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1. |
SPECT imaging of dopamine and serotonin transporters with [123I]β‐CIT: Pharmacological characterization of brain uptake in nonhuman primates |
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Synapse,
Volume 13,
Issue 4,
1993,
Page 295-309
Marc Laruelle,
Ronald M. Baldwin,
Robert T. Malison,
Yolanda Zea‐Ponce,
Sami S. Zoghbi,
Mohammed S. Al‐Tikeriti,
Elzbieta H. Sybirska,
Ralph C. Zimmermann,
Gary Wisniewski,
John L. Neumeyer,
Richard A. Milius,
Shaoyin Wang,
Eileen O. Smith,
Robert H. Roth,
Dennis S. Charney,
Paul B. Hoffer,
Robert B. Innis,
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摘要:
AbstractSingle photon emission computed tomography (SPECT) studies of regional kinetic uptake and pharmacological specificity of [123I] methyl 3β‐ (4‐iodophenyl) tropane‐2β‐carboxylate ([123I]β‐CIT) were performed in nonhuman primates (n = 41). In control experiments, activity was concentrated in striatum and in hypothalamic/midbrain regions. Striatal uptake increased for 140–180 min and displayed stable levels thereafter. Striatal to cerebellar activity rations were 7.3 ± 0.9 (mean ± SEM) at 300 min. About 75% of striatal uptake was displaceable by injection of nonradioactive β‐CIT. Hypothalamic/midbrain activity reached maximal levels at approximately 45 min. A slow washout phase followed this peak activity. Activities in frontal, occipital, and cerebellar regions were characterized by an early peak (20–30 min), followed by rapid washout. Displacement studies demonstrated that striatal uptake was associated with dopamine (DA) transporters, as it was displaced by GBR 12909, a selective DA uptake inhibitor, but not by citalopram, a selective serotonin (5‐HT) uptake inhibitor. The inverse was true in the hypothalamic/midbrain area, suggesting that the uptake in this area was associated primarily with 5‐HT transporters. Maprotiline, a selective norepinephrine uptake inhibitor, did not affect [123I]β‐CIT uptake. In vivo site occupancy ED50values of cocaine, 2β‐carbomethoxy‐3β‐(4‐fluorophenyl) tropane (CFT), and β‐CIT were measured in the striatum with a stepwise displacement paradigm. In vivo ED50values correlated strongly with in vitro IC50values for binding to DA transporters. Infusion of high dose of L‐DOPA (250 μMol/kg) failed to displace striatal [123I]β‐CIT binding, suggesting that the binding would not be affected byL‐DOPA administration in Parkinsonian patients. However, studies performed with injection of d‐amphetamine indirectly suggested that high synaptic levels of DA may compete with [123I]β‐CIT binding, These studies suggest that [123I]β‐CIT will be a useful SPECT tracer of DA and 5‐HT
ISSN:0887-4476
DOI:10.1002/syn.890130402
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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2. |
Locomotor activity following intra‐accumbens microinjections of dopamine D1agonist SK&F 38393 in rats |
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Synapse,
Volume 13,
Issue 4,
1993,
Page 310-314
Merle E. Meyer,
Carol van Hartesveldt,
Thomas J. Potter,
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摘要:
AbstractThe present study examined the effects of the dopamine D1receptor subtypes agonist SK&F 38393 on locomotor activities after bilateral microinjection (0.00, 0.01, 0.1, 10.0 μg) into the nucleus accumbens (Acb). The dose of 0.1 μg elicited the highest response rate across measures of locomotion, rearing and stereotypy behavior. On the other hand, the largest dose of 10.0 μg was associated with significant increase in center time behaviors. The data were supportive of the hypothesis that dose‐related locomotor activities elicited by microinjections of SK&F 38393 into the Acb are independently mediated by D1receptors. © 1993 Wiley‐Li
ISSN:0887-4476
DOI:10.1002/syn.890130403
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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3. |
Glutamate effects on calcium homeostasis in cerebellar granule cells in primary cultures grown under depolarizing and nondepolarizing conditions |
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Synapse,
Volume 13,
Issue 4,
1993,
Page 315-321
Zhong Zhao,
Liang Peng,
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摘要:
AbstractCerebellar granule cell culture are normally grown under partly depolarizing conditions (in a medium with ∼25 mMK+), but these cultures can also be grown at a normal potassium concentration (5.4 mM k+), although some of their characteristics are altered. In this study, intracellular free calcium concentration and45Ca uptake were measured in cerebellar granule cell cultures grown at either 25 or 5.4 mM extracellular potassium in the presence of glutamate, and/or some of its subtype‐specific agonists and antagonists. Granule cells in cultures grown at 25mM K+responded to glutamate, but not to quisqualate, with an increase in free cytosolic calcium concentration and in45Ca uptake. This increase in free cytosolic calcium concentration was dependent on extracellular calcium and it was antagonized by AP5 and Ketamine, NMDA receptor antagonists. In contrast, granule cells in cultures grown at 5.4 mM K+responded to both glutamate and quisqualate, and these responses were independent of extracellular calcium and not sensitive to AP5 and ketamine. In agreement with this,45Ca uptake was not affected by glutamate. Neither of the two culture types responded to kainate with an increase in calcium concentration or uptake. These observations indicate that calcium uptake in granule cells in cultures grown at 25mM K+reflect NMDA activation of calcium influx, whereas the cells in cultures grown at 5 mM K+increase cytosolic calcium concentration on account of intracellular release of bound calcium, caused by activation of the metabotropic receptor. The two types of cultures may constitute valuable experimental tools for investigation of physiological and pathological effects of calcium releas from intracellular stores induced by glutamate via the metabotropic receptors and of calcium uptake induced by NMDA. © 1993 Wiley‐Lis
ISSN:0887-4476
DOI:10.1002/syn.890130404
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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4. |
Electrophysiological characterization of rat striatal neurons in vitro following a unilateral lesion of dopamine cells |
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Synapse,
Volume 13,
Issue 4,
1993,
Page 322-332
M. J. Twery,
L. A. Thompson,
J. R. Walters,
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摘要:
AbstractThe effects of a unilateral 6 to 19‐week lesion of dopamine cells on the excitability of rat striatal neurons were investigated in vitro using the intracellularly recorded membrane properties of neurons obtained ipsilateral and contralateral to 6‐hydroxydopamine (6‐OHDA) injection sites. Neurons ipsilateral to the lesion site and in striatal tissue depleted of dopamine exhibited resting membrane potentials and membrane resistances similar to those recorded in contralateral striatal neurons. Denervation appeared to have no appreciable effect on the proportion of neurons exhibiting various patterns of neuronal spiking (repetitive, bursting, or single spike) evoked by depolarizing current pulses. Current‐voltage determinations revealed nominal rectification in the majority of neurons and marked nonlinearty consistent with inward rectification at potentials hyperpolarized and depolarized to rest in a large proportion of the remaining neurons. Neurons ipsilateral to 6‐OHDA lesion sites exhibited these relationships in the same proportion as contralateral control cells. However, ipsilateral neurons with nominal rectification exhibited an average rate constant for the early onset of small hyperpolarizing membrane transients which was significantly smaller than that of controls. This finding suggests that intrinsic membrane parameters regulating the excitability of certain striatal neurons may be under the influence of dopamine or other factors closely associated with nigrostriatal nerve terminals. Published 1993 Wiley
ISSN:0887-4476
DOI:10.1002/syn.890130405
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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5. |
Serotonin‐induced increase in cAMP in ganglia isolated from the myenteric plexus of the guinea pig small intestine: Mediation by a novel 5‐HT receptor |
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Synapse,
Volume 13,
Issue 4,
1993,
Page 333-349
Elena Fiorica‐Howells,
Paul R. Wade,
Michael D. Gershon,
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摘要:
AbstractSerotonin (5‐HT) is a mediator (through 5‐HT1Preceptors) of slow EPSPs in myenteric ganglia of the small intestine. The effect of 5‐HT can be mimicked by elevating cAMP; therefore, we tested the hypothesis that the slow EPSP‐like response to 5‐HT is cAMP‐mediated. Guinea pig gut was enzymatically dissociated; myenteric ganglia remained intact and were collected by filtration. Neurons in the isolated ganglia retained their ability to manifest the slow EPSP‐like response to 5‐HT. Exposure to 5‐HT raised the ganglionic level of cAMP (ED500.3 μM). This effect was not antagonized by the 5‐HT1Pantagonist, N‐acetyl‐5‐hydroxytryptophyl‐5‐hydroxytryptophan amide (100.0 μM), or mimicked by the 5‐HT1Pagonist, 5‐hydroxyindalpine (10.0 μM). Increases in cAMP were also evoked by the 5‐HT1agonist, 5‐carboxyamidotryptamine (10.0 μM), the 5‐HT2agonist, (±)‐1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI; 1.0–10.0 μM), and by the 5‐HT4agonists, renzapride (1.0–10.0 μM) and 5‐methoxytryptamine (1.0–10.0 μM); however, neither the 5‐HT1/5‐HT2antagonists, spiperone, methysergide, and methiothepin, nor the 5‐HT4antagonist, tropisetron (ICS 205–930; 10.0 μM), were able to inhibit the rise in cAMP evoked by these compounds or by 5‐HT (0.1–10.0 μM). The 5‐HT‐evoked elevation of cAMP was antagonized by ketanserin (10.0 μM), which also blocked the effects of 5‐methoxytryptamine and DOI, but not those of renzapride. The effective concentration of DOI, however, was higher than that needed for activation of 5‐HT2receptors, and Northern analysis using a cDNA probe encoding the rat 5‐HT2receptor failed to reveal the presence of 5‐HT2mRNA in myenteric ganglia, although it hybridizes with mRNA of the right size in the guinea pig brain. Compounds that failed to change levels of cAMP or to antagonize the action of 5‐HT included 8‐hydroxy‐di‐n‐propylamino tetralin, R58639, R88226, and sumatriptan. It is concluded that the receptor responsible for the 5‐HT‐induced rise in cAMP in ganglia isolated from the guinea pig myenteric plexus is not a known subtype of 5‐HT receptor. Since the pharmacology of this novel receptor is different from that of
ISSN:0887-4476
DOI:10.1002/syn.890130406
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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6. |
Striatal binding of the PET ligand11C‐raclopride is altered by drugs that modify synaptic dopamine levels |
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Synapse,
Volume 13,
Issue 4,
1993,
Page 350-356
Stephen L. Dewey,
Gwenn S. Smith,
Jean Logan,
Jonathan D. Brodie,
Joanna S. Fowler,
Alfred P. Wolf,
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摘要:
AbstractBilatera decreases in striatal11C‐raclopride binding were observed in adult female baboons with high resolution PET following administration of drugs that act centrally on dopaminergic neurons. At baseline and following administration of d‐amphetamine (a dopamine‐releasing drug), GBR‐12909 (a potent dopamine reuptake inhibitor), or tetrabenazine (a biogenic amine depleting drug) PET scans of11C‐raclopride binding were obtained in a CTI 931 positron tomograph. In all studies, the ratio of the distribution volumes for the striatum to the cerebellum for11C‐raclopride binding decreased significantly by an average of 16.2% for d‐amphetamine, 22.1% for GBR‐12909, and 28.3% for tetrabenazine while there were no significant changes observed in the cerebellum or in the rate of systemic metabolism of the radiotracer. These decreases exceed the test/retest variability of striatal11C‐raclopride binding measured in the same animals under identical experimental conditions (Dewey et al., 1992b). Together these studies demonstrate that PET measurements of striatal11C‐raclopride binding can be used to indirectly and non‐invasively monitor changes in synaptic dopamine concentrations that result from a variety of neurophysiologic mechanisms.
ISSN:0887-4476
DOI:10.1002/syn.890130407
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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7. |
Molecular alterations in the neostriatum of human cocaine addicts |
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Synapse,
Volume 13,
Issue 4,
1993,
Page 357-369
Yasmin L. Hurd,
Miles Herkenham,
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摘要:
AbstractMolecular changes in the neostriatum of human subjects who died with a history of cocaine abuse were revealed in discrete cell populations by means of the techniques of in situ hybridization histochemistry and in vitro receptor binding and autoradiography. Cocaine subjects had a history of repeated cocaine use and had cocaine and/or cocaine metabolites on board at the time of death. These subjects were compared to control subjects that had both a negative history and toxicology of cocaine use. Selective alterations in mRNA levels of striatal neuropeptides were detected in cocaine subjects compared to control subjects, especially for the opioid peptides. Marked reductions in the levels of enkephalin mRNA and μ opiate receptor binding were found in the caudate and putamen, concomitant with elevations in levels of dynorphin mRNA and κ opiate receptor binding in the putamen and caudate, respectively. Dopamine uptake site binding was reduced in the caudate and putamen of cocaine subjects. The greater magnitude of changes in the dorsolateral striatum (caudate and putamen) as opposed to the ventromedial striatum (nucleus accumbens) suggests that cocaine abuse preferentially alters the biosynthetic activity of striatal systems associated with sensorimotor functioning. Additionally, an imbalance in the activity of the two major striatal output pathways in cocaine users is implicated because peptide mRNA levels were reduced in enkephalinergic striatopallidal neurons and increased in dynorphinergic striatonigral neurons. Another imbalance, that of reductions of transmitter mRNA and receptor expression associated with euphoria (enkephalin and μ opiate receptors), together with elevations in mRNAs of transmitter systems associated with dysphoria (dynorphin and κ opiate receptors), suggests a model of dysphoria and craving in the human cocaine addict brain. © 1993 Wiley‐Lis
ISSN:0887-4476
DOI:10.1002/syn.890130408
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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8. |
Further studies concerning the role of nitric oxide in LTP induction and maintenance |
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Synapse,
Volume 13,
Issue 4,
1993,
Page 370-375
Wael Y. Musleh,
Kavian Shahi,
Michel Baudry,
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摘要:
AbstractNitric oxide (NO) has recently been proposed to act as a retrograde messenger to produce long‐term potentiation (LTP) in hippocampal area CA1. This notion is based largely on the absence of LTP when hippocampal slices are incubated in the presence of inhibitors of NO synthase (NOS) or of NO scavengers. In the present study, we tested the effects of such compounds on both the induction and maintenance of LTP in field CA1 of hippocampal slices. Incubation of slices in the presence of N‐methyl‐L‐arginine (MLA) orL‐nitroarginine (LNA), two inhibitors of NOS, or in the presence of hemoglobin (Hb), a NO scavenger, produced a large reduction in the magnitude of LTP induced by a theta burst stimulation (TBS) paradigm. These compounds had no effect on the degree of paired‐pulse facilitation but produced a significant reduction of the facilitation of postsynaptic responses occuring during TBS. On the other hand, MLA did not prevent the potentiation induced by application of tetraethylammonium (TEA). These results suggest that the inhibition of LTP produced by these agents could be due to an effect on a physiological mechanism that triggers LTP and not necessarily on an event that follows the triggering step. © 1993 Wil
ISSN:0887-4476
DOI:10.1002/syn.890130409
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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9. |
Extracellular glutamate levels increase with age in the lateral striatum: Potential involvement of presynaptic D‐2 receptors |
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Synapse,
Volume 13,
Issue 4,
1993,
Page 376-382
Bruce A. Donzanti,
Juliana F. Hite,
Bryan K. Yamamoto,
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摘要:
AbstractIn the lateral striatum of aged rats, dopamine D‐2 receptor density is reduced and glutamate tissue content is elevated. D‐2 receptor agonists have been shown to inhibit stimulated glutamate release. In the present study, microdialysis was used to investigate a potential role for D‐2 receptors in the modulation of striatal glutamate efflux from 4‐, 12‐, 18‐, and 24–26‐month‐old Fischer 344 rats. Extracellular basal glutamate concentrations significantly increased as a function of age in the lateral, but not medial, striatum. Neither the D‐2 agonist, LY 163502, nor the D‐2 antagonist, sulpiride, influenced basal glutamate efflux, suggesting that the dopaminergic system is not involved in the observed age‐related increase in extracellular basal glutamate levels. In contrast to basal efflux, potassium‐evoked glutamate release was not altered with age. However, LY 163502 significantly inhibited stimulated glutamate release in 4‐month‐old rats. This inhibitory action was not observed at any other age. Sulpiride alone did not alter stimulated glutamate release, but it did block the inhibitory effect of LY 163502 in the 4‐month‐old rats. These results provide in vivo evidence for an age‐related functional loss in the modulation of striatal glutamate release by dopamine D‐2 receptors in addition to increased basal glutamate efflux, which is not related to D‐2 receptor modulation. Such mechanisms could be important in the pathophysiology of striatal cell death during aging and age‐related neurodege
ISSN:0887-4476
DOI:10.1002/syn.890130410
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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10. |
Announcement |
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Synapse,
Volume 13,
Issue 4,
1993,
Page 388-388
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ISSN:0887-4476
DOI:10.1002/syn.890130411
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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