共查询到20条相似文献,搜索用时 0 毫秒
1.
Effects of
Experiments involving single-unit recordings and microiontophoresis were carried out in the barrel cortex of awake, adult rats subjected to whisker pairing, an associative learning paradigm where deflections of the recorded neuron's principle vibrissa (S2) are repeatedly paired with those of a non-adjacent one (S1). Whisker pairing with a 300 ms interstimulus interval was applied to 61 cells. In 23 cases, there was no other manipulation whereas in the remaining 38, pairing occurred in the presence of one of three pharmacological agents previously shown to modulate learning, receptive field plasticity and long-term potentiation: N-methyl-
-aspartic acid (NMDA) (n=8), the NMDA receptor antagonist AP5 (n=17) or the nitric oxide synthase inhibitor
-nitro-arginine-N-methyl-ester (
-NAME) (n=13). Non-associative (unpaired) experiments (n=14) and delivery of pharmacological agents without pairing (n=14) served as controls. Changes in neuronal responsiveness to S1 following one of these procedures were calculated and adjusted relative to changes in the responses to S2. On average, whisker pairing alone yielded a 7% increase in the responses to S1. This enhancement differed significantly from the 17% decrease obtained in the non-associative control condition and could not be attributed to variations in the state of the animals because analysis of the cervical and facial muscle electromyograms revealed that periods of increased muscular activity, reflecting heightened arousal, were infrequent (less than 4% of a complete experiment on average) and occurred randomly. The enhancement of the responses to S1 was further increased when whisker pairing was performed in the presence of
-NAME (27%) or NMDA (35%) whereas AP5 reduced it to 1%. During the delivery period, NMDA enhanced both neuronal excitability and responsiveness to S1 whereas AP5 depressed them. However, the effects of both substances disappeared immediately after administration had ended.
-NAME did not affect the level of ongoing activity and responses to S1 significantly. From these data, we concluded that, since the changes in the responses to S1 lasted longer than the periods of both whisker pairing and drug delivery, they were not residual excitatory or inhibitory drug effects on neuronal excitability. Thus, our results indicate that, relative to the unpaired controls, whisker pairing led to a 24% increase in the responsiveness of barrel cortex neurons to peripheral stimulation and that these changes were modulated by the local application of pharmacological agents that act upon NMDA receptors and pathways involving nitric oxide. We can infer that somatosensory cerebral cortex is one site where plasticity emerges following whisker pairing. 相似文献
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2.
Unique properties of [
In order to investigate possible differences between NMDA receptor-coupled ion channels in the spinal cord and in the cerebral cortex, we have characterized [
]MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine] binding and its regulation by glutamate and glycine in membrane preparations of the rat spinal cord and cerebral cortex. The KD value of [
]MK-801 binding was higher in the spinal cord than in the cerebral cortex, mainly due to a lower association rate constant. When corrected for the concentrations of residual endogenous amino acids, the EC50 values for glycine were lower at spinal NMDA receptors compared to those in the cerebral cortex, whereas the EC50 values for glutamate were similar in both regions. The IC50 values of
-((3)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (
-CPP) were significantly lower in the spinal cord in the presence of saturating concentrations of glutamate. The IC50 values of 7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(H)-quinoline (L-701,324) were significantly lower in the spinal cord under all conditions. These results suggest that NMDA receptors in the spinal cord display low affinity for MK-801, which may correspond to a lower affinity of the voltage-dependent Mg2+ block. Furthermore, NMDA receptors in the spinal cord appear to display high sensitivity to glycine and to glutamate and glycine antagonists. 相似文献
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3.
Neuropeptide Y antibody attenuates 2-deoxy-
2-Deoxy-
-glucose (2-DG) has been shown to induce increased feeding responses in animals. Recent studies suggest the possible involvement of neuropeptide Y (NPY) in 2-DG-induced feeding. The present study examined the effect of immunoneutralization of endogenous NPY on 2-DG-induced feeding. NPY antibody injected into the paraventricular nucleus of the rats significantly attenuated 2-DG-induced feeding, suggesting that hypothalamic NPY may mediate, at least partly, the effect of 2-DG on food intake. 相似文献
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4.
2,5-Anhydro-
Injection of the fructose analogue, 2,5-anhydro-
-mannitol (2,5-AM), stimulates eating behavior in rats. Previous studies have shown that administration of 2,5-AM in doses that elicit eating induces Fos-like immunoreactivity (Fos-li) primarily in hindbrain structures, including the nucleus of the solitary tract (NTS), area postrema (AP), and lateral parabrachial nucleus (PBN). To more closely assess the relationship between neural activation and the eating response to 2,5-AM treatment, we measured food intake and brain Fos-li in rats given a range of doses of 2,5-AM. The numbers of neurons showing Fos-li were quantified by computerized image analysis. Doses of 2,5-AM that reliably stimulated food intake induced Fos-li in both the hindbrain and forebrain, including in the NTS, AP, lateral PBN, central lateral nucleus of the amygdala, dorsal lateral bed nucleus of the stria terminalis (BNSTdl), anterior paraventricular nucleus of the thalamus, supraoptic nucleus, subfornical organ, and paraventricular hypothalamic nuclei. A low dose of 2,5-AM that did not elicit eating increased Fos-li marginally only in the AP, PBN, and BNSTdl. The results suggest that 2,5-AM treatment activates a vagal afferent pathway projecting from the hindbrain to forebrain that is involved in initiating the eating response to the fructose analogue. 相似文献
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5.
Inhibition of NMDA-induced increase in brain temperature by N-ω-nitro-
Shuichi Hara Toshiji Mukai Fumi Kuriiwa Nobuhisa Iwata Takeshi Yanase Sadao Kano Takahiko Endo 《Brain research》1997,756(1-2)
Intracerebroventricular administration of N-methyl-
-aspartate (NMDA) caused an increase in brain temperature, which appeared rapidly and preceded that in rectal temperature, in urethane-anesthetized rats. The increase in brain temperature was divided into two phases, an early increase and a late increase. Intracerebroventricular indomethacin, a cyclooxygenase inhibitor, completely abolished the NMDA-induced late increase, but not the early increase, in brain temperature. On the other hand, intracerebroventricular N-ω-nitro-
-arginine, a potent inhibitor of nitric oxide synthase, strongly suppressed both the early and the late increases. These findings suggest that both nitric oxide and prostaglandins may be involved in the increase in brain temperature after NMDA receptor activation. 相似文献
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6.
Characterization of [
Coated vesicles prepared from bovine brain cerebral cortex exhibited [
]5-hydroxytryptamine (5-HT, serotonin) and [
]spiperone binding activities. The binding activities were localized in the inner core vesicles. Binding reached an equilibrium level by 30–45 min at 30°C, and was reversed by the addition of 100 μM 5-HT for [
]5-HT binding or 10 μM ketanserin for [
]spiperone binding. The saturation binding experiments indicated a single class of binding sites for [
]5-HT and [
]spiperone with apparent Kd values of 2.4 and 1.75 nM, respectively. The binding of [
]5-HT was displaced by 5-HT and 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), but not by ketanserin. The binding of [
]spiperone was displaced by spiperone and ketanserin but not by 5-HT or 8-OH-DPAT even at 1 mM. The coated vesicles were shown by immunoblotting assay to contain α-subunits of GTP-binding proteins, Gαs, Gαi2, Gαi3, Gαo and Gαq/11. Forskolin-stimulated adenylate cyclase activity in the coated vesicles was inhibited to 80% of the control level by 5-HT or 8-OH-DPAT. These results suggested that 5-HT1A and 5-HT2A receptors are present in bovine brain coated vesicles and that the 5-HT1A receptors are coupled to adenylate cyclase activity via GTP binding proteins. 相似文献
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7.
Modulatory effect of
We investigated whether NG-nitro-
-arginine methyl ester (
-NAME), a specific inhibitor of nitric oxide synthase (NOS), can modify the stress-induced adrenocorticotropic hormone (ACTH) and corticosterone responses, because we found that immobilization-induced stress increases NOS mRNA and protein levels and enzyme activity in the adrenal cortex. The physiological significance of these phenomena, however, remains unknown. Plasma ACTH and corticosterone levels were determined by radioimmunoassay (RIA) of systemic blood samples and NOS enzyme activity was measured as the rate of [3H]arginine conversion to [3H]citrulline in the presence of tissue homogenate of adrenal cortex separated from the adrenal gland. The NOS enzyme activity in the adrenal cortex of rats pre-injected with saline at 2 h after the 2-h immobilization was significantly higher (P<0.01) than that in the non-stressed controls. Pre-injection of
-NAME (100 mg/kg, s.c.) almost completely abolished the activity. This dose of
-NAME maintained a significantly elevated plasma corticosterone level (P<0.05, compared with basal level) even 2 h after the 2-h stress, whereas the plasma corticosterone level in rats pre-injected with saline returned to the basal level at the same time point. Plasma ACTH level in
-NAME-pre-treated rats was higher than that in those pre-treated with saline 2 h after the stress, but the difference was not significant. This dose of
-NAME did not influence plasma ACTH or corticosterone levels under resting conditions without stress. These findings suggest that the stress-induced increase in NO synthesis in the adrenal cortex can modify the stress-induced corticosterone response to facilitate the recovery from the elevated corticosterone secretion by stress in the adrenal cortex to the resting basal level. 相似文献
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8.
Monoamine oxidase-dependent metabolism of dopamine in the striatum and substantia nigra of
Donato A. Di Monte Louis E. DeLanney Ian Irwin Joyce E. Royland Piu Chan Michael W. Jakowec J. William Langston 《Brain research》1996,738(1)
The effects of monoamine oxidase (MAO) inhibitors on the metabolism of dopamine synthesized from exogenous
-DOPA were investigated in the striatum and substantia nigra of squirrel monkeys. Administration of a single dose of
-DOPA (methyl ester, 40 mg/kg, i.p.) caused a significant increase in the levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and in the DOPAC/dopamine ratio in the putamen, caudate and substantia nigra. These changes were more pronounced in the substantia nigra than in the striatum and within the striatum of
-DOPA-treated monkeys, levels of dopamine and its metabolites were higher in the putamen than in the caudate nucleus. When
-DOPA treatment was preceded by the injection of clorgyline or deprenyl at a concentration (1 mg/kg) which selectively inhibited MAO A or MAO B, respectively, striatal dopamine was increased while the striatal DOPAC and HVA levels and DOPAC/dopamine ratio were significantly reduced as compared to the values obtained with
-DOPA alone. The two MAO inhibitors also counteracted the increase in the DOPAC and HVA levels and DOPAC/dopamine ratio induced by
-DOPA in the substantia nigra. Thus, both MAO A and MAO B contribute to the metabolism of dopamine when higher levels of this neurotransmitter are generated from
-DOPA in the squirrel monkey. The extent of reduction of dopamine catabolism (as assessed by the decrease in DOPAC and HVA levels) in the striatum and substantia nigra was similar with clorgyline and deprenyl even if the ratio MAO A/MAO B was approximately 1 to 10. This indicates that, though catalyzed by both MAO A and MAO B, dopamine deamination following treatment with
-DOPA preferentially involves MAO A. 相似文献
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9.
Repeated, intermittent administration of psychostimulants produces an enhancement of the subsequent behavioral effects of these drugs. This behavioral sensitization has been implicated in maintenance of and relapse to drug-taking. As a result, there has been great interest in elucidating the mechanisms underlying both the development and expression of sensitization. An accumulation of data from studies of stimulant-induced locomotor activity has implicated excitatory amino acids in the development of behavioral sensitization. In the present study, N-methyl-
-aspartate (NMDA) (0.6, 1.25 or 2.5 μg) infused bilaterally into the ventral tegmental area (VTA) produced dose-dependent locomotor activation. The locomotor activating effect of NMDA was increased following repeated NMDA administration (two exposures to intra-VTA NMDA), suggesting sensitization. However, repeated intra-VTA NMDA failed to sensitize rats to the locomotor activating effects of systemically administered cocaine (5.0, 10.0 or 20.0 mg/kg). These findings are consistent with the notion that repeated activation of NMDA receptors is sufficient for the development of behavioral sensitization to NMDA. Other neuroadaptations produced by repeated psychostimulant administration are required in order for the development of sensitization to the behavioral effects of those drugs. 相似文献
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10.
Guylaine Mateu Alain Privat Jean Thibault Jacques Vignon 《International journal of developmental neuroscience》1997,15(7):637
Excitotoxicitiesof glutamate and NMDA were studied on primary cultures of rat embryonic substantia nigra. The toxicity of the general neuronal population (identified with neuron specific enolase-NSE) was compared with that of dopaminergic neurons (identified with TH antibodies).We have shown that there exists a time-dependent toxicity to glutamate in 9 d old cultures in vitro and exposures as short as 5 min are significantly toxic. By comparing the effects of long time exposures (24 h) to NMDA and glutamate, we can show dose-dependent toxicity ; however NMDA shows a less marked effect, especially at high doses (>500–1000 μM) as opposed to less potent lower doses (<500 μM).In comparison to the general population of NSE-positive mesencephalic neurons, TH-positive neurons seem to exhibit a similar vulnerability to EAA. The fact that TH-positive neurons are only partially protected against glutamate toxicity by the non-competitive NMDA antagonist TCP indicates that they are more susceptible to non-NMDA mediated neurotoxicity than the general neuronal population. 相似文献
11.
Nitric oxide (NO) has been proposed to trigger long-term potentiation (LTP) at CA3 to CA1 synapses. We previously reported that NO synthesis inhibitors and blockers reduce an electrophysiological index of NMDA receptor activation in acute hippocampal slices. We now show that the NOS inhibitor, NG-methyl-
-arginine (MLA), also reversibly prevents LTP induction in organotypic hippocampal slices and significantly reduces a biochemical index of NMDA receptor function. These results further indicate that MLA inhibits LTP induction by interfering with NMDA receptor functions. 相似文献
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12.
This study investigated the anticataleptic activity of MK-801 versus the D1 antagonist SCH 23390 and the D2 antagonist raclopride, using the horizontal bar test in the rat. MK-801, 0.2 mg/kg i.p., strongly opposed the cataleptogenic actions of SCH 23390 and raclopride administered systemically (1 and 3 mg/kg i.p., respectively), or directly into the corpus striatum (CS) or nucleus accumbens (NAc; 1 and 10 μg, respectively). Conversely, intraCS and intraNAc pretreatment with MK-801 (10 μg) markedly attenuated the cataleptic response to a systemic injection of SCH 23390 or raclopride. In the latter experiments the anticataleptic effect of MK-801 was pronounced and sustained (>2 h), except with intraCS MK-801 versus raclopride, where it was initially profound but only short-lived (15 min). Stereotaxic injection of MK-801 (1 μg) into the substantia nigra pars reticulata (SNr) prevented catalepsy developing to either dopamine D1 or D2 receptor antagonism. These results indicate there must be unimpeded glutamate neurotransmission in the CS and NAc before catalepsy can develop fully to D1 and D2 dopamine receptor blockade in these structures. The weaker glutamate–D2 interaction in the CS than in the NAc may be related to differences in the N-methyl-
-aspartate receptor subpopulations in these nuclei. Finally, the ability of intranigral MK-801 to diminish both D1- and D2-dependent catalepsy suggests the SNr acts as a common output pathway for the expression of both forms of catalepsy in the rat. 相似文献
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13.
The activity and regional distribution of
-amino acid oxidase (DAO), an enzyme that inactivates
-serine, were examined in the medulla and spinal cord of the rat by biochemical and histochemical procedures. DAO activity was noticeably low or absent in the nucleus of the solitary tract, ventrolateral medulla and intramediolateral cell column of the spinal cord. This may be indicative of a neuromodulatory role for endogenous
-serine (at the NMDA-glycine site) in the central control of blood pressure. 相似文献
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14.
Previous studies in our laboratory have demonstrated that microinjection of N-methyl-
-aspartate (NMDA) agonist into the nucleus magnocellularis (NMC) of the medial medulla increases muscle tone and/or produces locomotion, while injection of corticotropin-releasing factor (CRF) and non-NMDA agonists into the same or nearby sites suppresses muscle tone. In the first paper of this series, we report that myoclonic twitches or coordinated rhythmic leg movement (locomotion) can be induced by either NMDA or hemorrhagic bilateral lesion of the ventral mesopontine junction (vMPJ). In this paper, we report that microinjection of CRF (10 nM) or non-NMDA agonists, kainic acid (0.1–0.2 mM) and quisqualic acid (1–10 mM), into the NMC block locomotion and myoclonic twitches. The latency and duration of CRF and non-NMDA agonist-induced blockade of motor activity were short, at 34 s and 3.6 min, respectively. However, microinjection of the NMDA antagonists
-2-amino-5-phosphonovaleric acid (APV; 50 mM) or
-2-amino-5-phosphonopentanoic acid (AP5, 20 mM) block myoclonus at a latency of 0.6–3 min with the block lasting for a mean of 7 h. Thus, activation of non-NMDA receptors or inactivation of NMDA receptors in NMC can block myoclonus. An imbalance between the inputs to these receptor systems may contribute to the generation of abnormal motor activation in waking and sleep. 相似文献
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15.
Since ATP has been reported to be a potent excitatory transmitter in the mammalian central nervous system (CNS), we studied the neurochemical characters of the binding sites of
,
-methylene ATP, an agonist of P2X receptors, in mouse crude synaptic membranes. ATP and its related compounds inhibited [3H]
,
-methylene ATP binding in a concentration-dependent manner. The potency order in the inhibition of the binding was as follows;
,
-methylene
>
> ATP ≥ ADP >
,
-methylene ATP UTP > 2-methylthio ATP. And adenosine did not affect the binding. The order was different from those reported in peripheral tissues. And Sr2+, Ca2+, Mg2+, and Cd2+ enhanced the binding. These results suggest that
,
-methylene ATP binding sites in CNS have different characters from those in peripheral tissues. 相似文献
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16.
Takehiko Maeda Neng-neng Cheng Toshiaki Kume Satoshi Kaneko Hanae Kouchiyama Akinori Akaike Mutsuaki Ueda Masamichi Satoh Yoshio Goshima Yoshimi Misu 《Brain research》1997,771(1):259
The exposure of cultured rat striatal neurons to
-DOPA caused marked cell death. The
-DOPA cytotoxicity was inhibited by the addition of Mg2+ to and by the removal of Ca2+ from the culture medium, and also by the application of tetrodotoxin. Moreover, prolonged application of
-DOPA increased the glutamate content in the culture medium. These results indicate that
-DOPA produces neurotoxicity by facilitating glutamate release. 相似文献
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17.
Polyamines play critical roles during the development of brain neurons. In the present study we examined the effects of polyamines on neuronal apoptotic death. Rat cerebellar granule neurons were cultured in the presence of a depolarizing concentration of KCl (25 mM) in the medium. Apoptotic neuronal death was induced by changing the medium to that containing 5.6 mM KCl without serum. Spermine as well as spermidine and putrescine prevented cell death in a concentration-dependent manner with the order of potency being spermine>spermidine>putrescine. The effect of spermine was partially blocked by several NMDA-type glutamate receptor antagonists including (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801). MK-801-sensitive neuroprotection by spermine depended on cell density. Activation of CPP32 (caspase-3/Yama/apopain)-like proteolytic activity, a key mediator of apoptosis, precedes neuronal death, and polyamines prevented an increase in this activity. These results demonstrate that polyamines protect neurons from apoptotic cell death through both NMDA receptor-dependent and -independent mechanisms, acting upstream from the activation of CPP32-like protease(s). © 1997 Elsevier Science B.V. All rights reserved. 相似文献
18.
Chronic pain may result from hyperexcitability following activation of spinal NMDA receptors. A naturally-derived mammalian peptide, histogranin, may possess NMDA antagonist activity. This study explored the possibility that stable analog [Ser1]Histogranin (SHG) could reduce chronic pain. Neuropathic pain was induced using the chronic constriction injury model (CCI). Intrathecal injection of SHG markedly attenuated the hyperalgesia and allodynia resulting from CCI, nearly normalizing responses. These results suggest that the natural peptide histogranin may be a novel adjunct in neuropathic pain management. 相似文献
19.
Interferon-
The influence of recombinant interferon-
(rIFN-
) on the development of acetylcholine receptor (AChR) aggregates in cocultures of rat embryonic muscle cells and spinal cord neurons was studied by counting the number of AChR aggregates in relation to cholinergic nerve fibers coming to the muscle fibers. rIFN-
caused no decrease in the number of cholinergic nerve fibers, but inhibited the increase in the number of AChR aggregates that occurs early during cocultivation and is an early sign in the development of neuromuscular junctions. rIFN-
stimulated release of nitric oxide, but no effects on aggregation of AChRs occurred after exposure to a nitric oxide synthase inhibitor,
-NG-monomethylarginine, or by the addition of nitroprusside, a generator of nitric oxide. No effect was seen on the number of AChR aggregates when the cultures were exposed to rIFN-
at later time points of cocultivation, when the increase in number of AChRs had already occurred. These studies indicate that the key immunoregulatory cytokine IFN-
can cause alterations in the early process of synapse formation and that these effects are independent of the nitric oxide release caused by the cytokine. 相似文献
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20.
Ultrastructural immunocytochemical localization of the N-methyl-
The N-methyl-
-aspartate (NMDA)-type glutamate receptors in the shell region of the nucleus accumbens (ACB) have been implicated in the modulation of dopamine release and in amphetamine-induced neurotoxicity. We used electron microscopic immunocytochemistry to determine the anatomical sites for NMDA-mediated effects of glutamate and for their potential interactions with dopaminergic afferents identified by the presence of tyrosine hydroxylase (TH) in this region of the rat brain. Immunogold and immunoperoxidase methods were used to localize antisera against the R1 subunit of the NMDA receptor (NMDAR1) alone or combined with TH. In single labeling experiments, approximately half of the NMDAR1-like immunoreactivity (NMDAR1-LI) was localized to extrasynaptic plasma membranes of neuronal processes, many (92 out of 215) of which were dendrites, and only 33 out of 215 were unmyelinated axons or terminals. Surprisingly, the neuronal labeling of NMDAR1 was almost equaled by that seen in astrocytic processes (88 out of 215). Dual labeling for TH and NMDAR1 was rarely observed and was only seen in axons. However, in favorable planes of section, NMDAR1 was noted along intervaricose segments of axons in which TH was more readily seen in the varicosity. This differential intra-axonal distribution suggests an underestimation of dual labeling in single coronal sections through unmyelinated axons and terminals. The TH-immunoreactive terminals were more often seen apposed to NMDA-immunoreactive astrocytic processes and dendrites. These results provide the first ultrastructural evidence for presynaptic modulation of dopamine release by NMDA receptors in the shell of the nucleus accumbens. They also indicate that NMDA receptors modulate postsynaptic neurons receiving input from the dopaminergic afferents and suggest a previously unsuspected functional association involving glial NMDA receptors and dopaminergic afferents in this brain region. 相似文献
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