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 共查询到20条相似文献,搜索用时 31 毫秒
1.
J G Salamy  S F Sands  N Dafny 《Life sciences》1979,24(14):1241-1249
The effects of morphine on averaged evoked responses to visual stimulation were examined in specific brain structures relevant to pain, analgesia, tolerance and motor disturbances. Permanent electrodes (60 μ in diameter) were implanted stereotaxically in the central gray, mesencephalic reticular formation, caudate nucleus, parafasicular-centromedian complex and the lateral geniculate body as a control site. Visual evoked responses were obtained in unanesthetized, unrestrained rats prior to and following the administration of morphine in successive doses of 1, 5, 10 and 30 mg/kg and 1 mg/kg of naloxone (a morphine antagonist). The parafasicular-centromedian complex and the reticular formation exibited a progressive increase in response amplitude to increased dose of morphine. These effects were reversed by naloxone. In this study the parafasicular-centromedian complex was found to be the most sensitive structure to morphine, displaying the largest changes in response amplitude as a result of morphine administration.  相似文献   

2.
万涛  郑军 《生命的化学》2021,(2):361-367
纳布啡是一种新型的菲族镇痛药,属于混合型阿片类受体激动/拮抗剂,可在脊髓水平激动κ受体发挥强效的镇痛效果,其镇痛作用起效迅速、药效持久、疗效确切;同时由于纳布啡独特的部分μ受体拮抗特性,使其与吗啡相比,在发挥镇痛作用的同时呼吸抑制轻、血流动力学平稳以及恶心呕吐、皮肤瘙痒、成瘾性等不良反应发生率更低,因此,纳布啡在围手术期镇痛和临床麻醉等多个领域有着广阔的应用前景。现结合纳布啡独特的药代动力学、药理学特点及作用机制,对纳布啡在围手术期镇痛的研究进展作一综述,以期为临床上合理、有效镇痛提供理论参考和实践依据。  相似文献   

3.
Neuroimaging studies of obsessive-compulsive disorder have found abnormalities in orbitofronto-striato-thalamic circuitry, including the orbitofrontal cortex, anterior cingulate cortex, caudate, and thalamus, but few studies have explored abnormal intrinsic or spontaneous brain activity in the resting state. We investigated both intra- and inter-regional synchronized activity in twenty patients with obsessive-compulsive disorder and 20 healthy controls using resting-state functional magnetic resonance imaging. Regional homogeneity (ReHo) and functional connectivity methods were used to analyze the intra- and inter-regional synchronized activity, respectively. Compared with healthy controls, patients with obsessive-compulsive disorder showed significantly increased ReHo in the orbitofrontal cortex, cerebellum, and insula, and decreased ReHo in the ventral anterior cingulate cortex, caudate, and inferior occipital cortex. Based on ReHo results, we determined functional connectivity differences between the orbitofrontal cortex and other brain regions in both patients with obsessive-compulsive disorder and controls. We found abnormal functional connectivity between the orbitofrontal cortex and ventral anterior cingulate cortex in patients with obsessive-compulsive disorder compared with healthy controls. Moreover, ReHo in the orbitofrontal cortex was correlated with the duration of obsessive-compulsive disorder. These findings suggest that increased intra- and inter-regional synchronized activity in the orbitofrontal cortex may have a key role in the pathology of obsessive-compulsive disorder. In addition to orbitofronto-striato-thalamic circuitry, brain regions such as the insula and cerebellum may also be involved in the pathophysiology of obsessive-compulsive disorder.  相似文献   

4.
Mice were rendered dependent on morphine by mixing morphine with their food (2 mg/g) for three days. Increasing doses of naloxone precipitated dose-dependent withdrawal reactions such as weight loss and jumping. These withdrawal reactions were antagonized by morphine pretreatment. Effects of morphine, such as increased locomotor activity, inhibition of intestinal transport, and analgesia were antagonized by naloxone in both non-dependent and dependent subjects. The antagonist actions of naloxone were increased in dependent subjects; lower doses of naloxone were sufficient to antagonize effects of morphine. The present results confirm earlier studies indicating that precipitation of withdrawal can be antagonized by morphine pretreatment suggesting that withdrawal reactions are due to actions of naloxone at the same receptor at which opioid agonists act. The increased antagonist potency of naloxone in dependent subjects extends earlier results obtained with analgesic effects to several other agonist effects of morphine and is consistent with the interpretation that exposure to an opioid agonist induces a change in the conformation of opioid receptors.  相似文献   

5.
R Tashev  S Belcheva  K Milenov  I Belcheva 《Peptides》2001,22(7):1079-1083
The effects of somatostatin microinjected bilaterally and unilaterally (left or right) at a dose of 10, 50 and 100 ng into the caudate putamen of male Wistar rats on nociception (analgesy-meter test) were studied. Somatostatin injected into caudate putamen resulted in analgesia. Bilateral microinjections of somatostatin significantly increased the pain threshold in a dose-dependent manner, i.e. somatostatin exerted antinociceptive effect. The pain threshold after left-side microinjections was significantly higher than that after injections into right-side. These findings suggest antinociceptive and asymmetric effects of somatostatin on pain in the caudate putamen.  相似文献   

6.
Vasopressin analgesia: specificity of action and non-opioid effects   总被引:3,自引:1,他引:3  
J H Kordower  R J Bodnar 《Peptides》1984,5(4):747-756
Recent neuroanatomical and behavioral evidence has indicated that vasopressin (VP) increases pain thresholds. In the present study intracerebroventricular (ICV) administration of both arginine VP (AVP: 75-500 ng) and 1-deamino-8-D-arginine vasopressin (DDAVP: 150-500 ng) elevated tail flick latencies. Oxytocin (OXY, ICV), also elevated tail-flick latencies (150-1000 ng); however this increase was accompanied by "barrel-roll" seizure activity. VP analgesia was eliminated by pretreatment with 1-deamino-penicillamine-2(O-methyl)tyrosine-AVP (dPTyr(me)AVP: 500 ng, ICV), a VP antagonist, but not naloxone (1 or 10 micrograms, ICV), suggesting that VP modulates nonciceptive thresholds through its own binding sites. Conversely, pretreatment with naloxone (1 micrograms, ICV) but not dPTyr(me)AVP (1 microgram, ICV) attenuated the analgesic efficacy of systemic morphine (10 mg/kg), further dissociating VP and central opiate analgesic processes. Finally, systemic pretreatment with dexamethasone potentiated VP analgesia. These data support the notion that VP is a specific non-opioid pain inhibitor.  相似文献   

7.
Adult male ICR mice were treated by intraperitoneal injection with 250?mg/kg of bodyweight of commercial malathion (a dose corresponding to 1/12 the LD50). After 6?h, acetylcholinesterase (AChE) activity in blood, liver, and six brain regions was determined. A statistically significant inhibition was observed in whole blood (23%), liver (21%), and, in particular, the central nervous system; the greatest degree of AChE inhibition was observed in the cerebellum (45%), followed by the hippocampus (29%). There was no significant change in AChE activity in the caudate putamen, frontal cortex, midbrain, or pons medulla. These results demonstrate that the magnitude of AChE inhibition in peripheral tissues does not accurately reflect the central-inhibitory effects of malathion on AChE activity in specific brain regions.  相似文献   

8.
Adult male ICR mice were treated by intraperitoneal injection with 250 mg/kg of bodyweight of commercial malathion (a dose corresponding to 1/12 the LD50). After 6 h, acetylcholinesterase (AChE) activity in blood, liver, and six brain regions was determined. A statistically significant inhibition was observed in whole blood (23%), liver (21%), and, in particular, the central nervous system; the greatest degree of AChE inhibition was observed in the cerebellum (45%), followed by the hippocampus (29%). There was no significant change in AChE activity in the caudate putamen, frontal cortex, midbrain, or pons medulla. These results demonstrate that the magnitude of AChE inhibition in peripheral tissues does not accurately reflect the central-inhibitory effects of malathion on AChE activity in specific brain regions.  相似文献   

9.
Huntington's Disease, an autosomal dominant neurological disorder, is characterized by diffuse neuronal degeneration particularly in the basal ganglia and cerebral cortex. The purpose of this study was to examine various discrete regions of choreic and control brains for alterations in muscarinic cholinergic receptor binding and choline acetyltransferase (ChAc) activity. Nine postmortem brains, three from patients with Huntington's Disease and six controls, were dissected into 17 discrete regions. Each regional homogenate was assayed for muscarinic receptor concentration by measuring specific membrane binding of [3H]-QNB, a potent muscarinic antagonist which selectively labels brain muscarinic receptors. Aliquots from each brain region were also assayed for ChAc activity. Of significance was the marked reduction in specific [3H]-QNB receptor binding in the caudate nucleus, putamen and globus pallidus of choreic brain while no significant alterations were detected in other brain regions. Significant decreases in ChAc activity were found in the caudate nucleus, putamen, and globus pallidus with no alterations in ChAc activity in the rest of the brain regions examined. The tissues were chosen such that protein levels were similar in both choreic and normal brain samples. The apparent reduction in the number of muscarinic cholinergic receptors in the choreic brains suggests that treatment with cholinomimetic drugs might be beneficial in Huntington's Disease.  相似文献   

10.
Affective instability and self-injurious behavior are important features of Borderline Personality Disorder. Whereas affective instability may be caused by a pattern of limbic hyperreactivity paired with dysfunctional prefrontal regulation mechanisms, painful stimulation was found to reduce affective arousal at the neural level, possibly underlying the soothing effect of pain in BPD.We used psychophysiological interactions to analyze functional connectivity of (para-) limbic brain structures (i.e. amygdala, insula, anterior cingulate cortex) in Borderline Personality Disorder in response to painful stimulation. Therefore, we re-analyzed a dataset from 20 patients with Borderline Personality Disorder and 23 healthy controls who took part in an fMRI-task inducing negative (versus neutral) affect and subsequently applying heat pain (versus warmth perception).Results suggest an enhanced negative coupling between limbic as well as paralimbic regions and prefrontal regions, specifically with the medial and dorsolateral prefrontal cortex, when patients experienced pain in addition to emotional arousing pictures. When neutral pictures were combined with painful heat sensation, we found positive connectivity in Borderline Personality Disorder between (para-)limbic brain areas and parts of the basal ganglia (lentiform nucleus, putamen), as well areas involved in self-referential processing (precuneus and posterior cingulate).We found further evidence for alterations in the emotion regulation process in Borderline Personality Disorder, in the way that pain improves the inhibition of limbic activity by prefrontal areas. This study provides new insights in pain processing in BPD, including enhanced coupling of limbic structures and basal ganglia.  相似文献   

11.
The temporoparietal junction (TPJ) is a key node in the brain's ventral attention network (VAN) that is involved in spatial awareness and detection of salient sensory stimuli, including pain. The anatomical basis of this network's right-lateralized organization is poorly understood. Here we used diffusion-weighted MRI and probabilistic tractography to compare the strength of white matter connections emanating from the right versus left TPJ to target regions in both hemispheres. Symmetry of structural connectivity was evaluated for connections between TPJ and target regions that are key cortical nodes in the right VAN (insula and inferior frontal gyrus) as well as target regions that are involved in salience and/or pain (putamen, cingulate cortex, thalamus). We found a rightward asymmetry in connectivity strength between the TPJ and insula in healthy human subjects who were scanned with two different sets of diffusion-weighted MRI acquisition parameters. This rightward asymmetry in TPJ-insula connectivity was stronger in females than in males. There was also a leftward asymmetry in connectivity strength between the TPJ and inferior frontal gyrus, consistent with previously described lateralization of language pathways. The rightward lateralization of the pathway between the TPJ and insula supports previous findings on the roles of these regions in stimulus-driven attention, sensory awareness, interoception and pain. The findings also have implications for our understanding of acute and chronic pains and stroke-induced spatial hemineglect.  相似文献   

12.
Regulation of heme and drug metabolism activities in the brain by manganese   总被引:2,自引:0,他引:2  
A novel effect of metal ions in the brain is described. Mn was found to alter heme metabolism and the cytochrome P-450-dependent mixed-function oxidase activities in rat brain. A more than 2-fold increase in benzo(alpha)pyrene hydroxylase and 7-ethoxycoumarin deethylase activities were observed in the brain of rats treated for 7 days with Mn. The increases were regionally distributed; the highest elevations were observed in the hippocampus, pons and the caudate putamen. Moreover, in rats treated with Mn for 1 or 7 days a marked depression in the activity of the mitochondrial ALA synthetase was observed. The activity of the microsomal heme oxygenase was also inhibited at 7 days, but not 1 day, after Mn treatment. These inhibitions were reflected in an initial decrease, followed by a rebound return to normal, in the concentration of cytochrome P-450 in the brain. Mn was ineffective in vitro in altering heme and drug metabolism activities. It is suggested that Mn-mediated alterations in heme metabolic activities promote changes in the composition of cytochrome P-450 species in the brain microsomal fractions, such that the relative concentrations of the molecular species which catalyse aryl hydrocarbon hydroxylase activity become selectively increased.  相似文献   

13.
1. The present study compares the direct actions of morphine on two brain sites known to be rich in opiate receptors, namely, the caudate nucleus and the central gray. Recordings and morphine injections were made through a multibarrel glass micropipette using microiontophoresis. 2. Four different patterns of neuronal response to increasing currents of morphine were recorded in both brain regions. 3. Differences in the response to morphine between the two sites were detected in morphine-dependent rats. While the caudate neurons exhibited super-sensitivity to morphine, the neurons in the central gray displayed tolerance, and in some instances, dependence was evident when naloxone was administered. 4. The distribution of spontaneously active neurons within these two brain areas was found to be different in morphine-naive and morphine-dependent rats. 5. The electrophysiological findings of this study support the hypothesis of multiple opiate receptors.  相似文献   

14.
Z Wang  Z Zhang  Q Jiao  W Liao  G Chen  K Sun  L Shen  M Wang  K Li  Y Liu  G Lu 《PloS one》2012,7(7):e39701

Objective

Neuroimaging evidence suggested that the thalamic nuclei may play different roles in the progress of idiopathic generalized epilepsy (IGE). This study aimed to demonstrate the alterations in morphometry and functional connectivity in the thalamic nuclei in IGE.

Methods

Fifty-two patients with IGE characterized by generalized tonic-clonic seizures and 67 healthy controls were involved in the study. The three-dimensional high-resolution T1-weighted MRI data were acquired for voxel-based morphometry (VBM) analysis, and resting-state blood-oxygenation level functional MRI data were acquired for functional connectivity analysis. The thalamic nuclei of bilateral medial dorsal nucleus (MDN) and pulvinar, as detected with decreased gray matter volumes in patients with IGE through VBM analysis, were selected as seed regions for functional connectivity analysis.

Results

Different alteration patterns were found in functional connectivity of the thalamic nuclei with decreased gray matter volumes in IGE. Seeding at the MDN, decreased connectivity in the bilateral orbital frontal cortex, caudate nucleus, putamen and amygdala were found in the patients (P<0.05 with correction). However, seeding at the pulvinar, no significant alteration of functional connectivity was found in the patients (P<0.05 with correction).

Conclusions

Some specific impairment of thalamic nuclei in IGE was identified using morphological and functional connectivity MRI approaches. These findings may strongly support the different involvement of the thalamocortical networks in IGE.  相似文献   

15.
The stimulation of dopaminergic receptors, inhibition of serotonin synthesis or blockade of muscurinic receptors by various modifiers led to inhibition of morphine analgesia in mice. Blockade of dopaminergic receptors or the increase in serotonergic or cholinergic activity resulted in the enhancement of morphine analgesia. Serotonergic and cholinergic systems are proposed as positive and the dopaminergic system as negative modulators of morphine analgesia. The modulation of naloxone antagonism was much more complicated than that of morphine analgesia and often the effect of biogenic amine-modifiers on antagonism differed from that on analgesia. The fact that biogenic amine-modifiers do not affect morphine analgesia and naloxone antagonism by a similar pattern suggest that interaction of narcotics and narcotic antagonists with analgesic receptors may not be exactly the same.  相似文献   

16.
The effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on pain sensitivity, on morphine analgesia, on morphine tolerance and withdrawal were investigated in mice. The heat-radiant tail-flick test was used to assess antinociceptive threshold. Intracerebroventricular (i.c.v.) administration of PACAP alone had no effect on pain sensitivity but in a dose of 500 ng, it significantly diminished the analgesic effect of a single dose of morphine (2.25 mg/kg, s.c.). PACAP (500 ng, i.c.v.) significantly increased the chronic tolerance to morphine and enhanced the naloxone (1 mg/kg, s.c.)-precipitated withdrawal jumping. Theophylline (1 mg/kg, i.p.) pretreatment significantly enhanced the effect of PACAP on morphine analgesia but the effects of PACAP on tolerance and withdrawal were unaffected upon theophylline administration. On the grounds of our previous studies with vasoactive intestinal polypeptide (VIP), it appears that different receptors are involved in the effects of PACAP in acute and chronic morphine actions. Our results indicate that PACAP-induced actions likely participate in acute and chronic effects of morphine and suggest a potential role of PACAP in opioid analgesia, tolerance and withdrawal.  相似文献   

17.
[3H] 1-Nicotine was used as a receptor ligand in the intact mouse. It was injected i.v., and radioactivity in brain regions was assayed. Nonspecific binding was estimated by pretreatment with unlabelled 1-nicotine. Radioactivity entered the brain rapidly, was heterogeneously distributed, and declined after 5 min. Estimated specific binding was highest in the medial and posterior cortex, midbrain, thalamus/hypothalamus and medulla/pons; intermediate in the cerebellum, caudate/putamen, frontal and frontoparietal cortex; and lowest in the hippocampus and olfactory bulb. Autoradiography showed similar patterns. Coinjection of unlabelled 1-nicotine reduced specific binding so that it approached estimated nonspecific binding. Nicotinic agonists reduced radioactivity in the thalamus/hypothalamus, but nicotinic antagonists were less active. Non-nicotinic drugs did not reduce brain radioactivity. The results suggest that radiolabelled nicotine may be used for in vivo receptor studies despite problems in estimating nonspecific binding.  相似文献   

18.
19.
Methionine- and leucine-enkephalin were found to be potent, short-acting analgesics in the tail flick test in rats following intracerebral administration, via chronically indwelling cannulae, into the midbrain periaqueductal gray. Morphine sulfate was approximately 4 times as potent as the enkephalins when infused into this same brain site. The analgesia produced by the enkephalins and by morphine was inhibited by pretreatment with naloxone.  相似文献   

20.
The enzyme 8-oxoguanine DNA glycosylase 1 participates in the repair of damaged DNA by excising the oxidized base 8-hydroxy-2'-deoxyguanosine. We have previously demonstrated that enzymatic activity of this enzyme is inversely related to the levels of the damaged base in specific brain regions. We now report that the activity of 8-oxoguanine DNA glycosylase 1 is increased in a region-specific manner following treatment with diethylmaleate, a compound that reduces glutathione levels in the cell. A single treatment with diethylmaleate elicited a significant increase ( approximately 2-fold) in the activity of 8-oxoguanine DNA glycosylase 1 in three brain regions with low basal levels of activity (cerebellum, cortex, and pons/medulla). There was no change in the activity of 8-oxoguanine DNA glycosylase 1 in those regions with high basal levels of activity (hippocampus, caudate/putamen, and midbrain). This is the first report to demonstrate that DNA repair capacity can be upregulated in the CNS, and the increased repair activity correlates with a reduction in the levels of DNA damage. The brain region-specific capacity to deal with increased oxidative damage to DNA may be responsible, in part, for the vulnerability of specific neuronal populations with aging, sources of oxidative stress, and neurodegenerative diseases.  相似文献   

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