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Biomedical subjects

J Luthman

Publications and source records attributed to J Luthman.

At least 73 records · Page 4Linked to original sources
PubMed1990

No apparent difference in the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the sympathetic system in NMRI and C57 BL/6 mice.

The parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to possess marked species as well as strain differences in toxicity on central catecholaminergic systems. In the present study the effects on the peripheral sympathetic nervous system following treatment with MPTP, as well as its metabolite 1-methyl-4-phenylpyridine (MPP+) and the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) were studied in mice of the NMRI and C57 BL/6 strains, two strains that possess marked difference in MPTP toxicity on central catecholaminergic neurons. No strain differences in the depletions of noradrenaline (NA) in iris and heart auricula and of NA and dopamine (DA) in superior cervical ganglion or in the reduction of the in vitro [3H]NA uptake in iris or heart auricula were found following MPTP treatment (2 X 40 mg/kg s.c., 2 and 7 days). Treatment with the NA uptake blocker desipramine (DMI) did not affect the MPTP-induced NA depletion in either strain. Following treatment with MPP+ (30 mg/kg i.v., 7 days) no differences in the two strains were seen on the reduction of NA levels in iris and heart auricula or decrease in [3H]NA uptake. In addition, no differences were found on NA levels in iris and heart auricula after 6-OHDA treatment (15 mg/kg i.v., 7 days). The data indicate that in the NMRI and C57 BL/6 mice peripheral NA neurons do not possess any notable strain difference in the vulnerability to MPTP or in the mechanism of action of MPTP.

1-Methyl-4-phenylpyridinium↗
PubMed1990

Structural and neurochemical effects in mouse cerebellum following neonatal methylazoxymethanol and 6-hydroxydopamine treatment.

The effects of neonatal treatment with the antimitotic agent methylazoxymethanol and the catecholamine neurotoxin 6-hydroxydopamine on cerebellar morphology and monoamine innervation in the N.M.R.I. mouse has been studied. Methylazoxymethanol (25 mg/kg s.c.) treatment induced a cerebellar weight reduction of 40% as observed in the adult stage, while other CNS regions analysed were unaffected. An obvious atrophy of the cerebellar cortex was found, with an irregular distribution of the Purkinje cells, while Bergmann glia fibers deviated from their normal radial configuration and showed a tendency to form clusters. A 65% increase of tyrosine hydroxylase immunoreactive fiber density was found in the cerebellar cortex and 3H-5-hydroxytryptamine in vitro synaptosomal uptake was increased by 55%. Noradrenaline and 5-hydroxytryptamine concentrations in the cerebellum increased by 50 and 30%, respectively, whereas the total content of both neurotransmitters in cerebellum was approximately unchanged after methylazoxymethanol treatment. A significant reduction in total cerebellar in vitro binding of 3H-WB-4101 and 3H-dihydroalprenolol was also found, indicating compensatory receptor alterations following methylazoxymethanol treatment. The effect of combined treatment of methylazoxymethanol and the neurotoxin 6-hydroxydopamine (50 mg/kg s.c., day 1) showed a very pronounced reduction of noradrenaline concentration in cortex cerebri, while the noradrenaline concentration in cerebellum was increased by 185% and the tyrosine hydroxylase immunoreactive fiber density by 125%, indicating an additional relative hyperinnervation of cerebellar noradrenaline fiber due to a "pruning effect" of the 6-hydroxydopamine treatment. The results imply a relatively rigid development of terminal arborization of central nervous system monoamine neurons, relatively independent of neuronal and glial arrangement in the target area.

Animals↗
PubMed1990

Studies on brain monoamine and neuropeptide systems after neonatal intracerebroventricular 6-hydroxydopamine treatment.

In order to study the effects of a neonatal dopamine lesion on dopaminergic, serotonergic and peptidergic systems, Sprague-Dawley rats were treated by intracerebroventricular administration of 6-hydroxydopamine (100 micrograms, days 3 and 6) following desipramine pretreatment (25 mg/kg s.c.). At 60-70 days postnatally a profound reduction of dopamine- and 3,4-dihydroxyphenylacetic acid levels was found in striatal and limbic forebrain regions concomitant with an extensive loss of tyrosine hydroxylase-immunoreactive fibers, while no significant alteration in noradrenaline levels was seen. A marked loss of tyrosine hydroxylase-immunoreactive cell profiles was also observed in the substantia nigra and ventral tegmental area in mesencephalon. In striatum, but not in other regions analysed, an almost 100% increase in serotonin levels and serotonin-immunoreactive fiber density was observed following 6-hydroxydopamine treatment. However, the number of serotonin-immunoreactive cell profiles in the median and dorsal raphe nuclei was not altered. The 6-hydroxydopamine treatment also led to reductions in substance P levels in striatum, nucleus accumbens and ventral mesencephalon. The cholecystokinin level in nucleus accumbens and neurotensin level in ventral mesencephalon were also reduced. A neonatal intracerebroventricular 6-hydroxydopamine treatment thus leads to a lesion of dopamine neurons in the mesencephalon with extensive loss of dopamine fibers in several forebrain areas, while localized serotonin fiber sprouting is induced in striatum. Furthermore, concomitant reductions of the levels of peptides related to the dopamine system occur following the 6-hydroxydopamine treatment. Behavioral disturbances such as hyperactivity and cognitive deficiencies occurring after a dopamine lesion early in life might therefore be due to plastic alterations in several different transmitter/neuromodulator systems as a direct or indirect consequence of the lesion.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

The biological response of selenium in individual erythrocytes and GSH-Px in lambs fed sodium selenite or selenium yeast.

Twenty Swedish Landrace lambs were divided randomly into two equal groups, group I and group O. Group I received approximately 0.1 mg selenium as sodium selenite per day and group O 0.1 mg selenium as selenium in yeast per day. The animals were fed per day 1.2-1.5 kg of hay and 0.3 kg of a commercial concentrate supplemented with vitamins and minerals. The trial lasted 3.5 months. As monitored by micro particle induced X-ray emission (mu-PIXE), the number of selenium bearing erythrocytes increased faster in group O than in group I indicating some difference in the metabolism of inorganic and organic selenium. During the trial the concentration of sulphur decreased in the erythrocytes in group O. The reason for this is not known. The zinc and copper concentrations of individual erythrocytes were unaltered. The blood GSH-Px activity increased at the same rate in the two groups indicating that selenium as sodium selenite and selenium in yeast was about equally available. The rate of growth in the two groups was almost the same and a significant difference in the final weight was not observed.

Animals↗
PubMed1990

Plant-derived neurotoxic amino acids (beta-N-oxalylamino-L-alanine and beta-N-methylamino-L-alanine): effects on central monoamine neurons.

In the present study the subacute effects of beta-N-oxalylamino-L-alanine (BOAA) and beta-N-methylamino-L-alanine (BMAA) on CNS monoamine neurons in rats were investigated following intracisternal injections or local intracerebral administration into substantia nigra. In vitro effects of BOAA and BMAA on high-affinity synaptosomal uptake of dopamine (DA), noradrenaline (NA), and serotonin (5-HT) were also examined. Intracisternal administration of BMAA decreased NA levels in hypothalamus, whereas no effects were seen on DA or 5-HT levels. Following intranigral injections of BOAA, NA levels tended to decrease in several regions, whereas the DA levels and the levels of DA metabolites were unaffected in all regions analyzed. Loss of tyrosine hydroxylase (TH) immunoreactivity in the intranigral injection sites and the presence of TH-immunoreactive pyknotic neurons near the borders of the injection sites were observed following both BOAA and BMAA treatments. Furthermore, substance P-immunoreactive terminals in substantia nigra pars reticulata were also found to have disappeared within the lesioned area following either BOAA or BMAA injections. Incubations with both BOAA and BMAA (10(-5) M) reduced high-affinity [3H]NA uptake in cortical synaptosomes to 69% and 41% of controls, respectively, whereas the striatal high-affinity [3H]DA uptake and the cortical high-affinity [3H]5-HT uptake were unaffected by BOAA or BMAA. The results demonstrate that both BOAA and BMAA can affect central monoamine neurons, although the potency and specificity of these substances on monoamine neurons when administered acutely into cerebral tissue or liquor cerebri seem to be low. However, the in vitro studies indicate selective effects of both compounds on NA neurons in synaptosomal preparations.

Alanine↗
PubMed1989

Selective lesion of central dopamine or noradrenaline neuron systems in the neonatal rat: motor behavior and monoamine alterations at adult stage.

Different parameters of motor behavior (locomotion, rearing and total activity counts) were studied in the adult rat following neonatal intracisternal 6-hydroxydopamine (6-OHDA, 50 micrograms) treatment combined with noradrenaline (NA) uptake blocker (desipramine) or dopamine (DA) uptake blockers (amfolenic acid or GBR 12909) to obtain selective DA or NA lesions respectively. At 61-65 days of age, selective DA-lesioned animals showed an initial decrease in spontaneous motor behavior at test days 1 and/or 2, while at test days 4 and 5 hyperactivity was observed. However, following amfolenic acid or GBR 12909 pretreatment leading to a selective NA lesion, no difference in spontaneous motor behavior was seen on any of the 5 test days. Determination of regional brain levels of NA and DA confirmed the type of lesion predicted from the various pretreatments with selective uptake blockers. These data suggest that changes in motor behavior in the adult rats, following neonatal 6-OHDA treatment, are specifically related to a DA-denervation, whereas an NA lesion does not seem to influence the spontaneous motor behavior. However, following the selective DA lesion, significant increases of serotonin levels in striatum and cerebellum were observed, while following selective NA lesions an increase of cerebellar NA levels was found concomitant with drastic reductions of NA levels in frontal cortex and spinal cord.

Aging↗
PubMed1989

Effects of d-amphetamine and methylphenidate on hyperactivity produced by neonatal 6-hydroxydopamine treatment.

Neonatal intracisternal administration of 6-hydroxydopamine (6-OHDA, 50 micrograms on day 1 after birth) caused a marked hyperactivity when the rats were tested as adults. These rats also showed severe DA depletions in striatum and nucleus accumbens. Pretreatment with the noradrenaline (NA) uptake inhibitor desipramine provided protection against NA depletion in frontal cortex and nucleus accumbens. Pretreatment with DA uptake inhibitors, amfolenic acid or GBR 12909, before 6-OHDA, provided full protection against DA depletion but produced marked NA depletion in frontal cortex. These rats did not demonstrate any degree of hyperactivity. Low doses of d-amphetamine (0.25 mg/kg SC) or methylphenidate (1 mg/kg SC) reversed the hyperactivity in DA-depleted rats but increased motor activity in vehicle-treated and NA-depleted rats. Higher doses of d-amphetamine (1 mg/kg) or methylphenidate (4 mg/kg) produced potentiated levels of locomotion but attenuated levels of rearing in DA-depleted animals. The results further suggest the utility of the neonatal DA lesion in rats as a potential animal model for derivation of therapeutic agents that may be efficacious in the treatment of the hyperkinetic syndrome.

Animals↗
PubMed1989

A substrate of the cell-attachment sequence of fibronectin (Arg-Gly-Asp-Ser) is sufficient to promote transition of arterial smooth muscle cells from a contractile to a synthetic phenotype.

Extracellular matrix components strongly influence the differentiated properties of isolated rat arterial smooth muscle cells during in vitro cultivation. The attachment and spreading of the cells on a substrate of fibronectin or a 105-kDa cell-binding fragment of fibronectin are accompanied by a structural and functional transformation, referred to as a transition or modulation from a contractile to a synthetic phenotype. Here, the ability of the cell-attachment sequence of fibronectin, Arg-Gly-Asp-Ser (RGDS), to promote this process was studied. The results demonstrate that freshly isolated smooth muscle cells attached to a substrate of the synthetic peptide Gly-Arg-Gly-Asp-Ser-Cys (GRGDSC) in a specific manner and as well as to substrates of fibronectin and the 105-kDa fragment. Subsequent spreading of the cells on the peptide substrate followed the same kinetics and was as extensive as on fibronectin, even if protein synthesis was blocked by treatment of the cultures with cycloheximide. Like fibronectin, the peptide substrate induced formation of actin filament bundles, again without ongoing protein synthesis. Moreover, it was as efficient as fibronectin in supporting the transition of the cells from a contractile to a synthetic phenotype as analyzed by electron microscopy. Antibodies against the beta subunit of the fibronectin receptor interfered with the attachment, spreading, and fine structural reorganization of the cells in a similar manner on substrates of fibronectin, the 105-kDa fragment, and GRGDSC. Taken together, the findings indicate that the cell-attachment sequence (RGDS) mimics intact fibronectin in promoting a change in the differentiated properties of arterial smooth muscle cells and does so by interacting with a cell surface receptor for fibronectin.

Actins↗
PubMed1989

Capsaicin treatment to developing rats induces increase of noradrenaline levels in the iris without affecting the adrenergic terminal density.

The effects of administration of capsaicin to developing and adult Sprague-Dawley rats on substance P-containing primary afferent and peripheral adrenergic nerves were analysed by histochemical and neurochemical techniques. In control rats a relatively dense innervation with substance P-immunoreactive fibers was seen in the iris, while 10 weeks after a single neonatal injection of capsaicin (50 mg/kg s.c.) a moderate loss of substance P-immunoreactive nerve fibers was observed. The substance P level was decreased by 60%, while the noradrenaline level, 3H-noradrenaline uptake in vitro and the noradrenaline nerve density were unaltered. Repeated injections of capsaicin (2 x 50 mg/kg, 3 x 20 mg/kg s.c.) for 5 weeks to developing rats led to a very marked decrease of the substance P level and an almost complete disappearance of substance P-immunoreactive fibers in the iris, when analysed at 10 weeks of age. The noradrenaline level in the iris was significantly increased (+42%), while no significant changes in noradrenaline level were observed in heart auricula or superior cervical ganglion. The uptake in vitro of 3H-noradrenaline in irides and heart auriculae, as well as the noradrenaline terminal density in the dilator plate and surrounding blood vessels in the iris, were unaffected by repeated capsaicin treatment to developing rats. Capsaicin administration to adult rats (50 mg/kg s.c.), leading to a profound decrease in substance P, did not affect the noradrenaline levels at 24 hr after the injections. The results indicate that an extensive sensory denervation with capsaicin during development can induce an increase of noradrenaline levels in sympathetic nerve terminals in a target area (rat iris) with a rich SP-ergic sensory innervation, although the sympathetic terminal density is not influenced. Furthermore the increase in noradrenaline seems to require an extensive loss of SP-immunoreactive fibers and not solely a reduction of SP levels.

Adrenergic Fibers↗
PubMed1989

Concentrations of sulphadimidine, oxytetracycline and penicillin G in serum, synovial fluid and tissue cage fluid after parenteral administration to calves.

Drug concentrations in serum, synovial fluid and tissue cage fluid (TCF) in calves were measured after single i.m. doses of oxytetracycline hydrochloride (OTC), procaine penicillin G (PPG) and potassium penicillin G (KPG) and single i.v. doses of sulphadimidine (SDM) and OTC. For all drugs, concentration-time curves in serum and synovial fluid were not identical but they had similar profiles, with peak levels occurring at about the same time. Concurrent concentrations were lower in synovial fluid than in serum. For each drug, elimination half-lives from synovial fluid and from serum were similar, except for penicillin G after KPG administration which had a significantly longer half-life from synovial fluid than from serum (P less than 0.05). Of the two penicillin G preparations, PPG gave a significantly higher synovial fluid:serum area under curve (AUC) ratio than did KPG; 0.76 +/- 0.10 and 0.54 +/- 0.12, respectively (P less than 0.05). For OTC, the synovial fluid:serum AUC-ratio was 0.33 +/- 0.12 after i.m. and 0.34 +/- 0.08 after i.v. administration. Drug concentration-time curves of TCF had different profiles compared with serum, with relatively low and delayed peak levels and slow elimination from TCF. TCF:serum AUC-ratios did not differ significantly for i.m. and i.v. administration of OTC; 0.10 +/- 0.10 and 0.19 +/- 0.03 respectively (P greater than 0.05). Potassium penicillin G (KPG), however, gave a significantly higher TCF:serum AUC-ratio than PPG; 0.55 +/- 0.21 and 0.19 +/- 0.07, respectively (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Studies on the bioavailability of tetracycline chloride after oral administration to calves and pigs.

The serum concentrations of tetracycline (TC) were studied in calves after administration in the milk replacer and in pigs after administration in feed and drinking water. Serum concentrations of potential therapeutic value (greater than 1 microgram/ml) were obtained in the calves when TC was fed in the milk replacer at a dose of 25 mg/kg body weight twice daily. Significantly higher serum concentrations were achieved after a single oral dose (50 mg/kg) given in the milk replacer than afer the same dose given as a water drench four hours after the first daily milk feeding. The difference was explained by the fact that the calves probably consumed their daily amount of concentrate and an unknown amount of hay previous to the drench. Earlier studies showed that concentrates reduce the bioavailability of tetracyclines more than a conventional milk replacer. Serum concentrations of potential therapeutic value could not be achieved in the pigs in spite of recommended doses. The TC concentrations in the water were 400 mg/l and 800 mg/l. Tetracycline did not appear to influence the water consumption. Serum concentrations were highest in the evening and fell during the night. The highest levels after 400 mg/l water were 0.30-0.47 microgram/ml. The corresponding levels after 800 mg/l were 0.65-1.15 micrograms/ml. It was concluded that feed seriously reduced the bioavailability of TC. The influence of feeding was demonstrated in a single dose study. Fasted animals showed much higher serum levels than non-fasted ones. Very low and constant serum levels (about 0.2mg/ml occurred when TC mixed in the feed at a concentration of 1,00 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Immunohistochemical study of neurochemical markers in gingiva obtained from periodontitis-affected sites.

Immunohistochemical methods have been used to study the occurrence of neuronal markers in human gingiva from periodontitis-affected sites. In periodontitis-affected buccal gingiva densely distributed neurofilament (NF)-immunoreactive (IR) fiber bundles were observed in the deeper parts of the propria, while NF-IR single fibers occurred in the superficial propria and occasionally in the buccal epithelium. Periodontitis-affected gingiva obtained from interproximal sites showed only sparsely distributed NF-IR fibers. Single nerve fibers immuno-reactive to the peptides substance P and calcitonin gene-related peptide occurred close to or within the epithelium in both buccal and interproximal gingiva. Around blood vessels neuropeptide Y-, peptide histidine-isoleucine amide- and vasoactive intestinal polypeptide-IR fibers were occasionally observed, while clusters of gamma-melanocyte-stimulating hormone-IR cells were found in the propria, in addition to gamma-melanocyte-stimulating hormone IR nerve fibers. Somatostatin-IR dendritic cells were seen in epithelium and propria of buccal and interproximal gingiva, although a high variability in the number of SOM-IR cells was observed. All neuronal markers studied showed a similar distribution in material obtained from young patients with clinically healthy gingivae, although the number of NF-IR fibers in the propria in these subjects was lower. The results demonstrate that in gingiva obtained from periodontitis-affected sites several different biologically active peptides occur in both nerve fibers and cells. At least some of these substances could possible play a role in the inflammatory process. However, since clinically normal gingiva was shown to contain nerve fibers and cells expressing immunoreactivity to the substances studied, no unique periodontitis-induced expression of the neuronal markers studied was found. Thus, any alteration of these substances during the periodontitis process remains to be elucidated.

Adolescent↗
PubMed1989

The influence of flunixin on the response to Salmonella typhimurium endotoxin in calves.

The effects of intravenous injection of 0.5 microgram/kg body weight of Salmonella typhimurium endotoxin were studied in calves. The injection was followed by ruminal stasis and general dullness. The clinical signs disappeared within 24 hours. The injection was followed by a tremendous increase in the plasma level of 15-ketodihydro-PGF2 alpha, the main metabolite of PGF2 alpha. The injection was also associated with a profound leukopenia and significant decreases in the serum levels of iron, zinc and calcium. In order to study the role of prostaglandin (PG) for the development of endotoxin-induced changes a group of calves was pretreated with flunixin, a potent cyclo-oxygenase inhibitor, at a dose of 2.2 mg/kg body weight. Flunixin inhibited the PG release completely, but did not influence the other responses to endotoxin. The pyrogenic response to endotoxin was very moderate and it was suggested that fever is not the most suitable parameter for monitoring endotoxin effects in calves. The studied blood parameters (15-ketodihydro-PGF2 alpha, iron, zinc, calcium and the number of leukocytes) appeared to be much more sensitive.

Animals↗
PubMed1988

Immunohistochemical studies of the neurochemical markers, CGRP, enkephalin, galanin, gamma-MSH, NPY, PHI, proctolin, PTH, somatostatin, SP, VIP, tyrosine hydroxylase and neurofilament in nerves and cells of the human attached gingiva.

Punch biopsies were obtained from the buccal gingiva of the lower third molars. Thin nerve fibres, immunoreactive for calcitonin gene-related peptide (CGRP) or substance P (SP), with possible sensory function, were found in the propria often close to the epithelium, sometimes even penetrating into the basal layers. gamma-Melanocyte stimulating hormone (gamma-MSH)-like immunoreactivity was found in sparsely distributed single cells (except in one specimen containing a dense infiltration), resembling neutrophilic granulocytes of the propria. gamma-MSH was present in several single smooth axons and in thick axon bundles of the propria. Surrounding the blood vessels, neuropeptide Y (NPY), tyrosine hydroxylase (TH), vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine amide (PHI) immunoreactive nerve fibres were observed. NPY and TH-positive fibres probably represent sympathetic nerve terminals and VIP/PHI-immunoreactive ones may have a parasympathetic function. Papillae of the propria contained VIP-positive fibres not obviously related to blood vessels. The distribution in papillae of PHI-like immunoreactivity was similar but the PHI-positive reaction was also present in a few cells of the propria, especially near blood vessels. Somatostatin (SOM)-positive reaction occurred in a few dendritic-type cells near or in the epithelium and single nerve fibres close to the epithelium. Several thick axon bundles of the propria contained neurofilament (NF)-immunoreactive material. Some thin NF-fibres were found in the papillae and some seemed to penetrate into the epithelium. No galanin, methionine-enkephalin, parathyroid hormone or proctolin immunoreactive material was found. The rather rich content of several neuropeptides in human attached gingiva, as well as other neurochemical markers, is probably associated with sensory and autonomic functions.

Adult↗
PubMed1988

Exogenous GM1 ganglioside and thyrotropin-releasing hormone do not affect survival rate of spinal motorneurons and number of ventral root myelinated fibers following early postnatal sciatic nerve transection.

Treatment with gangliosides or thyrotropin-releasing hormone has been shown to stimulate structural and functional recovery that follows mechanical or chemical lesions in the nervous system. We studied the possible effects of the ganglioside GM1 and thyrotropin-releasing hormone on the survival rate of spinal motorneurons after sciatic nerve transection at the age of 1 week in the rat. GM1 (30 mg/kg body weight, i.p.) was administered 24 and 1 h before and once daily for 2 weeks after transection. TRH (2 mg/kg body weight, i.p.) was administered 1 h before, at 2, 16, and 24 h, and thereafter once daily for 7 days after transection. Nine weeks postlesion, the number of motorneuron profiles labeled by retrograde transport from the proximal stump of the sciatic nerve was counted and measured using a computerized image analysis system, and the number of myelinated axons in ventral roots L4 and L5 was estimated. Compared with controls, no significant effects of GM1 or hormone treatment were observed with regard to the number, diameter, and area of motorneuron profiles and the number of ventral root myelinated axons ipsilateral to sciatic nerve injury. The results may indicate principal differences between various lesions and/or metabolic reactions following a lesion of developing and adult neurons. The present lesion model with an intense axon reaction and extensive nerve cell death does not seem to respond to administration of exogenous GM1 or thyrotropin-releasing hormone.

Animals↗
PubMed1988

Neonatal 6-hydroxydopamine-induced dopamine depletions: motor activity and performance in maze learning.

Three experiments were performed to study the effect of dopamine (DA) depletions, induced by neonatal intracerebroventricular (ICV) treatment with 6-hydroxydopamine (6-OHDA), upon measures of spontaneous motor activity. Instrumental learning for food reward in an Olton radial arm maze and escape learning from a large, circular water maze were studied also. Motor activity was measured by direct observation of rats in a modified radial arm maze and by use of automated test cages equipped with photocell devices. 6-OHDA-treated rats demonstrated considerable and long-lasting locomotor (ambulation) activity and total activity increases. 6-OHDA-treated rats showed notably less rearing activity than the vehicle-treated rats during the initial 20 min of each 60-min test period. However, over the second half of these 60-min test periods, the 6-OHDA-treated rats demonstrated significantly more rearing activity than the vehicle-treated rats. In the acquisition of the running response, to obtain the 8 food pellets placed in each of the 8 arms of the radial arm maze, 6-OHDA rats showed a retarded acquisition, as measured by the latency and number of arms visited to acquire all eight pellets. 6-OHDA-treated rats failed completely to acquire the Morris-type swim maze task by which they were required to locate a platform just under the water surface in a circular water tank. The neurochemical assays indicated severe DA depletion in several forebrain regions. The present findings add to existing indications of the potential of this DA depletion condition as an animal model of the minimal brain dysfunction syndrome.

Animals↗
PubMed1988

Time course of MPTP-induced degeneration of the nigrostriatal dopamine system in C57 BL/6 mice.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a parkinsonism-inducing dopamine (DA) neurotoxin most effective in primates. MPTP also causes a degeneration of both perikarya and axon terminals of the nigrostriatal DA neurons in C57 BL/6 mice. The time courses of the changes in tyrosine hydroxylase immunoreactive objects, endogenous DA concentrations and specifically bound 3H-mazindol as markers of the integrity of DA neurons were studied in substantia nigra and striatum of adult C57 BL/6 mice, after systemic treatment with MPTP or intranigral injections of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA). A rapid decrease in the three parameters studied was found in the substantia nigra during the first 2 days after MPTP-treatment while the MPTP-induced effects in the striatum were more protracted and maximal reduction was observed 7 days after MPTP. A basically similar pattern was found when studying the 6-OHDA-induced anterograde degeneration of the nigrostriatal system. These results indicate that in C57 BL/6 mice, MPTP primarily destroys the DAergic perikarya with a subsequent anterograde degeneration of the striatal axon terminals, although a limited rapid destruction of some striatal terminals cannot be excluded.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗