 2‐fold higher than that of [3H]spiperone, compatible with the idea that [3H](+)PHNO binds to monomers of D2, while [3H]spiperone binds to dimers of D2. Although [3H](+)PHNO has good selectivity and affinity for the high‐affinity state of D2, the [3H]ligand was sensitive to endogenous dopamine, since washing the tissue lowered the dissociation constant. For future in vivo labelling of D2 by an agonist, therefore, it will be essential to search for a related [3H]ligand with an even lower dissociation constant. © 1993 Wiley‐Liss, Inc.
Comparison of immunolocalization patterns for the synaptic vesicle proteins p65 and synapsin I in macaque monkey retina
Authors: Koontz Margaret A. , Hendrickson Anita E. 
Published: December 2004

AbstractThe distributions of the two synaptic vesicle proteins p65 [Matthew et al. (1981) J. Cell Biol., 91:257–269] and synapsin I [De Camilli et al. (1983) J. Cell Biol., 96:1337–1354] were compared in macaque monkey retina using pre‐embedding immunocytochemistry for both light and electron microscopy. The monoclonal antibody AB‐48 against p65 labeled ribbon‐containing synaptic terminals of cone, rod, and bipolar cells as well as many conventional synapses of amacrine cells. In contrast, a polyclonal antiserum against synapsin I (SYN I) labeled many amacrine conventional synapses but no photoreceptor or bipolar ribbon synaptic terminals. Horizontal cell pre‐ and post‐synaptic profiles in the outer plexiform layer were not labeled by either antibody. At the light microscopic level, the banding patterns in the inner plexiform layer also differed for the two antibodies, with four bands of AB‐48 immunoreactivity in sublayers S1, S2, S4, and S5 but only three bands of SYN I immunoreactivity in S1, S3, and S5. SYN I also labeled varicose fibers in both the inner nuclear layer and the outer plexiform layer that are probably processes of dopaminergic and GABAergic interplexiform cells. Varicose fibers in the ganglion cell layer were labeled by both antibodies. These results provide the first electron microscopic immunocytochemical labeling for AB‐48 and SYN I in intact retina and confirm that AB‐48 labels both ribbon and conventional synaptic terminals, whereas SYN I labels only conventional synapses. © 1993 Wiley‐Liss, Inc.
Comparison of associative and non‐associative conditioning procedures in the induction of LTD in CA1 of the hippocampus
Authors: Kerr D. Steven , Abraham Wickliffe C. 
Published: December 2004

AbstractRecent reports have indicated that weak activity in a test input, negatively correlated (out‐of‐phase) with tetanization of a separate, converging input, produces an NMDA‐independent, associative long‐term depression (LTD) of the test input synapses, in hippocampal field CA1 (Stanton and Sejnowski, 1989; Stanton et al., 1991). Associative LTD has also been observed in the dentate gyrus, in vivo, but only following “priming” of the test path with 5 Hz stimulation prior to associative conditioning (Christie and Abraham, 1992b). We have used these stimulus protocols, in vitro, in order to compare the induction of non‐associative and associative LTD in field CA1 of the adult rat hippocampus. Stimulation in normal solution evoked a small non‐associative LTD, but no associative LTD. Addition of picrotoxin to the medium facilitated the induction of NMDA‐dependent non‐associative LTD, but not associative LTD. Previously potentiated pathways were not different from naïve pathways in expression of LTD of either kind. Finally, ‘priming’ stimulation (5 Hz) of the test pathway produced a weak, selective enhancement of associative LTD that was, however, not significantly greater than non‐associative LTD. These results indicate that, for our experimental conditions, negatively correlated co‐activity during afferent tetanization does not induce a substantial associative LTD in area CA1. © 1993 Wiley‐Liss, Inc.
Quantitation and three‐dimensional reconstruction of Ch4 nucleus in the human basal forebrain
Authors: Halliday Glenda M. , Cullen Karen , Cairns Murray J. 
Published: December 2004

AbstractThe basal nucleus of Meynert, incorporating the Ch4 group of cholinergic neurons, was examined in six patients with no signs of neurological abnormalities. The ages of the patients ranged from 20 to 80 years. Despite a number of descriptions of these neurons, few age‐related studies have been dedicated to the analysis of the entire anteroposterior extent of the nucleus. Staining with cresyl violet and acetylcholinesterase histochemistry, alone or in combination, was used to identify the cytoarchitectural organization of the Ch4. Computer‐assisted morphometry was used for three‐dimensional visualization and quantitation. The three‐dimensional computer reconstructions revealed a continuous ribbon of neurons with a highly variable density. Four distinct subregions could be clearly identified in all cases by their cytoarchitecture and cellular morphology, although these subgroups were different to those previously described. There were no quantitative differences between the hemispheres in volume, density or cell number of the Ch4, although equivalent levels varied in area and density. The measures were similar in all cases with the exception of the case aged 80 years old. The data demonstrate individual variability in three dimensions and confirm previous studies that found only a mild decline of the Ch4 in old age. © 1993 Wiley‐Liss, Inc.
Muscarinic potentiation of excitatory amino acid‐evoked dopamine release in mesencephalic cells: Specificity for the NMDA response and role of intracellular messengers
Authors: Allaoua Horia , Chaudieu Isabelle , Alonso Richard , Quirion Rémi , Boksa Patricia 
Published: December 2004

AbstractOf the five cloned muscarinic receptor subtypes, dopamine (DA) neurons in the substantia nigra and ventral tegmental areas have been shown to be selectively enriched with the mRNA: for the m5 subtype, suggesting that muscarinic modulation of DA neurons may have a distinct pharmacology. In the present study we have used dissociated cell cultures of fetal rat ventral mesencephalon to characterize muscarinic modulation of DA neurons. [3H]DA release stimulated by activation of N‐methyl‐Daspartate (NMDA) receptors was potentiated by carbachol, a mixed muscarinic‐nicotinic agonist, and by oxotremorine‐M, a muscarinic agonist. Neither carbachol nor oxotremorine‐M had an effect on [3H]DA release evoked by the non‐NMDA agonists, kainate or quisqualate. A nicotinic agonist, DMPP, had no effect on NMDA‐stimulated release. Potentiation of NMDA‐stimulated [3H]DA release by oxotremorine‐M was inhibited by the broad spectrum muscarinic antagonist, QNB, and by low concentrations of a putative Ml antagonist, pirenzepine, while much higher concentrations of a purported M2 antagonist, AF‐DX 384, were required to reverse the oxotremorine‐M effect. The muscarinic antagonist, 4‐DAMP, was active in a concentration range between that required for pirenzepine and AF‐DX 384. Further experiments examined intracellular messenger mechanisms coupled to the muscarinic receptors modulating NMDA‐stimulated [3H]DA release. In contrast to oxotremorine‐M, two muscarinic agents with only weak partial agonism with respect to phosphoinositide turnover, pilocarpine and arecoline, had no effect on NMDA‐stimulated [3H]DA release. Potentiation of NMDA‐stimulated [3H]DA release by oxotremorine‐M was inhibited by staurosporinc, an inhibitor of protein kinase C, but was unaffected by H8, an inhibitor of cAMP‐ and cGMP‐dependent protein kinases. Pretreatment of cultures with pertussis toxin did not alter oxotremorine‐M potentiation of the NMDA response. Our results indicate that the muscarinic receptors responsible for potentiation of NMDA‐stimulated [3H]DA release in mesencephalic cultures are linked to phosphoinositide hydrolysis and protein kinase C activation via pertussis toxin insensitive G proteins. The data are also consistent with the identification of these receptors as the m5 subtype of cloned receptor, on the basis of the relative potency of muscarinic agonists and antagonists in this system, although involvement of ml receptors cannot be excluded solely on this basis. Taken together with previous reports showing selective localization of m5 receptor mRNA in regions containing DA cell bodies, these studies suggest that use of dissociated cell cultures may thus be an appropriate model for studying direct modulation of dopaminergic neurons by cholinergic agents interacting with putative m5 receptors. © 1993 Wiley‐Liss, Inc.