摘要:

AbstractWe have compared rapid freezing followed by freeze‐substitution fixation with conventional aldehyde fixation as preparative methods for the electron microscopic study of organotypic cultures of neonatal rat hippocampus. Rapid freezing by contact with a copper block chilled by liquid helium was accomplished without mechanical distortion of superficial structures, and preserved structure to a depth of at least 20 μM without visible ice crystals. Freeze‐substitution fixation in acetone/osmium tetroxide, followed by en bloc staining with tannic acid and uranyl acetate, provided satisfactory staining of cytoplasm and organelles. While both preparative techniques yielded generally satisfactory results, rapid freezing provided much better preservation of astrocytic lysosomal inclusions, and afforded new views of intermediate filament substructure. Rapid freezing and freeze‐substitution fixation seemed especially well suited to the preservation of short filamentous proteins, such as those forming the membrane cytoskeleton of dendritic spines or those associated with synaptic vesicles. The combination of rapid freezing methods and organotypic culture provides an opportunity to examine cytoplasmic structure in tissue from deep regions of the brain which had previously been inaccessible to rapid freezing techniques. © 1993 Wiley‐

ISSN:0887-4476    

DOI:10.1002/syn.890130302

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

年代:1993

数据来源: WILEY

摘要:

AbstractSpecies differences in the distribution of β‐adrenergic receptors in the hippocampal and retrohippocampal regions of rats and guinea pigs were examined using in vitro autoradiographic techniques. β1‐receptors were found in the hippocampal area CA1 of both species, although guinea pigs had significantly lower receptor densities in comparison to rats. In guinea pigs, β2‐adrenergic receptors were predominant in hippocmpal area CA1. Hippocampal area CA3 had very low levels of β1‐ and β2‐receptors in both species. The retrohippocampal area was also found to have a distinct topographic distribution of β‐receptors. In rats, the subiculum and parasubiculum (layers II‐III) were heavily labeled for β1‐receptors; in contrast, guinea pigs had few receptors in these regions. β2‐receptors were particularly prominent in the parasubicular region in rats. The entorhinal cortex laminae was found to contain β‐receptors in both rats and guinea pigs. Immunohistochemical techniques were used to compare the pattern of catecholaminergic innervation with the receptor distribution within each hippocampal subregion. Despite the general lack of β‐receptors in area CA3, abundant catecholamine immunoreactive fibers were observed in CA3 of rat and guinea pig hippocampus. Significant species differences were found in the distribution of hippocampal β‐adrenergic receptor subtypes, and moreover, in both species the distribution of hippocampal β‐adrenergic receptors did not coincide with the pattern of hippocampal adrenergi

ISSN:0887-4476    

DOI:10.1002/syn.890130303

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

年代:1993

数据来源: WILEY

摘要:

AbstractThere is an acute interest in studying the functional characteristics of dopamine systems in the cortex of primates. In particular, the prefrontal cortical dopamine projections have received a great deal of attention. This system is essential for proper functioning of the prefrontal cortex, and dysfunction within the system may be involved in some psychiatric and neurological illnesses. In vivo assessments of cortical dopamine in the primate have been scarce. This has been due, in part, to technical difficulties associated with these studies and with quantifying the relatively low levels of dopamine found in cortical regions. In the present study, intracerebral microdialysis was utilized to assess the extracellular concentration of dopamine in cortical and subcortical areas of the pentobarbital‐anesthetized rhesus monkey. Basal extracellular dopamine levels were consistently detected in the medial prefrontal cortex, premotor cortex, and caudate‐putamen. The basal extracellular concentration of dopamine in the dorsolateral prefrontal cortex was reliably detected in 1 of 4 animals. Intravenous administration of amphetamine (1 mg/kg) enhanced extracellular dopamine levels in the caudate‐putamen area by more than 20‐fold. In cortical areas, amphetamine's effect was less profound: An increase of 400–500 percent over basal extracellular dopamine levels was observed in each region. These studies demonstrate the feasibility of microdialysis for detecting extracellular fluxes of dopamine in the cortex of nonhuman primates. They further provide direct evidence that the dopamine released within the prefrontal cortex and the premotor cortex of nonhuman primates responds to pharmacological manipulation. © 1993 Wiley

ISSN:0887-4476    

DOI:10.1002/syn.890130304

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

年代:1993

数据来源: WILEY

摘要:

AbstractAcute and repeated administration of antipsychotic drugs produce distinctive profiles of electrophysiological effects on the population activity of midbrain dopaminergic (DA) neurons which correlate with their clinical effects.Sigmareceptors have been hypothesized to be involved in psychosis and in the efficacy of antipsychotic drugs, but little is known about the effects of repeated treatment withsigmaligands on the activity of midbrain DA neuronal populations. In the present study, the cells‐pertrack cell‐sampling method was used to evaluate the effects of 3sigmaligands on the numbers of spontaneously active A9 and A10 DA neurons in chloral hydrate‐anesthetized rats. One‐hour pretreatment with either (+)‐pentazocine (10 mg/kg, i.p.), DTG (2 mg/kg, i.p.), or JO 1784 (1 or 10 mg/kg, s.c.) did not alter the number of spontaneously active DA neurons encountered per electrode track. Repeated treatment (21 daily injections) with (+)‐pentazocine (1 or 10 mg/kg) or DTG (0.2 or 2 mg/kg) increased the number of A10 DA cells per track; JO 1784 (10 mg/kg but not 1 mg/kg) moderately decreased the number of active A9 DA cells and increased the firing rate of A10 DA neurons. The effect of JO 1784 on A9 DA neurons was not due to depolarization inactivation. The effects of all 3sigmaligands differ from those of antipsychotic drugs, all of which inactivate A10 DA neurons after repeated treatment. Clinical studies are necessary to determine if selectivesigmaligands will provide a novel alternative to DA antagonists in the treatment of psychosis. © 1993 Wil

ISSN:0887-4476    

DOI:10.1002/syn.890130305

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe distribution of β‐opioid binding sites was studied by quantitative autoradiography in rat brain and spinal cord using the highly selective ligand [125I][D. Ala2]deltorphin‐I. The binding properties of [125I][D. Ala2]deltorphin‐I were investigated by microdensitometry of autoradiographic films with the aid of a computerassisted image‐analysis system. [125I][D. Ala2]deltorphin‐I appeared to interact with a single class of sites in all brain areas (KD= 0.9 nM). In 23 regions tested, whatever the δ site concentration, DTLET, a δ agonist, appears to be 2 orders of magnitude more effective than DAGO, a μ agonist, in inhibiting specific [125I][D. Ala2]deltorphin‐I binding. The distribution of [125I][D. Ala2]deltorphin‐I sites is globally consistent with that of other δ ligands and does not support the existence of a δ‐receptor subtype recognized by [D. Ala2]deltorphin‐I. [125I][D. Ala2]deltorphin‐I binding sites were highly confined, exhibiting selective localization in the neocortex and a diffuse pattern in the striatum, accumbens nucleus, claustrum, layer of bulb, amygdaloid nucleus, pontine nuclei, and inferior colliculus. In several areas a rostro‐caudal gradient of site concentration was indicated. [D. Ala2]deltorphin‐I binding sites were also present in the substantia gelatinosa at all levels of the spinal cord and, unexpectedly, in deeper laminae and the ventral horn. These results demonstrate the ability of [125I][D. Ala2]deltorphin‐I to characterize low concentrations of binding sites and to reveal new localizations of δ r

ISSN:0887-4476    

DOI:10.1002/syn.890130306

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

年代:1993

数据来源: WILEY

摘要:

AbstractChronic in utero methamphetamine treatment, throughout gestation in rats, resulted in alterations in both behavior and brain monoamine function in the adult offspring. The higher dose of methamphetamine (10 mg/kg/b.i.d.) caused a significant decrease in square crossing and rearing in an open field, as well as a region increase of serotonin and dopamine uptake sites. In contrast, the lower dose of in utero methamphetamine (2 mg/kg/b.i.d.) resulted in a significant decrease in regional densities of serotonin and dopamine uptake sites, and only decreased rearing behavior. Across treatment groups, there were significant correlations between open‐field square crossing activity and the number of uptake sites in specific brain areas. Other measured behaviors, such as the neonate righting reflex and the adult Morris water maze performance, were unaffected by either in utero drug regimen. These results are discussed in terms of the known neurotoxicity of amphetamines and the ability of the immature nervous system to compensate for fetal exposure to methamphetamine. © 1993 Wiley‐Liss,

ISSN:0887-4476    

DOI:10.1002/syn.890130307

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe influence of the mesencephalic dopaminergic projections on the neurons within the basal forebrain and prefrontal cortex is not well understood although it has been intensely investigated. The purpose of this study was to evaluate the expression of Fos‐like and FRA‐like (Fos Related Antigens) immunoreactivity (IR) as a qualitative and quantitative marker of neuronal activity within the mesolimbic and mesostriatal dopamine terminal fields. Following the administration of apomorphine (5.0 mg/kg S.C.), a rapid increase in FRA‐IR, accompanied by Fos‐IR, was observed within the striatum in a patchy distribution. Apomorphine also induced the expression of FRA‐IR within the nucleus accumbens, cortex, septum, and the islands of Calleja complex. This broad pattern of activation contrasts with the limited expression of Fos‐IR and FRA‐IR within the dorsolateral striatum, dorsomedial shell of the nucleus accumbens, and cingulate cortex following haloperidol administration (2.0 mg/kg, S.C.). Finally, it was observed that nuclei expressed Fos‐IR rapidly and transiently within the striatum following haloperidol, whereas the number of FRA‐IR nuclei remained elevated but changed in distribution and intensity over time. In conclusion, different regions within the dopamine terminal fields express varying concentrations of Fos‐IR and FRA‐IR after stimulation or blockade of dopamine receptors. These data indicate that Fos, as well as selective FRAs, can be used to delineate populations of neurons with altered metabolic activity resulting from the administration of dopaminergic agents. Furthermore, the data support the concept of segregated mesostriatal and mesolimbic projections, in particular the divison of the nucleus accumbens into the shell and core compartments.

ISSN:0887-4476    

DOI:10.1002/syn.890130308

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

年代:1993

数据来源: WILEY

摘要:

AbstractIn rats bearing unilateral 6‐hydroxydopamine (6‐OHDA) lesions of the dopaminergic nigro‐striatal neurons, a single administration of a D‐2 agonist (LY 17155) potentiates the contralateral turning induced by a D‐1 agonist (SKF 38393). To identify the neural substrate of this form of sensitization (priming), we studied the local cerebral glucose utilization (lCMRglc) in 6‐OHDA lesioned animals treated, 3 days apart, as follows: (1) saline‐saline, (2) LY 171555‐saline, (3) saline‐SKF 38393 and (4) LY 171555‐SKF 38393. The unilateral 6‐OHDA lesion per se (Sal‐Sal) produced increases in lCMRglcin the globus pallidus (GP) and in the lateral habenula (LH) of the lesioned hemisphere. lCMRglcin LY‐Sal group were similar to those measured in the Sal‐Sal group. Administration of SKF 38393 to drug‐naïve rats (Sal‐SKF) abolished the lesion‐induced metabolic asymmetry in the LH but did not have any effect on the GP; furthermore, it increased lCMRglcin the substantia nigra pars reticulata (SNr) of the lesioned side. After priming with LY 171555, administration of SKF 38393 (LY‐SKF) produced marked metabolic asymmetries by increasing lCMRglcin the SNr and entopeduncular nucleus (EP), and decreasing it in the LH of the lesioned side. These changes were also significant when compared to the corresponding values of the other experimental groups. Again, in LY‐SKF group no modification of the lesion‐induced metabolic asymmetry in the GP was found. These results indicate that priming exerts a facilitatory influence on the ability of D‐1 receptors to stimulate the striato‐nigral and striato‐entopeduncular pathway, suggesting that changes in the effectiveness of dopamine in activating its postsynaptic target elements might contribute to the mechanism of sensitization to drugs stimulating dop

ISSN:0887-4476    

DOI:10.1002/syn.890130309

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

年代:1993

数据来源: WILEY

摘要:

AbstractIn vitro extracellular single‐unit recordings from rat midbrain slices were used to assess the effects of excitatory amino acid agonists on the activity of A10 dopamine neurons. N‐methyl‐D‐aspartic acid (NMDA), kainic acid (KA), and β‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) elicited dose‐dependent increases in firing rates. The relative potencies for the 3 compounds was AMPA>KA>NMDA. None of the excitations was accompained by burst firing, but frequently periods of nonrecordable activity occurred following pronounced stimulation. Concurrent application of the excitatory amino acid antagonist CGS 19755 (cis‐4‐phosphonomethyl‐2‐piperidine carboxylate) selectively blocked the excitations elicited by NMDA but not by KA or AMPA. Likewise the selective non‐NMDA antagonist NBQX [2,3‐dihydroxy‐6‐nitro‐7‐sulfamoyl‐benzo(F)quinoxaline] blocked only the excitatory effects of AMPA and KA but not those elicited by NMDA. NBQX appeared to be less optent at antagonizing KA than AMPA. These results suggest that mesolimbic‐mesocortical dopamine neurons possess both NMDA and non‐NMDA receptors, and possibly distinct AMP

ISSN:0887-4476    

DOI:10.1002/syn.890130310

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

年代:1993

数据来源: WILEY

摘要:

AbstractUntil recently, research on the neurochemical basis of affective disorders (AD) and schizophrenia (SCZ) focused on detecting postulated disturbances in presynaptic neurotransmitter release and metabolism, or postsynaptic receptor function. New insights into the molecular mechanisms involved in the propagation of neurotransmitter signals across biological membranes and in the regulation of neuronal responses have allowed the development of novel hypotheses, which may explain the altered postsynaptic neuroreceptor responsivity thought to be integral to the pathophysiology of these disorders. In this review we evaluate evidence from both basic science and clinical research implicating disturbances in postreceptor signal transduction in the pathophysiology and pharmacotherapy of AD and SCZ. Specific findings regarding potential postreceptor sites of pathophysiology are highlighted in each of these disorders, together with the growing body of data on the possible postreceptor loci of psychotropic drug action, especially lithium and antidepressants. © 1993 Wiley‐Liss, I

ISSN:0887-4476    

DOI:10.1002/syn.890130311

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

年代:1993

数据来源: WILEY