Tryptophan-5-hydroxylase activity in the rabbit brain synaptosomes at different times after the single administration of the opioid peptide Tyr-D-Ala-Gly-Phe-NH2

The activity of the key enzyme of serotonin biosynthesis--tryptophan-5-hydroxylase (T-5-H) was investigated in the synaptosomes of the motor cortex and caudate nucleus of the rabbit brain 30 min or 5 days after single injection of opioid tetrapeptidamide Tyr-D-Ala-Gly-Phe-NH2 (TPA). TPA was injected subcutaneously at a dose of 500 micrograms/kg of rabbit body weight. T-5-H activity in caudate nucleus synaptosomes was two times higher than that of the motor cortex synaptosomes and accounted for 159.67 and 80.84 pmoles of formed 5-hydroxytryptophan/mg protein per hour. 30 min after single injection of TPA the enzyme activity in the synaptosomes of the motor cortex and caudate nucleus decreased by 64.0 and 43.0%, respectively. 5 days following single TPA injection T-5-H activity in the motor cortex synaptosomes increased by 68.4% and in caudate nucleus synaptosomes decreased by 35.6%. Thus, it was established that TPA displayed a pronounced effect on T-5-H activity. The delayed effect of opioid TPA on T-5-H activity was discovered which was manifested on day 5 after the single injection. Possible mechanisms of TPA effect on T-5-H are discussed.     

电刺激大鼠尾核头部镇痛的中枢效应—[^3H]—2脱氧...

Sokoloff's 2-deoxyglucose (2-DG) autoradiographic technique was used to identify changes of glucose metabolic rate in the rat brain following unilateral stimulation of the head of the caudate nucleus. The results were as follows. The local glucose metabolic rate after noxious stimulation was increased in the somatosensory cortex, cingulate cortex, ventroposterior and parafascicular nucleus of the thalamus, septal area, habenular nucleus, head of caudate nucleus, periaqueductal gray (PAG) and dorsal raphe nucleus (P < 0.05). After stimulating the head of the caudate nucleus, the local glucose metabolic rate of nucleus raphe magnus (rm) and nucleus paragigantocellularis (pgcl) was increased significantly and that of the PAG and dorsal raphe nucleus had a tendency to increase, while stimulation of the head of caudate nucleus could partially abolish the increased glucose metabolic rate in the somatosensory cortex, cingulate cortex, ventroposterior and parafascicular nucleus of the thalamus, septal area and habenular nucleus as induced by noxious stimulation. These results suggest that caudate stimulation is able to depress the activation of some brain structures related to nociception and to activate those related to antinociception. The pgcl, rm, PAG and dorsal raphe nucleus might be the key structures participating in the caudate stimulation produced analgesia.     

THE EFFECTS OF PENTOBARBITONE-SODIUM ANAESTHESIA, SHOCK AVOIDANCE CONDITIONING AND ELECTRICAL SHOCK ON ACETYLCHOLINESTERASE ACTIVITY AND PROTEIN CONTENT IN REGIONS OF THE RAT BRAIN

Abstract— Pentobarbitone sodium anaesthesia was found to produce an increase in protein content in some regions of the rat brain, i.e. posterior cortex, caudate nucleus, and a decrease in protein content in the ventral cortex.
Acetylcholinesterase expressed in terms of wet weight was found to increase in the cerebellum, medulla, and to decrease in the medial cortex, hippocampus, thalamus and caudate nucleus. The changes in activity were not explicable in terms of a direct effect of the anaesthetic on the enzyme. A decrease in protein content of rat brain was observed in the frontal cortex, ventral cortex, hippocampus and caudate nucleus after electrical shocks. Following shock avoidance conditioning procedure (shuttle-box), decreases in protein content were observed in the medial cortex, posterior cortex, cerebellum and ventral cortex; in the thalamus an increase in protein content was observed.
Changes in AChE activity were observed following footshock in the frontal cortex and medulla where there was an increase in activity and in the caudate nucleus, hypothalamus, thalamus, and olfactory tubercle where there was a decrease in activity.
Following shock avoidance conditioning the activity of the AChE increased in posterior cortex, hippocampus, thalamus and hypothalamus and the activity of the enzyme decreased in the ventral cortex.     

电刺激大鼠尾核头部镇痛的中枢效应——〔~3H〕-2脱氧葡萄糖放射自显影研究

本文利用[~3H]-2脱氧葡萄糖定量放射自显影方法,研究了电刺激大鼠尾核头部镇痛时中枢神经系统有关结构的葡萄糖代谢率变化。结果表明,痛刺激后,皮层躯体感觉Ⅰ,Ⅱ区、扣带回皮质、丘脑束旁核、丘脑中央中核、丘脑腹后核、尾核、外侧缰核、外侧隔核、中缝背核及中脑导水管周围灰质等结等的葡萄糖代谢率均明显升高(P<0.05)。电刺激大鼠尾核头部后,中缝大核及延髓旁巨细胞网状外侧核的葡萄糖代谢率显著升高,中脑导水管周围灰质和中缝背核的葡萄糖代谢率亦有升高趋势。电刺激大鼠尾核头部可部份降低痛刺激引起的有关结构葡萄糖代谢率升高(如皮层躯体感觉Ⅰ、Ⅱ区、扣带回皮质、丘脑束旁核、丘脑中央中核、丘脑腹后核、外侧隔核及外侧缰核等)。上述结果提示,电刺激大鼠尾核头部镇痛时抑制了与痛感觉有关的结构,同时激活了与镇痛有关的结构。中缝大核、中缝背核、中脑导水管周围灰质及延髓旁巨细胞网状外侧核等结构是实现尾核镇痛的重要环节。     

Effect of chlorpromazine on central nervous system concentrations of manganese,iron, and copper

Chronic administration of chlorpromazine produced alterations in trace metal concentrations in caudate nucleus, frontal cortex, and cerebellar hemisphere of guinea pigs. Manganese concentration following chronic chlorpromazine rose significantly in the caudate nucleus and cerebellar hemisphere whereas iron concentration rose most significantly in the caudate nucleus. Copper content was decreased in all regions examined. The possible significance of increased manganese and iron in the caudate nucleus is discussed in relationship to the clinical problems of chlorpromazine-induced dyskinesias.     

Neurotransmitter receptor alterations in Parkinson's disease.

Neurotransmitter receptor binding for GABA, serotonin, cholinergic muscarinic and dopamine receptors and choline acetyltransferase (ChAc) activity were measured in the frontal cortex, caudate nucleus, putamen and globus pallidus from postmortem brains of 10 Parkinsonian patients and 10 controls. No changes in any of these systems were observed in the frontal cortex. In the caudaye nucleus, only the apparent dopamine receptor binding was altered with a significant 30% decrease in the Parkinsonian brain. Both cholinergic muscarinic and serotonin receptor binding were significantly altered in the putamen, the former increasing and the latter decreasing with respect to controls. In addition, ChAc activity was decreased in the putamen. In the globus pallidus, only ChAc activity was significantly changed, decreasing about 60%, with no change in neurotransmitter receptor binding. The results suggest that a progressive loss of dopaminergic receptors in the caudate nucleus may contribute to the decreased response of Parkinsonian patients to L-dopa and dopamine agonist therapy.     

Reduced Neuropeptide Y Concentrations in Suicide Brain

Neuropeptide Y (NPY) was measured in postmortem brain tissue from victims of suicide and from individuals dying a sudden natural or accidental death (controls). Concentrations of NPY-immunoreactivity were measured by radioimmunoassay in frontal cortex (BA 10), temporal cortex (BA 22), caudate nucleus, and cerebellum. Concentrations of NPY-immunoreactivity were significantly lower in postmortem frontal cortex (-14%) and caudate nucleus (-27%) from suicide victims compared with age-matched controls. A subgroup of suicides with evidence of a history of depression revealed more robust reductions in concentrations of NPY-immunoreactivity in frontal cortex and caudate nucleus, as did four individuals who died from natural causes and also were described as having a possible history of depression. Concentrations of NPY-immunoreactivity in temporal cortex and cerebellum from victims of suicide or from the subgroup of subjects with a possible history of depression were not significantly different from those of age-matched controls. We suggest there is a deficit in the brain NPY system leading to region-specific reductions in peptide concentrations in subjects who have a history of depression.     

Region-Selective Decreases in Densities of [3H]Tryptamine Binding Sites in Autopsied Brain Tissue from Cirrhotic Patients with Hepatic Encephalopathy

Abstract: The distribution of [³H]tryptamine binding sites, in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy (HE) and an equal number of age-matched control subjects free from hepatic, neurological, or psychiatric disorder, was investigated. Scatchard analysis demonstrated a heterogeneous distribution for this binding site, with the highest density being observed in hippocampus ≫ frontal cortex = caudate nucleus > temporal cortex = cerebellum. When comparing [³H]-tryptamine binding site densities in control brain tissue with that in brain tissue from patients with HE, significant decreases in densities were observed in the frontal cortex (by 56%, p < 0.001), hippocampus (by 43%, p < 0.001), and caudate nucleus (by 41%, p < 0.01) of the HE group. Binding site affinities were within normal limits. The findings of decreased densities of [³H]tryptamine binding sites taken in conjunction with previous reports of increased CSF and brain tryptamine concentrations in HE suggest a pathogenic role for this neuroactive amine in HE resulting from chronic liver failure.     

Effect of electrical stimulation of the caudate nucleus on the functionally identified neurons of the sensory-motor cortex in the cat brain

Specifics of the caudate nucleus effect upon specific and unspecific responses of the cat brain sensory-motor cortex involves an individual inhibition and temporal modulation of unspecific activity of the cortical neurons, whereas specific responses of the same cells remain the same.     

GABA receptor binding in the parkinsonian brain

The binding of GABA to postsynaptic receptors was studied in the cerebral and cerebellar cortex, caudate nucleus, putamen, pallidum and substantia nigra from autopsy brains of 12 parkinsonian patients and 11 controls. GABA receptor binding in the substantia nigra was significantly decreased in the parkinsonian brain. In the other brain regions, however, GABA binding was unchanged. There was no correlation between GABA binding and sex, age, duration or severity of the disease. The results suggest the involvement of nigral GABA receptor in Parkinson's disease.     

Conditioned reflexes following unilateral damage to the premotor cortex and the dorsal portion of the head of the caudate nucleus in dogs

The study was carried out on dogs by the secretory-motor method with a two-side reinforcement. Simultaneous and unilateral lesion of the premotor cortex and of the dorsal part of the caudate nucleus head brought about prolonged disturbances of the vegetative components (pulse and respiratory rate) and in the choice of the side of food reinforcement. The change in the magnitude of conditioned salivation, latencies of secretion and motor reaction was temporary, and by the end of the third postoperative period their initial magnitudes were restored. The duration of the disturbances of higher nervous activity depended on the localization and extent of lesion of the caudate nucleus head. Tests were made with chlorpromazine and caffeine before and after the lesion of the brain structures. The tests in the postoperative period revealed latent disturbances in the dog higher nervous activity. It is assumed that the premotor cortex and the dorsal part of the caudate nucleus head are one of the sub-systems involved in the regulation of vegetative, somatic components of unconditioned behaviour and in the analysis of conditioned stimuli.     

Effect of aminazin and haloperidol on the content of glial fibrillar acid protein in the rat brain]

The immune-enzyme analysis was used to determine the quantity of glial fibrillar acid protein in the water-soluble extracts of frontal and limbic cortex, caudate nucleus, medulla oblongata of rats before and after administration of aminazin and haloperidol. The obtained results testify to a decrease of the protein content under the action of both neuroleptics only in the limbic brain cortex of rats.     

Change in the functional significance of structures of the cat brain as a result of reorganization of its activity

A study was carried out on 8 adult cats of functional role of the frontal, parietal and occipital parts of the neocortex, and also of the dorsal hippocampus, mediodorsal thalamic nucleus and caudate nucleus head, in realization of a delayed spatial choice (DSCh) before and after compensatory reorganizations of the brain activity caused by multiple electrical stimulation of the frontal part of the cerebral cortex. Compensatory reorganization led to a change of functional significance of these structures. While before this change the frontal cortex, hippocampus and mediodorsal thalamic nucleus were critically necessary brain areas for the realization of the DSCh, after it parietal and occipital cortical areas acquired such significance. The obtained data are discussed proceeding from the principle of the integrity in the brain activity.     

Cerebrovascular reserve in the cat after acute bilateral carotid occlusion

Cerebral blood flow in the cat was studied before and after acute bilateral common carotid occlusion under normocapnic and hypercapnic conditions and after induced hypotension. Regional blood flow to different brain structures was studied with the microsphere method. Local blood flow in the caudate nucleus, the cerebral cortex and medulla oblongata was studied with H2-polarography. Although the blood flow to the anterior brain regions is significantly decreased after bilateral common carotid occlusion, their blood supply is kept above ischaemic levels by re-distribution of the vertebrobasilar flow. Cerebrovascular reserve in anterior brain regions, however, is lost as indicated by the severe impairment of both the flow response to hypercapnia and to blood pressure decrease. After bilateral common carotid occlusion paradoxical CO2-reactions, indicating intracerebral steal, were seen in the caudate nucleus. In posterior brain regions resting blood flow, flow-reaction to hypercapnia and to hypotension are better preserved under these conditions. Measurement of the CBF responses to induced hypercapnia is a dependable test for appreciation of cerebrovascular reserve after cerebrovascular occlusion but may be potentially hazardous where local flow is close to ischaemic levels.     

CNS depressive role of aqueous extract of Spinacia oleracea L. leaves in adult male albino rats

Treatment with Spinacia oleracea extract (SO; 400 mg/kg body weight) decreased the locomotor activity, grip strength, increased pentobarbitone induced sleeping time and also markedly altered pentylenetetrazole induced seizure status in Holtzman strain adult male albino rats. SO increased serotonin level and decreased both norepinephrine and dopamine levels in cerebral cortex, cerebellum, caudate nucleus, midbrain and pons and medulla. Result suggests that SO exerts its CNS depressive effect in PTZ induced seizure by modulating the monoamines in different brain areas.     

The mechanism of electrically stimulated adenosine release varies by brain region

Adenosine plays an important role in neuromodulation and neuroprotection. Recent identification of transient changes in adenosine concentration suggests adenosine may have a rapid modulatory role; however, the extent of these changes throughout the brain is not well understood. In this report, transient changes in adenosine evoked by one second, 60 Hz electrical stimulation trains were compared in the caudate–putamen, nucleus accumbens, hippocampus, and cortex. The concentration of evoked adenosine varies between brain regions, but there is less variation in the duration of signaling. The highest concentration of adenosine was evoked in the dorsal caudate–putamen (0.34?±?0.08 μM), while the lowest concentration was in the secondary motor cortex (0.06?±?0.02 μM). In all brain regions, adenosine release was activity-dependent. In the nucleus accumbens, hippocampus, and prefrontal cortex, this release was partly due to extracellular ATP breakdown. However, in the caudate–putamen, release was not due to ATP metabolism but was ionotropic glutamate receptor-dependent. The results demonstrate that transient, activity-dependent adenosine can be evoked in many brain regions but that the mechanism of formation and release varies by region.     

Neurophysiological analysis of postnatal development of corticostriate connections in rabbits

Evoked potentials were recorded in the caudate nucleus of adult rabbits and young rabbits aged 2–30 days in response to stimulation of the ipsilateral motor cortex. The response of the caudate nucleus in the adult rabbit consisted of a positive-negative complex with latent period of 3–5 msec. Maximal amplitude of the response was observed in the dorsorostral region of the nucleus. As the recording electrode was inserted deeper, the amplitude of the response gradually decreased but without reversal of its polarity. Responses of the caudate nucleus to stimulation of the motor cortex were recorded as early as on the 3rd day after birth. These responses were indistinguishable in configuration from responses of the nucleus of adult rabbits. Their latent period was about 10 msec. Between the 16th and 20th day after birth the latent period of the response decreased considerably — from 9 to 5 msec, and by the 30th day of life it had reached its definitive value. With age the amplitude of the response increased but the threshold of stimulation decreased, The results indicate early functional maturation of connections of the motor cortex with the caudate nucleus and they agree with the results of morphological investigations of the structural development of the afferent systems of this nucleus.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 14, No. 3, pp. 284–289, May–June, 1982.     

Connections of various fields of the parietal cortex with the caudate nucleus of the cat brain

By means of the light and electron microscopy methods efferent connections of the fields 5a, 5b and 7 with the caudate nucleus have been studied. These fields are predominantly projected to the dorsolateral corner of the middle and posterior head of the caudate nucleus. The fields 5b and 7, unlike the field 5a, give also origin to the fibers, terminating in the central part of the head and in the caudate nucleus body. The electron microscopic investigation proves the monosynaptic nature of the fields 5a, 5b and 7 with the dorsolateral part of the middle and posterior parts of the caudate nucleus head. The parietal cortex gives origin, mainly, to fine myelin fibers (0.665 +/- 0.029), terminating in the part mentioned of the caudate nucleus. These fibers form small terminals (0.310 +/- 0.014 to 0.430 +/- 0.020 mcm) with asymmetrical membranous thickening; these terminals end on the spines (with a poorly expressed spine apparatus) of the dendrites, evidently, of the middle spine cells. Axonal terminals of the parietal cortex form axodendritic terminals extremely seldom. Axospinous synapses on the dendrites of the middle spine cells, situating in the dorsolateral part of the caudate nucleus head are supposed to be a morphological substrate, ensuring the cortical control of the parietal cortex at the level of the caudate nucleus.     

EFFECT OF DIAZEPAM AND PENTOBARBITAL ON AMINOOXYACETIC ACID-INDUCED ACCUMULATION OF GABA

Abstract— The effect of diazepam and pentobarbital on γ-aminobutyric acid (GABA) levels, the aminooxyacetic acid (AOAA)-induced accumulation of GABA, and the in vitro activity of l -glutamate 1-carboxyl-lyase (EC 4.1.1.15) [GAD] were studied in various regions of rat brain. Diazepam increased GABA levels in the substantia nigra, diminished the AOAA-induced accumulation of GABA in the caudate nucleus, cingulate, parietal and entorhinal cortex and had no effect on GABA accumulation in the pyriform and cerebellar cortex. After pentobarbital, GABA levels were elevated in the caudate nucleus but decreased in the parietal and pyriform cortex; the AOAA-induced accumulation of GABA also diminished in all cortical regions studied. No correlation was found between the apparent changes in GABA synthesis, as estimated by accumulation after inhibition of 4-aminobutyrate-2-oxoglu-tarate (EC 2.6.1.19) [GABA-T] with AOAA, and the changes in GABA levels induced by these drugs. The reduction in AOAA-induced GABA accumulation after diazepam and pentobarbital treatment was most pronounced in regions which showed the greatest accumulation of GABA after AOAA administration. Neither diazepam nor pentobarbital administration affected the activity of GAD in homogenates of cingulate cortex. Chlorpromazine, at a dose which decreased spontaneous activity, enhanced the AOAA-induced GABA accumulation in the cingulate cortex, suggesting that drug-induced sedation is not necessarily associated with decreased GABA synthesis. While regional differences were observed in the effects of diazepam and pentobarbital on GABA synthesis, both agents appear to inhibit GABA synthesis in vivo and both do so, in at least some brain areas, at subsedative doses.     

Effect of swinging on EEG of rats of juvenile age in the wakefulness state

Simultaneous recording of the EEG activity of superficial cortical and deep (caudate nucleus, dorsal hippocampus, anterior hypothalamus) brain parts has been performed for the first time after a 2-h swinging of frequency of 0.2 Hz in Wistar rats of juvenile age. Swinging was produced on a 4-bar parallel swing. Using a Neuron-Spectr electroencephalograph and a Diana program, normalized power spectra of wave EEG components, synchronization coefficients, and coefficients of cross-correlation between bioelectrical potentials of various brain structures were determined. After a 2-h swinging, the mean value of normalized power of slow waves of delta-diapason in hypothalamus and hippocampus was found to increase statistically significantly, while normalized power of fast waves of alpha- and beta1-diapasons in hippocampus decreased (p < 0.05). A statistically significant increase of synchronization coefficient was observed in hypothalamus and hippocampus. Changes of coefficients of cross-correlation between hypothalamus and hippocampus and other brain strictures were of the oppositely directed, individual character. In the parietal occipital brain cortex and in caudate nucleus, the changes of the EEG spectral composition also were of individual character. The obtained results on the whole correspond to data about an enhancement of the EEG low-frequency rhythms at swinging and agree with the resonance hypothesis of motion sickness.