摘要:

AbstractThis study was designed to determine the effects of N‐methyl‐D‐aspartate (NMDA) receptor stimulation on the electrical activity of neocortex in freely behaving rats. Electroencephalogram (EEG) recording and intracerebral microdialysis were conducted simultaneously in the same site of the sensorimotor cortex, where the basal extracellular concentrations of aspartate and glutamate were 2.1 ± 0.7 m̈M and 11.5 ± 2.4 m̈M, respectively. Microdialysis with NMDA solutions (ranging from 10.0 m̈M to 10.0 mM) reduced the amplitude of the EEG activity and decreased the power of all frequency bands, with a virtual elimination of the high frequency waves, in a dose‐dependent manner. These EEG changes were reversed after washing out the drug from the microdialysis fluid, and could be effectively antagonized with the competitive NMDA receptor antagonistDL‐2‐amino‐5‐phosphonovalerate. Remarkably, the NMDA actions were not associated with epileptiform behavioral or electrographic events. Control studies demonstrated that in the same experimental conditions, cholinergic receptor agonist carbachol caused seizures, and microdialysis with NMDA in the hippocampus readily induced epileptiform spikes. Our study shows that NMDA receptor stimulation in the rat sensorimotor cortex, although excitatory at synaptic level, can depress the local EEG activity. This may indicate that the NMDA receptor‐mediated signals are processed by the neocortical network in a different way than by many other brain circuitries including hippocampus.

ISSN:0887-4476    

DOI:10.1002/syn.890120202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractCFT [WIN 35, 428, 2β‐carbomethoxy‐3β‐(4‐fluorophenyl)tropane] and its 4‐iodinated analog RTI‐55 have been proposed as imaging probes for cocaine recognition sites and for dopamine transporters. The central and peripheral distribution of radiolabeled forms of these compounds was studied 30 minutes after intravenous administration in squirrel monkey (Saimiri sciureus). Quantitative ex vivo autoradiography of brain tissue sections from animals receiving [3H]CFT (2.5 nmol/kg) revealed radioligand distribution primarily in dopamine‐rich brain regions, and treatment with cocaine or mazindol substantially reduced [3H]CFT accumulation. The caudate nucleus, putamen, and nucleus accumbens/olfactory tubercle accumulated the highest levels of [3H]CFT, and within the caudate nucleus, medial‐to‐lateral and anterior‐to‐posterior gradients were observed. Low levels of [3H]CFT were found in the cortex, thalamus, hypothalamus, and background levels in white matter and in the cerebellum (striatal: cerebellar ratio>3). The in vivo distribution of [3H]CFT closely paralleled its in vitro distribution (Synapse, 9:177–187). Although [125I]RTI‐55 (0.2 nmol/kg) also distributed to dopamine‐rich brain regions (striatal: cerebellar ratio of 3.6), high levels also were detected in cortex, thalamus, and in midbrain/brainstem structures. In the periphery, [125I]RTI‐55 accumulation, measured as percent of administered dose, was higher than [3H]CFT in liver and lung, greater than 90% comigrated with [3H]CFT or [125I]RTI‐55 standards. The results support the hypothesis that dopamine‐rich brain regions may be relevant to the effects of cocaine, and that both CFT and RTI‐55 may be su

ISSN:0887-4476    

DOI:10.1002/syn.890120203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractNeuronal activation increases levels of Fos protein, the product of the early immediate genec‐fos. Since most studies used stimuli that evoke sustained elevations in activity; the present study examined Fos‐like immunoreactivity (Fos‐LI) in the nucleus locus coeruleus (LC). Halothane‐anesthetized rats were given either footshock to elicit phasic activation of LC neurons or yohimbine (10 mg/kg, i. p.) to induce a tonic increase in firing. Both treatments markedly increased Fos‐LI in a subpopulation of LC neurons. These results demonstrate thatc‐fosinduction does not require high tonic levels of neuronal activity and that Fos‐LI may underestimate the proportion of LC neurons neurophysiologically activated by a given stimulus and suggest that factors beyond neuronal activity per se contributes toc‐fosexpression. © 1992

ISSN:0887-4476    

DOI:10.1002/syn.890120204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractSPECT imaging of benzodiazepine (BZ) receptor using the antagonist [123I]iomazenil in nonhuman primates was correlated with ex vivo autoradiography and in vitro receptor autoradiography of postmortem tissue sections taken at the time of maximal brain uptake of the radiotracer. Cryostat sections prepred from brain tissue blocks at the orientation of the SPECT imaging plane showed high activity in gray matter regions, with gray to white matter ratios of greater than 30:1. After at least one week decay of123I, these same tissue sections were used to localize and quantify the distribution of BZ receptors with the standard technique of in vitro receptor autoradiography using [125I]iomazenil. The ex vivo autoradiographic distribution of activity was highly correlated (r = 0.89) with the distribution of BZ receptors, although a few brain regions showed reproducible discrepancies between ex vivo and in vitro results. The ex vivo autoradiograms provided quantitative data from a realistic “biological phantom,” which may be used to assess the accuracy of image reconstruction and to investigate differences between the distribution of an intravenously (i. v.) administered tracer and that of its target in brain tissue. © 1992 Wiley‐Lis

ISSN:0887-4476    

DOI:10.1002/syn.890120205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractStudies on the mechanisms of tolerance and dependence have mostly focused on changes at the receptor level. These experiments, conducted with model systems ranging from clonal cell lines to whole animals, have identified a number of important adaptive mechanisms which occur at the receptor level. However, none of these adaptive mechanisms can completely account for the phenomena which serve to define the state of morphine tolerance and dependence, especially the observation that as an animal becomes more tolerant to morphine, less naloxone is required to trigger withdrawal. The data reviewed in this paper provide strong support for the hypothesis that the brain synthesizes and secretes neuropeptides which act as part of a homeostatic system to attenuate the effects of morphine and endogenous opioid peptides. According to this model, administration of morphine releases anti‐opioid peptides (AOP), which then attenuate the effects of morphine. As more morphine is given, more AOP are released, thereby producing tolerance to the effects of morphine. Cessation of morphine administration, or administration of naloxone, produces a relative excess of anti‐opioid, which is in part responsible for the withdrawal syndrome. Since endogenous and exogenous antagonists might together produce synergistic effects, less naloxone might be required to trigger withdrawal in the presence of higher levels of AOPs. Although the study of AOP is in its infancy, a deeper understanding of the central nervous system (CNS) anti‐opioid systems may lead to new treatments for chronic pain, substance abuse, and psychiatric disorders. © 1992 Wiley‐L

ISSN:0887-4476    

DOI:10.1002/syn.890120206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractWhile neurons containing immunoreactive luteinizing hormone‐releasing hormone (LHRH) are scattered primarily in the medial septal‐diagonal band of Broca‐medial preoptic area (mS‐dbB‐PO) complex, autoradiographic studies have demonstrated dense concentrations of LHRH receptors in the hippocampus. The route by which LHRH is transported to its hippocampal receptors is unknown. The present study was designed to test the hypothesis that LHRH‐containing neurons in the mS‐dbB‐PO complex project to hippocampal sites containing LHRH receptors, thereby serving as a source of innervation to these receptors.Large (0.10 m̈l) or small (0.02 m̈l) volumes of the retrograde tracer wheat germ agglutinin (WGA) were injected unilaterally into four separate hippocampal locations in six ovariectomized female rats. In an additional five females, a 0.15 m̈l volume of the retrograde tracer fluorogold (FG) was similarly injected. After a five day survival period, the animals were sacrificed. Vibratome sections of the brain were stained for both WGA and LHRH with a dual immunohistochemical technique. Since FG is a fluorescent chromagen, brains of animals injected with FG only required processing for LHRH immunofluorescence. As a positive control, some sections containing retrogradely labeled cells filled with either WGA or FG were processed for choline acetyltransferase (CHAT) immunoreactivity.The WGA and FG injections covered targeted hippocampal sites and neurons containing retrogradely transported WGA or FG were found in abundance in the mS‐dbB‐PO complex. In accord with previous reports, many CHAT‐positive and fewer LHRH‐positive neurons were found in this complex. Approximately 5–10% of the CHAT‐positive neurons also contained WGA or FG; however, no neurons were found to co‐localize LHRH and either of the retrograde tracers. The results indicate that LHRH neurons in the mS‐dbB‐PO complex do not project directly to hippocampal sites containing LH

ISSN:0887-4476    

DOI:10.1002/syn.890120207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe effects of chronic intermittent administration (7 months) of two neuroleptics, haloperidol (HAL) and raclopride (RAC), were compared using several different measures. Both drugs were administered weekly by subcutaneous injection at 7.0 mg/kg. Both neuroleptics consistently produced catalepsy throughout the treatment period, although HAL was generally more cataleptogenic than RAC. Assessment of dopamine (DA) release in the caudate putamen (CPu), through the use of in vivo microdialysis, showed that chronic HAL or RAC administration caused a prolonged decrease of DA release in response to a low dose of the DA D2 agonist quinpirole (0.03 mg/kg, sc). Injection of the muscarinic agonist pilocarpine (1.0 mg/kg, IP) did not have any significant within‐group effects, although both neuroleptic treatment groups showed decreased DA release when compared to controls. Ultrastructural analysis of the dorsolateral CPu showed that both HAL and RAC treatment resulted in a significant increase in the number of perforated synapses, which contain a discontinuous density along the postsynaptic membrane. These results demonstrate that two different DA D2 receptor antagonists produce a similar effect on DA function and ultrastructural changes within the CPu following chronic, intermittent treatment. © 1992 Wiley‐Liss,

ISSN:0887-4476    

DOI:10.1002/syn.890120208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractParafollicular (PF) cells of the thyroid gland are neural crest derivatives, which costore the neurotransmitter, 5‐hydroxytryptamine (5‐HT) with calcitonin. PF cells are located adjacent to follicular (F) cells within the basement membrane of thyroid follicles. It has been proposed that 5‐HT serves an intercellular signalling function in the thyroid and that F cells are its target. This proposal was tested by using cell lines derived from PF (medullary thyroid carcinoma [MTC]) and F (FRTL‐5) cells to study the mechanisms that mediate the secretion and action of 5‐HT. Secretion of 5‐HT by MTC cells was evoked by thyroid stimulating hormone, thyrotropin (TSH), elevated extracellular calcium (↑[Ca2+]e), or by agents that increase intracellular cAMP (↑[cAMP]i). When protein kinase C (PKC) was down‐regulated by prolonged treatment of MTC cells with phorbol 12‐myristate 13‐acetate (PMA), or PKC was inhibited by staurosporin, the TSH‐or PMA‐evoked secretion of 5‐HT was blocked; however, interference with PKC function did not affect 5‐HT secretion evoked by ↑ [Ca2+]eor ↑ [cAMP]i. In the putative targets, FRTL‐5 cells, 5‐HT increased the turnover of phosphoinositides (PI), cytosolic calcium (↑[Ca2+]i), ↑[cAMP]i, and biphasically modified the effect of TSH on cAMP. All of these 5‐HT effects were inhibited by 5‐HT2receptor antagonists (spiperone and ketanserin) and by pertussis toxin (PTx), suggesting that the actions of 5‐HT are mediated by 5‐HT2receptors, which are coupled to a G protein. This suggestion was supported by the following additional observations: FRTL‐5 membranes bound the 5‐HT2agonist, [125I]2,5‐dimethoxy‐4‐iodophenylisopropylamine ([125I]‐DOI), and anti‐idiotypic anti‐bodies, which recognize 5‐HT2receptors. [125I]‐DOI binding was inhibited by guanosine‐5′‐O‐(3‐thiotriphosphate) (GTP‐γ‐S) and the antibodies were displaced by spiperone. Data are consistent with

ISSN:0887-4476    

DOI:10.1002/syn.890120209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890120210

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890120201

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY