摘要:

BINDING of the D2-like (D2/D3/D4) radioligand [3H]nemonapride under selective conditions (with 300 nM S[−]-raclopride and other masking agents to occlude D2/D3receptors and non-specific binding sites) revealed a subset of raclopride-insensitive binding sites considered D4-like receptors. These sites were stereoselective to R(−)−N-n-propylnorapomorphine (NPA) over its S(+)-NPA in a similar fashion to cloned D4receptors expressed in cell lines. In addition, the highly D4-selective agent L-745,870 displaced 74–83% of these sites in rat brain regions, suggesting that most were D4receptors. These apparent D4receptors represented a relatively high proportion of D2-like receptors in hippocampus, dorsolateral frontal, medial prefrontal and entorhinal cortex, but fewer in caudate-putamen and nucleus accumbens.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PLASTICITY in the central nervous system may play an important role in clinical pain. The present study shows that long-term potentiation (LTP) may be induced in single wide dynamic range (WDR) neurons in the dorsal horn after high-frequency stimulation of the sciatic nerve in intact urethane anaesthetized rats. Extracellular recordings of firing responses after single pulse stimuli were made. The high-frequency conditioning stimulus increased the Aβ and C-fibre-mediated firing responses to single pulse stimuli by 60 and 130%, respectively, for more than 6 h. This finding supports a role for WDR neurons in ‘nociceptive memory' in the dorsal horn. The model presented here may be an important tool for further investigations of mechanisms of plasticity within the dorsal horn.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ORPHANIN FQ or nociceptin (OFQ/N1-17) is a recently discovered peptide which, upon intracerebroventricular administration, reverses opioid-mediated analgesias. OFQ/N1-17terminals are located in the periaqueductal gray (PAG), a structure known to be involved in pain modulation, suggesting that the functional anti-opioid effects of OFQ/N1-17are mediated by PAG neurons. To test this, subsequent microinjections of morphine or kainic acid and OFQ/N1–17were made into the PAG of awake rats. Administration of OFQ/N1–17attenuated the tail flick inhibition produced by both morphine and kainic acid microinjection. OFQ/N1-17attenuation of antinociception produced by a neuroexcitant indicates that OFQ/N1-17reverses opioid antinociception by inhibiting PAG output neurons.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

THE present study investigated the presence, possible synthesis and release of catecholamines (CA) by human amniotic epithelial cells (HAEC) using HPLC with electrochemical detection. The presence of CA was indicated by the detection of norepinephrine (NE), dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in extracts of cultured HAEC. Incubation of HAE cells in medium supplemented with l-tyrosine (CA precursor) and tetrahydrobiopterin (tyrosine hydroxylase cofactor) significantly increased the production of catecholamines, suggesting CA synthesis by HAEC. In contrast, pharmacological inhibition of tyrosine hydroxylase by α-methyl-p-tyrosine (MPT) significantly reduced CA production, further confirming CA synthesis by HAEC. Catecholamines were also detected in the cell incubation media, demonstrating the ability of HAEC to spontaneously secrete CA. Moreover, incubation of cells with 50 mM K+for 10 min increased the amount of CA released into the medium. Additionally, the detection of DOPAC, a primary metabolite of DA, in HAEC strongly indicates that these cells contain DA metabolizing enzymes. The present results suggest that HAEC synthesize and release CA. These cells may be a possible candidate for transplantation therapy of neurodegenerative diseases such as Parkinson's disease and also may serve as a model to study the aspects of catecholaminergic activity.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

THE identification of neurotrophic factors ameliorating secondary neuronal death in the mammalian CNS has raised hopes for improved treatment strategies in neurodegenerative diseases, CNS trauma and ischemia. Glial cell-line derived neurotrophic factor (GDNF) has potent neuroprotective properties in both the CNS and PNS. We sought to investigate whether GDNF exerts survival promoting effects on axotomized retinal ganglion cells (RGCs) in the adult ratin vivo. Transection of the optic nerve induces delayed retrograde death of ∼85% of RGCs within 14 days. Intraocular GDNF rescued 21% of the RGCs which would otherwise have died after axotomy (34% of the normal control population), thereby extending the group of neuronal populations responsive to GDNF.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

RECOMBINANT α1δ2α2LGABAAreceptor channels, transiently expressed in HEK 293 cells, were investigated using the patch-clamp technique in combination with a device for ultra-fast solution exchange. The dose–response relationship revealed an EC50of 11.6 ± 0.9 μM and saturated with 3 mM GABA. The slope between 0.001 and 0.01 mM GABA was 2.2 ± 0.4, indicating at least three binding sites for GABA. The rise time decreased from about 120 ms at 0.001 mM GABA to about 0.8 ms at 10 mM GABA. Single channel openings were grouped in bursts with an average duration of 10.3 ± 3.0 ms. More than 95% of the current was represented by a single channel slope conductance of about 29 pS.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

CHRONOMETRIC and neurophysiological studies have demonstrated that mentally transforming the intended direction of a pointing movement is a time-consuming process, the duration of which increases with the angle of rotation. If the same time-consuming process occurred while tracing a curved trajectory, it would affect the time course of the movement. The data from subjects drawing simple figures match well the predictions made, and support the hypothesis that a time-consuming process of transformation of the intended movement direction operates during the production of continuous trajectories. This biologically inspired hypothesis provides a functional explanation for the relation between speed of the movement and curvature of the path. In addition, it contrasts with the view of continuous movements as essentially oscillatory motions.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

THE aim of this study was to examine and delineate the differences in adrenergic sensitivity of mechanical allodynic behavior among various strains of rats. Neuropathic injury was produced by tight ligation of the L5 and L6 spinal nerves in several strains of rats. The degree of mechanical allodynic behavior was estimated by measuring the mechanical threshold for paw flinching with von Frey filaments. Adrenergic sensitivity of the allodynic behavior was resolved by measuring changes of the mechanical threshold after intraperitoneal injection of phentolamine, an α-adrenergic receptor antagonist. Injection of phentolamine caused a significant but small increase in the thresholds for paw flinching in rats of most of the tested strains; however, in Lewis rats, the resulting threshold increase was extensive enough to eliminate allodynic behavior almost completely. It is concluded that there is a difference in adrenergic sensitivity to mechanical allodynic behavior among different strains of neuropathic rats. In particular, rats of the Lewis strain were extremely sensitive to systemic injection of an α-adrenergic receptor blocker.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

THE activation of complement by β-amyloid (Ab) has been implicated in the local inflammatory response in Alzheimer's disease. To assess the structural parameters required for this activation, β-sheet-containing fibrils of Ab1-28 were induced by low pH and then chemically cross-linked to constrain the β-sheet conformation. Chimeric Abpeptides with a substituted C-terminal sequence derived from two different transmembrane proteins were also assessed for the ability to form fibrils rich in β-sheet structure and to activate complement. Both the cross-linked Ab1-28 and the chimeric Aβ peptides were strong activators of the classical complement pathway. These results suggest that the C-terminal residues (29–42) of Abfacilitate fibril assembly required for complement activation but do not contain the interaction sites required for complement activation, further supporting the hypothesis that C1q binds to the N-terminal hydrophilic domain of Ab, and that a fibrillar β-sheet-rich conformation is required for effective binding and activation of C1.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

IT has been proposed that homozygosity for the apolipoprotein E (apoE) ε4 allele decreases the probability of an individual with Down's syndrome (DS) surviving to adulthood. We performed a meta-analysis of 11 published DS series for which apoE genotype data were available. Seven ε4 homozygotes out of a total of 538 DS adults have been reported in the literature. This number is not significantly different from that expected based on the ε4 allele frequencies in the individual series (p= 0.72). We conclude that there is little evidence that ε4/ε4 genotype frequency is substantially reduced in DS adults.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID