摘要:

AbstractThe effects of haloperidol and clozapine on tachykinin tissue lelvels, preprotachykinin‐A messenger RNA, spontaneous and potassium‐evoked tachykinin release, dopamine D2receptors, and [125]Bolton‐Hunter‐substance P binding sites in the striato‐nigral system were examined. Chronic administration (10 days) of the dopamine receptor antagonist haloperidol (2 mg/kg, i.p.) significantly decreased tissue levels of substance P like‐immunoreactivity and neurokinin A like‐immunoreactivity in the striatum and the substantia nigra. The corresponding preprotachykinin‐A mRNA was decreased ub tge struatyun, Haloperidol did not affect the potassium‐evoked tachyikinin release in the substantia nigra but significantly increased the spontaneous release. Haloperidol increased the number of D2‐receptors but left [125]Bolton‐Hunter‐substance P binding sites, representing neurokinin 1 (NK‐1) receptors, as determined by competition experiments with selective ligands, unchanged. Clozapine (30 mg/kg, i.m.) did not influence nigral and striatal tachykinin tissue levels, preprotachykinin‐A mRNA and potassium‐evoked release or spontaneous efflux in the substantia nigra, or D2‐receptors and [125I]Bolton‐Hunter‐substance P bindin sites. The present data indicate that neuroleptics influence the striato‐nigral tachykinin system in different ways. Tachykinins may therefore, contribute to the therapeutic and/or untoward

ISSN:0887-4476    

DOI:10.1002/syn.890060102

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe mediolateral part of the lateral septal area (LSA) is a common target of hipocamposeptal afferents, neuropeptide containing, catecholaminergic, cholinergic, and GABAergic pericellular baskets of different origins. This specific innervation pattern as well as electrophysiological data concerning this area suggest a convergent input from different sources to particular LSA neuron populations. Light and electron microscopy combined with Golgi impregnation and acute anterograde degeneration techniques following ltransection of the fimbria‐fornix were employed to determine whether LSA neurons with hippocampal input have any characteristic and distinctive morphological signs. About 20% of all Golgi impregnated LSA neurons were found to have somatic spine. All of these somatospiny neurons are synaptic targets of hippocamposeptal fibers. The degenerated hippocamposeptal boutons establish asymmetric synaptic contacts on their soma, somatic and dendritic spines, and on dendritic shafts. Somatospiny neurons located in the most medial and dorsal parts of the LSA seem to project toward the medial septum while all of the others appear to send descending fibers to ventral areas. Somatospiny neuron axons occasionally give out recurrent collaterals. Quantitative analysis on the spatial distribution of the somatospiny neurons revealed that practically all of them are encountered in the mediolateral division of the LSA. This area includes the lateral part of the intermediolateral spptal nucleus and adjacent lateral portions of the dorsolateral and the ventrolateral sptal nucle

ISSN:0887-4476    

DOI:10.1002/syn.890060103

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

年代:1990

数据来源: WILEY

摘要:

AbstractA family of guanine nucleotide binding proteins (G proteins) is involved in the transduction of information from receptors on the cell surface into cellular responses. Two G proteins, Giand Gs, were initially defined by their inhibitory or stimulatory actions on adenylyl cyclase, respectively. In addition, brain contains high levels of another G protein, Go. cDNAs for the alpha subunits for these G proteins have been cloned and sequenced. This allowed us to examine the distributions of the mRNAs for the alpha subunits for Gi, Goand Gs, in the rat brain usingin situhybridization with radio‐labelled, synthetic oligonucleotide probes. Various regions known to contain catecholamine cell groups displayed high levels of G protein mRNA. There is good physiological evidence supporting a role for G proteins in signal transduction in dopaminergic and noradrenergic neurons. Therefore, further experiments were undertaken usingin situhybridization combined with immunohistochemistry to examine G protein expression in identified catecholamine neurons. The results indicate that the dopaminergic neurons of the substantia nigra and the noradrenergic neurons of the locus ceruleus express the mRNA for the alpha subunits of all three of these G proteins. These data provide evidence for the coexpression of multiple G proteins within identified catecholamine neurons in the brai

ISSN:0887-4476    

DOI:10.1002/syn.890060104

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

年代:1990

数据来源: WILEY

摘要:

AbstractFenfluramine is an amphetamine derivative that in humans is used primarily as an anorectic agent in the treatment of obesity. In rats, subchronic high‐dosed, l‐fenfluramine treatment (24 mg/kg subcutaneously, twice daily for 4 days) causes long‐lasting decreases in brain serotonin (5HT), its metabolite 5‐hydroxyindoleacetic acid, and high‐affinity 5HT uptake sites. Moreover, this high‐dose treatment regimen causes both selective long‐lasting decreases in fine‐caliber 5HT‐immunoreactive axons and appearance of other 5HT‐immunoreactive axons with morphology characteristic of degenerating axons. Determination of the potential neurotoxic effects of fenfluramine treatment using immunohistochemistry is limited from the perspectives that staining is difficult to quantify and that it relies on presence of the antigen (in this case 5HT), and the 5HT‐depleting effects of fenfluramine are well known. In the present study, we used quantitativein vitroautoradiography to assess, in detail, the density and regional distribution of [3H]paroxetine‐labeled 5HT and [3H]mazindol‐labeled catecholamine uptake sites in response to the high‐dose fenfluramine treatment described above. Because monoamine uptake sites are concentrated on monoamine‐containing nerve terminals, decreases in uptake site density would provide a quantitative assessment of potential neurotoxicity resulting from this fenfluramine ltreatment regimen. Marked decreases in densities of [3H]paroxetine‐labeled 5HT uptake sites occurred in brain regions in which fenfluramine treatment decreased the density of 5HT ‐like immunostaining when compared to saline‐treated control rats. These included cerebral cortex, caudated putamen, hippocampus, thalam us, land medial hypothalamus. Smaller, but nonetheless significant, decreases in density of [3H]paroxetine‐labeled 5HT uptake sites were noted in brain regions in which partial sparing of 5HT‐like immunoreactive fibers had been reported following fenfluramine treatment, specifically septum, lateral hypothalamus, and amygdala. In contrast, [3H]mazindol autoradiography revealed that total catecholamine (i.e., dopamine and norepinephrine) uptake sites in cerebral cortex, caudate putamen, and locus coeruleus, areas in which [3H]paroxetine‐labeled 5HT uptake sites were significantly decreased, were unaffecterd by this fenfluramine treatment. These data support the hypothesis that subchronic, high‐dose fenfluramine treatment causes selective degeneration of 5HT axons in rat brain. Since pharmacokinetic studies show that the dosing regimen used in this study exposes rat brain to concentrations of fenfluramine that are approximately 600 times greater than those resulting from the therapeutic oral dose, caution must be exe

ISSN:0887-4476    

DOI:10.1002/syn.890060105

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe synaptic organization of septal inputs to the rat habenular complex of the dorsal diencephalon was examined employing the anterograde tracer wheat germ agglutinin conjugated to horseradish peroxidase (WGA‐HRP). The cellular distribution of substance P (sP) and choline acetyltransferase (ChAT) immunoreactivity was also studied at the light and electron microscopic level. Following placements of tracer within the entire septum, labeled axons were observed in the stria medullaris and in the medial and lateral subnuclei of the habenula. Following injections of tracer in the nuclei triangularis and septoffimbrialis of the posterior septum, the medial subnucleus was heavily labeled, whereas the lateral subnucleus was devoid of peroxidase activity. The medial subnucleus possessed labeled myelinated axons and terminals that contained clear, spherical vesicles and formed asymmetric contacts with dendritic spines and shafts. Terminals possessing WGA‐HRP activity also formed non‐synaptic junctions with other labeled or unlabeled terminals. sP and ChAT immunoreactivity in normal and colchicinetreated animals was confined to dendrites and somata within the medial habenula. Terminals containing clear spherical vesicles formed asymmetric synaptic contacts with these immunoreactive somatic and dendritic profiles. Based on the combined anterograde tracing and immunohistochemical data, it is proposed that septal projections provide a direct innervation to habenular neurons that contain ChAT or SP activity. These septal inputs may play an important role in the facilitation of the ChAT‐ and sP‐positive habenular neurons, both of which provide prominent afferent inputs to the interpdeuncular nucleus. Thus, neurons of the habenula and interpeduncular nucleus are under the direct and indirect influence of septal neurons within the limbic forebrai

ISSN:0887-4476    

DOI:10.1002/syn.890060106

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

年代:1990

数据来源: WILEY

摘要:

AbstractA serotonergic input to the lateral cervical nucleus of cats and monkeys (Aotus trivirgatus) was demonstrated with immunohistochemical methods. In both species, the lateral cervical nucleus was found to contain a network of serotoninimmunoreactive fibers. However, the density of labeled fibers was greater in the monkeys than in the cats. Most labeled fibers were thin and had irregularly spaced varicosities. Electron microscopic examination showed that labeled varicosities were in apposition with dendrites, neuronal lsomata and lunlabeled terminals, but synapses were rare.The results demonstrate that the lateral lcervical nucleus receives a serotonergic innervation, as is the case with other somatosensory relay structures such as the spinal dorsal horn and the dorsal column nuclei. The presence of a serotonergic innervation suggests that the transmission of somatosensory information through the lateral cervical nucleus is modulated by a descending pathway. However, its effect on the response properties of neurons in the lateral cervical nucleus in unknown.

ISSN:0887-4476    

DOI:10.1002/syn.890060107

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

年代:1990

数据来源: WILEY

摘要:

AbstractBecause cacaine effectively increases extracellular levels of both dopamine (DA) and serotonin (5HT), it might be expected that this agent would inhibit transmitter biosynthesis in these monoamine neurons by activation of autoregulatory feedback pahwas. This possibility was tested by measuring the effect of cocaine on 3,4‐dihydroxyphenylalanine accumulation (DA synthesis) and 5‐hydroxytryptophan accmulation (5HT synthesis) in vivo and in vitro after inhibition of aromatic amino acid decarboxylase with NSD‐1015. In vivo, cocaine suppressed both Da and 5HT synthesis in a dose‐depentent (10–60 μmol/kg, i.p.) and time‐dependent fashion (maximum 60 min after administrationm, recovery by 120–150 min). Inhibition of Da and 5HT synthesis ranged from 35% to 60% depending on the brian region and was apparent in dopaminergic fields such as the medial prefrontal cortex, nucleus accumbens, piriform cortex, striatum, and in noradrenergic fields such as the hipocampus and temporal cortex. Inhibition of DA, but not 5HT, synthesis was blocked by the D2 antagonist sulpiride in brain areas containing DA nerve terminals. Procaine (30 μmol/kg) did not inhibit DA or 5HT synthesis and prior treatment with reserpine diminished the effectiveness of cocaine in the medial prefrontal cortex, but not in the striatum. Cocaine did not reverse the gamma‐butyrolactone‐induced increase in striatal DA synthesis nor did cocaine block the ability of the D2 agonist quinpirole to reverse the increase. In vitro, cocaine inhibited Da synthesis in depolarized (K+=30 mM) striatal brian slices, an effect that was reversed by the D2 antagonist eticlopride. These results suggest that DA and 5HT neurons compensate in situ for cocaine‐induced increases in synaptic transmitter levels by a transient inhibition of transmitter biosynthesis. Acute suppression of transmitter synthesis (and release) in mesoprefrontal DA neurcns may represent the principal compensatorty mechanism in

ISSN:0887-4476    

DOI:10.1002/syn.890060108

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe new CCKBanalog, Boc‐Tyr (SO3H)‐gNle‐mGly‐Trp‐(NMe)‐Nle‐Asp‐PheNH2(BC 264) exhibited a high affinity (KI = 0.39 ± 0.15 nM) and selectivity for central (B) versus peripheral (A) receptors (KI CCKA/KI CCKB= 910) in the rat. In agreement with these binding studies, BC 264 was at least 50 times more potent than CCK8in stimulating the firing of rat CA hippocampal neurones. Furthermore sterotzxic injection of BC 264 or CCK8in the VTA of rats resulted in potentiation of the dopamine‐induced hypolocomotion. These two types of CCK8responses have been previously shown to involve CCKBreceptrs. In contrast, after administration into the posteor‐median nucleus accumbens, the hypoexploration, the increase of emotionality of rats, or the potentiation of dopamine‐induced hyperlocomotion were obtained after injection of CCK8but not of BC 264, supporting the involvement of peripheral CCKAreceptors in these CCK8responses. Owing to its resistance to peptidases, BC 264 appears to be of great interest in the investigation of the still uncertain funcitonal roles of CCK in the

ISSN:0887-4476    

DOI:10.1002/syn.890060109

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

年代:1990

数据来源: WILEY

摘要:

AbstractNeurotensin is present in high concentrations in the mammalian gut, especially in enteroendocrine cells of the mucose. Exogenous neurotensin has been shown to alter ion transport by the mucosa and contractile activity of intestinal smooth muscle. The purpose of this study was to determine the distribution of neurotensin binding sites withing the intestinal wall. Initially, biochemical characteristics of [125I]neurotensin binding sites were determined within two preparations of the distal porcine jejunum: (1) the mucosa and submucosa, and (2) the circular and longitudinal muscle with their intramural plexuses. Ligand binding data for the preparation including the mucosa and submucosa indicated that [125I]neurotensin bound specifically to two sites having apparent equilibrium dissociation constants of approximately 0.46 and 0.37nM. A binding site with a dissociation constant of approximately 0.38 nM was confirmed for the preparation of muscle and associated intramural plexuses. Xenopsin and neurotensin

ISSN:0887-4476    

DOI:10.1002/syn.890060110

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

年代:1990

数据来源: WILEY

摘要:

AbstractEffects of phorbol ester (PE) (4β‐phorbol‐12,13‐dibutyrate) on transmitter release were studied in the deep extensor neuromuscular system of the prawn,Macrobrachium rosenbergii. Our findings show that PE enhances transmiter release as indicated by an increase in the quantal content. PE had no past‐synaptic effects.The increase in release is accompanied by a slight decline in twin pulse facilitation, suggesting a minor increase in Ca2+entry. The fact that the increase in Ca2+entry has a minor contribution to the PE effect is supported by the following observations: the duration of facilitation was not affected by PE, and 3,4‐diaminopyridine (3,4‐DAP), which by itself increased release, did not reduce the effect of PE. The time course of release was measured from synaptic delay histograms, upon which PE had no effect. The finding indicates that protein kinase C (PKC) is probably not involved in the rate limiting step of the process of secretion. The log/log plot of the initial part of the delay histogram is not affected by PE, suggesting a lach of effect on cooperativity of the release process. Increased release by loading the presynaptic terminal with Ca2+either by pretreatment with Ca2+ionophore or by frequent stimulation prevented further increase in release by PE.We conclude that the main effect of PE is confined to stages of release that are secondary to the first elevation in presynaptic Ca2+. PKC in this system probably plays a role in long term modulation of release, and it can be activated in processes leading to presynaptic Ca2+

ISSN:0887-4476    

DOI:10.1002/syn.890060111

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

年代:1990

数据来源: WILEY