摘要:

AbstractThe effects of acute i. v. administration of severalsigmaligands on the single‐unit activity of nigrostriatal and mesoaccumbal dopaminergic (DA) neurons were evaluated in chloral hydrate‐anesthetized rats. DTG (1, 3‐di(o‐tolyl)guanidine) did not alter DA neuronal activity at nontoxic doses and JO 1784 [(+)‐N‐cyclopropylmethyl‐N‐methyl‐1, 4‐diphenyl‐1‐ethylbut‐3‐en‐1‐ylamine] was inactive. (+)‐Pentazocine was more effective in increasing mesoaccumbal vs. nigrostriatal DA cell firing rates. BMY 14802(α‐(4‐fluorophenyl)‐4‐(5‐fluoro‐2‐pyrimidinyl)‐1‐piperazine‐butanol) dose‐dependently increased DA cell firing rate in both populations. The inhibition of nigrostriatal DA cell firing rate by (+)‐3‐(3‐hydroxyphenyl)‐N‐(1‐propyl)piperidine [(+)‐3‐PPP]was reversed by(−)‐eticlopride and (+)‐but not (−)‐butaclamol, which supports previous evidence that (+)‐3‐PPP‐induced inhibition is due to the DA agonist properties of the drug. From what is known of the pharmacological properties of these compounds, it is concluded that acutesigmareceptor occupation does not markedly alter the firing rate of DA neurons. The dose‐response curve for inhibition of nigrostriatal DA neuronal activity by the D2 DA agonist, quinpirole, was shifted to the right tenfold by BMY 14802 pretreatment (8mg/kg, i. v.) and twofold by (+)‐pentazocine (8 mg/kg, i. v.), but was not changed by DTG (2 mg/kg, i. v.). It is concluded that the marked effects of certainsigmaligands

ISSN:0887-4476    

DOI:10.1002/syn.890110402

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

年代:1992

数据来源: WILEY

摘要:

AbstractIt has been known for some time that perforated synapses increase in number and size with increasing age. Initially, these trends were used to support the concept that nonperforated synapses anlarge until an optimal size is reached, at which point they perforate and may subsequently split. More recent stereological and threedimensional reconstruction investigations, however, suggest that this may not be the case and that perforated and nonperforated synapses constitute separate synaptic populations. In order to test the separate population hypothesis, synapses have been studied ultrastructurally in the parietal cortex of rats aged 19 and 20 days gestation, and 1 and 4 days postnatal. By examining synapses serially, and also by studying three‐dimensional reconstructions, it has been demonstrated that perforated synapses are present at each of these ages. Some are relatively simple in organization, resembling previously described perforated synapses at 14 days of age, although others appear to consist of two or more separate PSD components. These findings demonstrate that perforated synapses are present from early on in synaptogenesis and that developing perforated synapses are present from early on in synaptogenesis and that developing perforated synapses may have distinct characteristics that cast light on their developmental course. © Wiley‐Liss,

ISSN:0887-4476    

DOI:10.1002/syn.890110403

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe neurotoxicity of methamphetamine to monoaminergic neurons was examined. Neurotoxicity was assessed by quantitative autoradiography using radioligands specific for binding to norepinephrine, dopamine, and serotonin uptake sites. High‐dose administration of methamphetamine led to decreases in binding to uptake sites for the three monoamines. Norepinephrine binding sites were decreased in certain amygdaloid nuclei and in the dorsomedial hypothalamic nucleus. Serotonin binding sites were reduced in widespread brain areas, while dopamine binding sites were reduced in the caudate putamen, olfactory tubercle, and nucleus accumbens. The decreases in binding site density for the three monoamines are limited to terminal field areas; cell body areas are not affected. Our results indicate that methamphetamine is neurotoxic to serotonin, dopamine, and norepinephrine neurons. The neurotoxicity to norepinephrine neurons is in selected brain areas. © Wiley‐Liss,

ISSN:0887-4476    

DOI:10.1002/syn.890110404

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

年代:1992

数据来源: WILEY

摘要:

AbstractDopamine (DA)‐containing neurons in primary dissociated cell cultures derived from the embryonic mouse mesencephalon (day E13) were studied by histochemical and electrophysiological techniques. DA neurons exhibited two distinct morphologies, fusiform and multipolar, tended to reside in groups and organize dendrited into common fascicles. While these neurons expressed the cell‐surface marker acetylcholinesterase, the presence of this enzyme could not be used to identify DA neurons unequivocally, since it was also observed in nondopaminergic cells. Neurons were therefore identified as DA by their distinct morphology, and this identification was validated with a double‐labeling procedure that entailed the intracellular deposition of a fluorescent dye (Lucifer yellow or ethidium bromide), followed by processing for tyrosine hydroxylase immunocytochemistry. DA neurons identified in this manner were observed to have resting membrane potentials between − 50 and − 75 m V, input resistances of 50–360 Mω, and membrane time constants of 4.1–14.1 msec. Forty‐seven percent of these cells displayed spontaneous activity that was irregular in nature and often contained bursts (burst length was between two and six action potentials). The DA neurons displayed a variety of ionic conductances, including (1) a Na+conductance (gNa) that underlies the action potential, (2) Ca2+conductances (gCa) that mediate the nonsomatic low‐ and high‐threshold spikes observed, and (3) at least three K+conductances (gk). Voltage‐clamp analysis revealed several distinct transmembrane ionic currents, including (1) a large, rapidly inactivating tetrodotoxin‐sensitive inward Na+current (Na), (2) a 4‐aminopyridine‐sensitive, transient early outward K+current that required a conditioning hyperpolarization of the membrane to be activated by a subsequent depolarization (A‐current, IA), (3) a slowly developing inward current that was seen only after a conditioning hyperpolarization of the membrane and that was dependent on the presence of external Ca2+ions (ICa), and (4) a late‐onset, noninactivating K+current. Between 25% and 54% of the late‐onset K+current was Ca2+‐dependent and was not affected by tetraethylammonium ions. This current was termed IAHP.The remaining current was not sensitive to changes in the extracellular Ca2+concentration but was blocked by external tetraethylammonium ions. This current was termed IK. The direct pressure application of DA (1–200 μM) onto the soma dose‐dependently hyperpolarized these neurons; this effect was potentiated by the presence of the catecholamine reuptake blocker cocaine hydrochloride (10–200 μM). Under voltage‐clamp conditions, DA was observed to increase IK, significantly and had little effect on IAHP. Thus, DA neurons in monolayer cultures were shown to have many of the electrophysiological properties routinely observed for these cells in vivo indicating that this preparation may serve as a useful model system for the further study of the molecular biology of these catec

ISSN:0887-4476    

DOI:10.1002/syn.890110405

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

年代:1992

数据来源: WILEY

摘要:

AbstractLong‐term potentiation (LTP) can be induced in the lateral and basolateral amygdala by stimulating synaptic afferents in the external capsule (EC). We examined the sensitivity of amygdaloid LTP to the NMDA receptor antagonist 2‐amino‐5‐phosphonopentanoate (AP5), which is known to block LTP induction in the Schaffer collateral/CA1 synapses in the hippocampus. While relatively high concentrations (100 μM) ofDL‐AP5 were effective in preventing LTP induction in the lateral and basolateral amygdala in vitro, the same concentrations also significantly depressed synaptic responses to low‐frequency stimulation. Furthermore, at 50 μM, a concentration sufficient to block both synaptic responses mediated by NMDA receptors and LTP induction in the hippocampus and neocortex, AP5 did not affect the probability of inducing LTP in the amygdala. Application of 10 μM 6‐cyano‐7‐nitroquinoxaline‐2, 3‐dione (CNQX), which blocks non‐NMDA excitatory amino acid receptors, reduced the monosynaptic response to EC stimulation by 85%. The remaining CNQX‐insensitive response did not appear to be mediated by NMDA‐type receptors, since it was not reduced by 50 or 100 μM AP5, and showed none of the voltage sensitivity characteristic of NMDA responses. These data suggest that while the induction of LTP in the amygdala produced by EC stimulation is blocked by high doses of AP5, plasticity at these synapses probably does not require activation of NM

ISSN:0887-4476    

DOI:10.1002/syn.890110406

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

年代:1992

数据来源: WILEY

摘要:

AbstractSeveral lines of evidence have suggested there may be a physiologically relevant form of synergistic interaction between D‐1 and D‐2 dopamine (DA) receptors located on postsynaptic neurons in the forebrain that receive a dopaminergic innervation. Because of the theoretical importance of such an interaction with respect to understanding the normal physiology of dopaminergic systems, we evaluated effects of D‐1 and D‐2 selective, agonists, applied microiontophoretically, on the spontaneous electrical activity of a single, identifiable subpopulation of neurons within the caudate nucleus, the type I striatal neuron, in locally anesthetized, gallamine‐paralyzed rats. It was observed that the D‐2 receptor agonist quinpirole (QUIN) produced biphasic effects on cell firing rate. Low ejection currents significantly increased firing rate, while higher currents produced an inhibition. Similar effects were observed for the D‐1 agonists SKF 38393; however, the overall excitations observed at low ejection currents were far less than those observed for QUIN. When these two agonists were applied concurrently, a simple additive effect (but not synergism) was always observed. The acute reduction of striatal levels of DA, by as much as 84% (with pretreatment with α‐methyl‐p‐tyrosine, AMPT), did not alter the responsiveness of type I striatal neurons to the DA receptor agonists applied alone or in combination. These observed effects were not altered either by chloral hydrate anesthesia (in which glutamate‐driven activity was studied) or by a more severe depletion of striatal DA levels (98% depletion produced by combined pretreatment with AMPT and reserpi

ISSN:0887-4476    

DOI:10.1002/syn.890110407

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe responses of human neocortical neurons to iontophoretic application of excitatory amino acids and their modulation by dopamine (DA) were studied in vitro. Brain slices were obtained from children undergoing surgery for intractable epilepsy. Application of N‐methyl‐D‐aspartate (NMDA) to the slices induced slow depolarizations accompanied by decreased input conductances and sustained action potentials in cortical neurons. Glutamate produced rapid depolarizations and firing with few changes in input conductances. Quisqualate also induced depolarization and firing, but input conductances increased during the rising phase of the membrane depolarization. Iontophoretic application of DA alone produced no change in membrane potential or input conductance. However, when DA was applied in conjunction with the excitatory amino acids, it produced contrasting effects. With either bath application of DA or when iontophoresis of DA preceded application of NMDA, the amplitude of the membrane depolarizations and the number of action potentials were increased, whereas the latency of these responses decreased. In contrast, DA decreased the amplitude of the depolarizations and the number of action potentials evoked by glutamate or quisqualate. The fact that DA affects responses to NMDA and glutamate or quisqualate in opposite directions is of considerable importance to the understanding of cellular mechanisms of neuromodulation and the role of DA in cognitive processing and in epilepsy. © Wiley‐L

ISSN:0887-4476    

DOI:10.1002/syn.890110408

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.890110409

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

年代:1992

数据来源: WILEY

摘要:

AbstractSodium salicylate was infused through a microdialysis probe placed in the striatum of anesthetized rats in order to assay the formation of hydroxyl radical (.OH) in the extracellular fluid in vivo. In addition to causing sustained dopamine relese, intrastriatal infusion of the 2′‐methyl analog of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropridine (2′CH3‐MPTP) increased the formation of 2,3‐dihydroxybenzoic acid (2,3‐DHBA), the nonenzymatic. OH adduct of salicylate in the brain dialysate. Inhibition of monoamine oxidase (MAO) by clorgyline and deprenyl completely blocked the formation of 2,3‐DHBA and the sustained dopamine overflow induced by 2′‐CH3‐MPTP. The results indicate that the enhanced formation of cytotoxic. OH by 2′‐CH3‐MPTP is suppressed by MAO inhibitors. These data support the hypothesis that the protective effect of MAO inhibitors on the neurotoxicity induced by MPTP analogues may be due not only to the inhibition of MPTP metabolism by MAO but also the blockade of the formation of OH free radicals. An enhanced generation of cytotoxic. OH free radicals in the striatum which in turn leads to oxidant damage may be relevant to the development of parkinsonism‐like changes in animals produced

ISSN:0887-4476    

DOI:10.1002/syn.890110410

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.890110401

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

年代:1992

数据来源: WILEY