Behavioural and electrocortical effects after injection of two ornithine decarboxylase inhibitors into several areas of the brain in the rat

The behavioural and electrocortical effects of alpha-methylornithine and alpha-difluoromethylornithine, two ornithine decarboxylase inhibitors, were evaluated after their infusion into several areas of the brain in the rat. Both compounds induced, in dose-dependent manner, similar epileptogenic effects, stereotyped behaviour and postural asymmetry, depending upon the site of injection. Unilateral injection of DFMO into the entopeduncular nucleus or the substantia nigra pars reticulata, caused an increase in locomotor activity. Unilateral injection of DFMO into the caudate nucleus or the substantia nigra pars compacta had no effect on locomotor activity. Among the areas of the brain studied, the most sensitive site from which electrocortical epileptogenic disorders were evoked, was the hippocampus. The GABA agonist muscimol, infused prior to DFMO, resulted in an anticonvulsant action, while DFMO, infused prior to putrescine, increased the convulsant properties of putrescine. In conclusion, these results indicate that DFMO and alpha-methylornithine produced epileptogenic effects after their intracerebral infusion and suggest that may act as analogues of putrescine.     

Behavioural and electrocortical modifications induced in the rat by intraventricular injection of physalaemin and eledoisin

The effects of intraventricular injection of eledoisin and physalaemin in the rat were studied. Both peptides reduced explorative behaviour; eledoisin, but not physalaemin, produced catatonia, reduction of muscular strength, tremor and sialorrhea. The electrocorticogram showed the signs of a depressive effect both after physalaemin and eledoisin administration.     

Quantitative electrocortical changes in the rat induced by phencyclidine and other stimulants

An automated technique for the continuous analysis of different frequency bands of the electrocorticogram (ECoG) of the rat has been used to quantify the actions of phencyclidine (PCP) and various other stimulant drugs. It has been demonstrated that phencyclidine, etoxadrol and LY154045 produced similar changes in the individual frequency bands whereas amphetamine and apomorphine had different profiles of activity. The phencyclidine-like compounds exhibited extremely strong stimulation of the ECoG with very large increases recorded in high frequency (15-50 Hz) activity and reductions in all other frequency bands. Various compounds have been used in an attempt to antagonise the changes in the ECoG. Chlorpromazine caused a slight shift in the dose-response curves as did chlordiazepoxide when used with phencyclidine. The GABA agonists, THIP and muscimol, had no effect on the stimulation of the ECoG. In contrast another presumed GABA agonist, baclofen, proved to be the most effective agent for blocking the stimulation induced by phencyclidine. The role of the GABAB receptor in the action of phencyclidine is discussed.     

Behavioural changes induced in conscious mice by intracerebroventricular injection of catecholamines, acetylcholine and 5-hydroxytryptamine.

1 In anaesthetized rats electrical stimulation of the intact cervical sympathetic nerve produced frequency-dependent lower eyelid contractions and tachycardia. 2 The tachycardia was caused by excitation of efferent fibres since it was equally evident in the pithed rat preparation, and the right nerve was more effective than the left. By contrast, no differences were seen between the responses to right and left vagal stimulation in either rats or rabbits. 3 Guanethidine inhibited both cardiac and eyelid responses, propranolol only the former and phentolamine only the latter, therby revealing the adrenergic nature of the nerves. Hexamethonium caused partial inhibition and the block was intensified by atropine. 4 The inferior eyelid of mice, guinea-pigs and rabbits as well as the nictitating membrane of rabbits and cats were contracted by cervical sympathetic nerve stimulation. In these species too, tachycardia occurred; this was more pronounced with the right than the left sympathetic nerve. The order of cardiac responsiveness was mouse greater than rat greater than guinea-pig greater than rabbit greater than cat. 5 In guinea-pigs histamine-induced bronchoconstriction was reduced by cervical sympathetic nerve stimulation. 6 That discrete cardiac pathways exist in the cervical sympathetic nerves is suggested by the reproducibility of the effects within any one species. The accessibility of the nerves greatly simplifies the examination of drugs in vivo on two different structures innervated by the sympathetic nervous system.     

Neurotoxic effects induced by intracerebral and systemic injection of paraquat in rats.

1 The neurotoxic effects elicited by paraquat after systemic and intracerebral injection were studied in rats. 2 Intrahippocampal microinfusion of paraquat (0.1 mumol) produced behavioural stimulation and electrocortical (ECoG) excitation followed, at 24 h, by multifocal brain damage. Similarly, microinfusion of paraquat (0.2-0.4 mumol) into the locus coeruleus, substantia nigra or into the raphe nuclei, where noradrenergic, dopaminergic and serotonergic neurons are present, respectively, elicited potent excitotoxic effects (n = 6 rats per dose and area). A lower dose (0.01 mumol) of the herbicide or injection of the vehicle (1.0 microliter) did not produce any behavioural, ECoG or neurodegenerative effect. 3 After systemic administration, paraquat (20 mg kg-1 s.c.) evoked limbic motor seizures and ECoG epileptogenic discharges; in 10 out of 15 treated rats neuronal cell death was observed in the pyriform cortex, but not in other brain regions. A dose of 5 mg kg-1 was ineffective. 4 Among the regions of the brain studied, high concentrations of paraquat were detected in the pyriform cortex 24 h after systemic administration (5.0 and 20 mg kg-1 s.c.) lower levels being observed in the caudate nucleus. 5 In conclusion, paraquat, given systemically or intracerebrally in rats produces neurodegenerative effects.     

Biochemical changes in different brain areas after toluene inhalation

Exposure to toluene causes both reversible and irreversible changes in the central nervous system. The effects of toluene inhalation on some specific enzymes and glutamate and GABA receptor binding in defined parts of the rat brain were studied following several exposure schemes. The activities of the transmitter synthesizing enzymes glutamic acid decarboxylase (GAD), choline acetyltransferase (ChAT) and aromatic amino-acid decarboxylase (AAD) were used as markers for permanent loss of neuronal activity. Catecholaminergic neurons showed a 50% reduction in the brain stem after 4 weeks exposure to 250 and 1000 ppm toluene. Following 500 ppm of toluene, 16 h/day for 3 months, a general increase in the activities was seen. This is most probably due to a reduction in total protein content, to which the activities were related. The neurotransmitters glutamate and GABA had their specific receptor binding increased in most of the brain areas studied, but decreased in some areas. The glial enzyme, glutamine synthetase, had its activity increased in the cerebellar hemisphere following 4 weeks exposure to 1000 ppm. This suggests that glial cells in the area may have proliferated, a frequent phenomenon following CNS damage.     

Behavioural, electrocortical and body temperature effects after intracerebral infusion of TRH in fowls.

In fowls TRH given into the III cerebral ventricle (0.25–5 μg) produced intense behavioural stimulation, electrocortical desynchronization and a slight increase in body temperature. In particular, an intense pattern of stereotyped head-neck movements, increase in locomotor activity, repeated and preening, vocalization, erection of the tail feathers and occasionally ‘escape responses’ were observed. This picture lasted for about 30 min and was followed by slight behavioural sedation during which stereotypies continued to occur but to a lesser extent. Similar increases in locomotor activity and stereotypies were evoked by infusing TRH into the hypothalamus whereas the unilateral microinfusion into the n. basalis or the n. mesencephalicus profundus, homologous to the mammalian striatum and s. nigra respectively, produced very intense stereotyped head-neck movements, wet-dog syndrome and vocalization. TRH given into the other areas of the brain (e.g. hyperstriatum, neostriatum, olfactory ventricle, eminentia basalis and lateral part of the mesencephalon) lacked effects on behaviour and body temperature. The effects of intraventricular infusion of TRH were antagonized by prior administration of haloperidol and spiperone whereas antagonists at α and β-adrenoceptors and at 5-HT receptors were ineffective. In addition, TRH reversed sedation induced by intraventricular α-methyl-p-tyrosine. Behavioural and body temperature effects of TRH were independent of its endocrine properties since these were not observed after systemic or intracerebroventricular injection of thyrotropin, triidothyronine and thyroxine. The increase in body temperature evoked by intracerebroventricular injection of TRH was due to activation of heat production and decrease in thermodispersive mechanisms.     

Behavioural changes induced by N,N-dimethyl-tryptamine in rodents.

1 N,N-Dimethyltryptamine (DMT) in pargyline pretreated rodents induced a dose-dependent behavioural syndrome consisting of hyperactivity, prostration and hindlimb abduction, mild tremor, Straub tail, retropulsion and jerking. 2 In rats pretreated with pargyline, the behavioural syndrome induced by DMT differed from that induced by L-tryptophan or quipazine, in the lack of forepaw treading and head-weaving and in the presence of only mild tremor. 3 The hyperactivity component of the DMT-induced behavioural syndrome in pargyline-pretreated mice was potentiated by cyproheptadine, methergoline, and mianserin, inhibited by cinanserin, haloperidol, pimozide, methiothepin and propranolol, and not affected by 501C67-sulphate and methysergide. 4 The maximal behavioural changes induced by DMT in rats, other than hyperactivity, were unaffected by pretreatment with cyproheptadine, methysergide, and cinanserin. However, propranolol reduced the intensity of all behavioural effects apart from body jerking, and methergoline decreased the duration of prostration. Phenoxybenzamine and haloperidol, in contrast, enhanced prostration. 5 DMT plus pargyline did not induce circling behaviour in mice with a unilateral 6-hydroxy-dopamine lesion of the nigro-striatal pathway. 6 The DMT-induced behavioural syndrome appears to consist of two components, (a) hyperactivity and (b) other behavioural changes. They differ in their response to drugs affecting brain monoamines. The hyperactivity component may be expressed via dopamine mechanisms, but the other behavioural changes are not. The two behaviours do not respond consistently to drugs believed to alter brain 5-hydroxytryptamine function.     

Methanol induced biogenic amine changes in discrete areas of rat brain: role of simultaneous ethanol administration

Alteration in the steady state level of brain biogenic amines produced by methanol differ considerably in rats when compared to the effects produced by ethanol. When ethanol and methanol were administered simultaneously in identical concentration, the effects produced by methanol were much more pronounced in the presence of ethanol. This could be attributed to the delay in the metabolism of methanol as ethanol competes with methanol for alcohol dehydrogenase enzyme activity. Hence, it is presumed that the effects produced by methanol seem to be primarily due to the direct action of methanol itself and not due to metabolic end products of methanol. It is also inferred that if methanol per se is going to produce any permanent damage in the central nervous system due to abnormal neurotransmitter behaviour, they cannot be prevented by treatment with ethanol.     

诺氟沙星侧脑室点燃大鼠癫痫及脑超微结构变化

目的:观察诺氟沙星对EEG的影响和对脑组织超微结构的毒性作用。方法:大鼠右侧脑室注射诺氟沙星150和300μg·kg~(-1)后,于皮层感觉运动区记录EEG并观察脑组织超微结构的变化。结果:大鼠EEG均出现痫样放电,两组大鼠右侧和左侧棘波发生时间为168±129,51±35s和276±138,118±65s。以注射侧较早发生,波形多变,幅度和频率逐渐增大,并伴肢体抽搐的行为学改变。电镜下,300μg·kg~(-1)组大鼠双侧大脑皮层、海马及小脑均有明显的神经元变性,包括高尔基复合体、粗面内质网及神经毡的髓样变性、细胞质肿胀、细胞核及染色质溶解、胶质细胞坏死等,并出现亮神经元和暗神经元改变,以暗神经元为著。结论:诺氟沙星点燃癫痫后,大鼠脑组织超微结构受到广泛损伤。     

Influence of paraquat on dopaminergic transporter in the rat brain

Selective toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a parkinsonism inducing compound, is well known to be related to an uptake of its active metabolite MPP+ into dopaminergic neurons by dopamine transporter (DAT). The aim of the present study was to examine whether paraquat, a commonly used herbicide, which is an 1-methyl-4-phenyl-pyridinium ion (MPP+) analogue, affects DAT in vivo in rats. Paraquat administered at a dose of 10 mg/kg ip decreased the binding of [3H]GBR 12,935 to DAT measured by quantitative autoradiography in the dorsal and ventral caudate-putamen, but not in the substantia nigra pars compacta. Moreover, this compound increased the level of 3-methoxytyramine (3-MT) and 3-MT/dopamine ratio in the anterior and posterior caudate-putamen measured by HPLC with electrochemical detection. No other alterations in the levels of dopamine and its metabolites were found in the caudate-putamen and substantia nigra. The present study seems to suggest that systemic paraquat administration affects striatal DAT and dopamine metabolism in the nigrostriatal neurons in rats which may be crucial for its neurotoxic effects on dopaminergic neurons.     

Behavioural and electrocortical power spectrum effects of 5-methoxytryptoline and other analogs after intraventricular administration in rats

The behavioural and electrocortical power spectrum effects of tryptoline and the 5-hydroxy and 5-methoxy derivatives were studied after microinjection of the drugs into the third cerebral ventricle in freely moving rats. The three compounds produced a dose-dependent desynchronication in electrocortical activity with a concomitant syndrome of behavioural stimulation. The most potent compound was 5-methoxytryptoline, already active at 4 nmol. When given into the third cerebral ventricle, 5-methoxytryptoline antagonized the sedation and hypothermia induced by reserpine. The relative order of potencies was 5-methoxytryptoline greater than 5-hydroxytryptoline greater than tryptoline. Melatonin, the 5-methoxy-N-acetyl derivative of serotonin, when injected into the third cerebral ventricle, did not produce desynchronization and elicited only mild sedation. The high potency of 5-methoxytryptoline following injection into the third cerebral ventricle and the relative order of potencies with 5-hydroxytryptoline and tryptoline is compared to the affinity of these compounds for the modulatory site of the serotonin transporter which was labelled with [3H]imipramine or [3H]paroxetine.     

Dynamics of experimental vasogenic brain oedema in the rat: changes induced by adrenergic drugs

The effects of adrenergic drugs on the formation and resolution of cerebral oedema in a rat model of cold-induced vasogenic brain oedema were studied. Evans blue dye extravasation, water content and ultrastructural alterations (pinocytotic vesicle formation in capillary endothelial cells and apparent water accumulation in the brain parenchyma) were evaluated in parietal cortex. Previous administration of the alpha-adrenoceptor antagonist phenoxybenzamine produced a reduction of Evans blue extravasation and water content, diminished vesicle formation and reduced water accumulation. Previous administration of the beta2-adrenoceptor agonist clenbuterol reduced Evans blue extravasation and water content, but did not change vesicle frequency. The effects of clenbuterol on Evans blue passage to the brain were blocked by timolol (beta-adrenoceptor antagonist) but not by metoprolol (selective beta1-adrenoceptor antagonist). When given after the application of cold, clenbuterol was also able to reduce Evans blue and water content in the brain. Isoprenaline (beta-adrenoceptor agonist that does not cross the blood-brain barrier) showed a reduction in Evans blue extravasation only when given intracerebroventricularly. Vinblastine (a drug that prevents vesicle formation) produced a reduction of the amount of pinocytotic vesicles. We conclude that there is an influence of the central adrenergic nervous system on the formation and/or resolution of vasogenic brain oedema and that the alterations on water movement and Evans blue transport mediated by adrenergic drugs seem to be due, at least in part, to alterations of pinocytotic activity in capillary endothelial cells.     

Distribution of ytterbium-169 in rat brain after intravenous injection

It is well known that lanthanides have come into extensive and rapid use in a number of fields. As a result, more and more lanthanides are getting into the environment and food chains. However, the distributions of lanthanides in brain are not yet very clear. In this study, adult Sprague-Dawley male rats were intravenously injected with 0.5 ml of 169YbCl3 solution (containing 10 microg Yb). The brains were perfused with saline to minimize the blood influence. The radioactivities of 169Yb in the five brain regions (hypothalamus, cerebellum, hippocampus, corpus striatum and cerebral cortex) were counted. The results suggested that Yb did enter into the brain. Though only about 0.005% of the given dose was accumulated in the brain, Yb seemed to remain in the brain for long time. The highest specific activities were observed in the hypothalamus, hippocampus and cerebellum.     

Dopaminergic metabolism in various rat brain areas after L-dopa loading

The time course of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT) and 3-methoxytyrosine (3-O-Medopa) concentrations in rat brain after treatment with L-dopa + benserazide has been investigated in the striatum, hypothalamus, hippocampus and cerebellum. These areas were selected for their different dopaminergic activities. After L-dopa loading, DA, DOPAC and HVA were increased in all the structures, but the largest increases were in those tissues with the less dopaminergic activity, while 3-MT increased in the hypothalamus, hippocampus and cerebellum but was lowered in striatum. 3-O-Medopa, which is the direct product of the O-methylation of L-dopa, did not show any specific distribution. The data provide evidence that the striatum, by feed-back mechanisms and specific enzymatic activity, is able to ensure a better regulation of dopaminergic activity than the other structures, thereby overcoming excess L-dopa.