Search PubMed⌕ Search

Biomedical subjects

G Jonsson

Publications and source records attributed to G Jonsson.

At least 37 records · Page 2Linked to original sources
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

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

Synthesis and release of dopamine in rat brain: comparison between substantia nigra pars compacts, pars reticulata, and striatum.

Dopamine (DA) is synthesized and released not only from the terminals of the nigrostriatal dopaminergic neuronal pathway, but also from the dendrites in the substantia nigra. We have investigated the regulation of the DA turnover, the DA synthesis rate, and the DA release in the substantia nigra pars compacts (SNpc) and pars reticulata (SNpr) in vivo. As a measure of DA turnover, we have assessed the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid. As a measure of the DA synthesis rate, we have determined the 3,4-dihydroxyphenylalanine accumulation after inhibition of aromatic L-amino acid decarboxylase by 3-hydroxybenzylhydrazine. As a measure of DA release, we have investigated the disappearance rate of DA after inhibition of its synthesis by alpha-methyl-p-tyrosine and the 3-methoxytyramine accumulation following monoamine oxidase inhibition by pargyline. Both the DA turnover and the DA synthesis rate increased following treatment with the DA receptor antagonist haloperidol and decreased following treatment with the DA receptor agonist apomorphine in the SNpc and in the SNpr, but the effects of the drugs were less pronounced than in the striatum. gamma-Butyrolactone treatment, which suppresses the firing of the dopaminergic neurons, increased the DA synthesis rate in the striatum (165%), but had no such effect in the SNpc or SNpr. Haloperidol, apomorphine, and gamma-butyrolactone increased, decreased, and abolished, respectively, the DA release in the striatum, but the drugs had no or only slight effects on the alpha-methyl-p-tyrosine-induced DA disappearance and on the pargyline-induced 3-methoxytyramine accumulation in the SNpc or SNpr. Taken together, these results indicate that the DA synthesis rate, but not the DA release, are influenced by DA receptor activity and neuronal firing in the SNpc and SNpr. This is in contrast to the situation in the striatum, where both the DA synthesis rate and the DA release are under such control.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Adaptive changes in alpha-2 adrenoceptor mediated responses: analgesia, hypothermia and hypoactivity.

The acute effects of the alpha-2 adrenoceptor agonists, clonidine and guanfacine, upon antinociception, hypothermia and motor activity were compared under conditions of receptor antagonism, denervation, and chronic administration of a tricyclic antidepressant compound. The analgesic actions of clonidine and guanfacine were antagonised by idazoxan, an alpha-2 receptor antagonist, but potentiated by pretreatment with the noradrenaline neurotoxin DSP4, and attenuated by chronic treatment with desipramine (DMI). Clonidine- and guanfacine-induced hypothermia was antagonised by idazoxan, potentiated by prior treatment with DSP4 and attenuated by chronic administration with DMI. Both clonidine and guanfacine produced decreases in motor activity that were attenuated by idazoxan but unaffected by prior DSP-4 treatment. Chronic DMI administration also attenuated clonidine-induced hypoactivity but potentiated guanfacine-induced hypoactivity. These diverse results describe both similar and differential adaptive mechanisms modulating the functional effect of alpha-2 receptor systems in the central nervous system.

Adaptation, Physiological↗
PubMed1989

Deficits in reaction times and movement times as correlates of hypokinesia in monkeys with MPTP-induced striatal dopamine depletion.

1. We quantitatively assessed deficits in the initiation and execution of arm movements occurring after destruction of nigrostriatal dopamine neurons by systemic administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) (Sigma). Three monkeys performed a reaction time task in which they reached toward a single and constant target for food reward. 2. After administration of MPTP, all three monkeys showed hypokinesia necessitating dopamine precursor or receptor agonist treatment. The partial recovery of one animal from initial akinesia after 19 days permitted discontinuation of dopaminergic drug therapy, although marked hypokinesia remained present. The two other animals displayed additional, intermittent phases of rigidity and activation tremor and needed continuous dopaminergic drug therapy for most of the postlesion period. 3. Administration of MPTP significantly prolonged EMG reaction time in prime mover muscles and arm movement reaction time by 47-225% and 18-129%, respectively, on the six sides of the three animals, compared with control measurements before the lesion. EMG and arm movement reaction time increased over consecutive trials in most sessions comprising 110-130 movements, the first 20 movements showing almost normal values. The delay time between onsets of EMG and arm movement showed unsystematic changes. These deficits in movement initiation were observed both with and without dopamine precursor therapy. They lasted during the whole testing period of several months. 4. Linear correlations between arm movement onset and EMG onset in the two prime mover muscles, the extensor digitorum communis and the biceps, showed coefficients of mostly 0.7-0.9, both before and after MPTP. These data suggest that the temporal relationship between onsets of arm movement and EMG were not substantially affected by MPTP. 5. Arm movement time was divided into two phases. The duration of movement between the resting key and the target, a small food-containing box located ahead of the animal, was denoted as reaching movement time. The following hand manipulation inside the food box was measured as box movement time. After MPTP, both measures were significantly prolonged by 10-103% and 12-251%, respectively, on the six sides of the three monkeys. These deficits in movement execution were observed both with and without dopaminergic drug therapy and during the whole testing period. 6. Task performance after MPTP treatment was studied in one monkey in the absence of dopaminergic drug therapy. EMG and arm movement reaction times recovered partially over several weeks, while the prolongations in reaching and box movement times remained unchanged.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

Food and nutrient intakes in Swedish diabetic children.

Food and energy intakes in diabetic children, 7-9 and 12-14 years of age, were studied by the 7-d record method. The mean duration of diabetes in the younger group was 3.0 years and in the older group 4.2. The children had 3 main meals and 3.4 light meals daily. The median daily number of sandwiches was 7, often offered as snacks. All children used a low-fat margarine, low-fat cheese and low-fat milk. Sweets and diabetic food were seldom used. Of the energy intake protein contributed 18 per cent, fat 32 per cent and carbohydrates 50 per cent, including sucrose 2 per cent. Mean daily intake of fibre was 20 g. Compared to healthy children of the same age and from the same areas of Sweden the diabetics had a more regular meal pattern, their energy intakes did not differ, but the diet of diabetics was lower in fat and sucrose and higher in protein. The mean height, weight and BMI did not differ from healthy children.

Adolescent↗
PubMed1988

Intrathecal noradrenaline restores 5-methoxy-N,N-dimethyltryptamine induced antinociception abolished by intrathecal 6-hydroxydopamine.

Intrathecal administration of 6-hydroxydopamine (6-OHDA) abolished the antinociceptive effects of acute administration of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 1 mg/kg, s.c.) in the hot-plate, tail-flick and shock titration tests of nociception. The antinociceptive effects of 5-MeODMT, abolished by the prior intrathecal 6-OHDA treatment, were restored by intrathecal administration (2 or 1 microgram) of noradrenaline (NA), immediately prior to 5-MeODMT, in all three tests of nociception. Biochemical analysis confirmed severe NA depletions (95 percent loss) in the lumbar and thoracic regions of the spinal and much lesser dopamine depletions (25-35 percent loss). Intrathecal 5,7-dihydroxytryptamine (5,7-DHT) attenuated 5-MeODMT induced antinociception in the tail-flick test and combined NA + 5-MeODMT induced antinociception in the hot-plate and tail-flick tests. Intrathecal administration of 5,7-DHT caused a severe depletion of 5-hydroxytryptamine in the lumbar region of the spinal cord. The present findings demonstrate further the modulatory role of NA upon serotonergic systems in nociception and indicate the necessity of NA availability for induction of 5-MeODMT analgesia.

5,7-Dihydroxytryptamine↗
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

Acute electrophysiological and neurochemical effects of administration of MPTP in mice.

The changes occurring during the first few hours after subcutaneous administration of the catecholaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were investigated. Injections of MPTP (30-60 mg/kg s.c.) reduced the impulse rate by 12-45% in all dopaminergic neurones tested in the pars compacta of the substantia nigra. Depressions were maximal at 11 min and remained present for more than 2 hr after injection. This effect was completely abolished by prior administration of the catecholamine uptake inhibitor, nomifensine (13-69 mg/kg s.c.), which prevents the toxic metabolite of MPTP 1-methyl-4-phenylpyridine (MPP+) from entering dopaminergic neurones. These results suggest an intraneuronal mechanism underlying the observed depressions in impulse rate. Levels of dopamine (DA) were decreased at 3 hr after administration of MPTP (50 mg/kg s.c.) by 60% and 54% in the striatum and substantia nigra, respectively. Pretreatment with nomifensine (25 mg/kg, intraperitoneally) prevented the decrease in DA only in the striatum. This suggests an acute DA-releasing effect of MPTP in the striatum, mediated by intracellular accumulation of MPP+, while not explaining the depression of activity of DA neurones occurring with a different time course.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
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↗
PubMed1988

Noradrenergic and serotonergic involvement in brief shock-induced analgesia in rats.

Four experiments were performed to investigate the effects of different techniques causing noradrenergic and serotonergic depletions in the brain and spinal cord on brief shock-induced analgesia. Newborn pups were administered N-2-choloroethyl-N-ethyl-2-bromobenzylamine systemically (2 x 50 mg/kg, ip) and 6-hydroxydopamine administered either systemically (100 micrograms/g, sc) or directly (8 micrograms in 1 microliter, bilaterally) into the locus coeruleus region, or intrathecally (20 micrograms in 10 microliter) into the lumbar subarachnoidal space, caused notable and consistent attenuations of the analgesia caused by brief shock. These treatments reduced noradrenaline concentrations in the spinal cord drastically. A potentiation of brief shock-induced analgesia was caused by the administration of p-chlorophenyl-alanine, whereas administration of 5,7-dihydroxytryptamine, into the nucleus raphe magnus or intrathecally into the subarachnoidal space, produced attenuation of the analgesic effect. Biochemical analyses revealed marked 5-hydroxytryptamine depletions in the spinal cord. The present findings are discussed with regard to the role of spinal noradrenaline and 5-hydroxytryptamine involvement in brief shock-induced analgesia and in reactions to stressful events.

Animals↗
PubMed1988

Prenatal methylazoxymethanol treatment potentiates d-amphetamine- and methylphenidate-induced motor activity in male and female rats.

The effects of the stimulant drugs, d-amphetamine and methylphenidate, upon the motor activity of male and female off-spring of pregnant rats, treated on gestation day 15 with the antimitotic agent methylazoxymethanol (MAM, 25 mg/kg) were studied in four experiments. Cortical and striatal hypoplasia induced by prenatal administration of MAM resulted in increased concentrations of catecholamines in those regions. Administration of d-amphetamine and methylphenidate caused significant increases in motor activity; this effect was markedly potentiated in the MAM-treated rats, both the male and female off-spring. Thus, the locomotion and total activity parameters showed similar, but not identical, drastic increases in behaviour induced by the stimulant drugs as a result of the prenatal MAM treatment whereas for the rearing parameter a lesser potentiation by the MAM treatment was observed. This potentiation of the excitatory effects of the stimulant compounds upon the behavioural parameters is interpreted in terms of a relative increase in the density of catecholaminergic terminals in the forebrain regions of the central nervous system. The present results are discussed with regard to the utility of prenatal MAM treatment as a possible animal model for certain neurological disorders.

Animals↗
PubMed1987

Determination of monoamines by use of liquid chromatography with electrochemical detection in the study of selective monoamine neurotoxins.

Determination of regional monoamine levels in the CNS in the study of the effects of selective monoaminergic neurotoxins is a reliable method with which to study the morphological changes in denervated as well as re- or hyperinnervated regions as evidenced by comparisons with several other methods. In the acute stage, the changes in monoamine levels reflect both the beginning of the degeneration and the acute pharmacological effects exerted by several monoaminergic neurotoxins. The only exception to this seems to be the MPTP-induced chronic decrease of DA in the nucleus accumbens and the tuberculum olfactorium where no morphologic changes have been found so far.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Studies on the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in C57BL/6 mice. Comparison with three other strains of mice.

The effect of the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in C57BL/6 mice has been studied employing neuro- and histochemical techniques. The number of dopamine (DA) cell bodies in substantia nigra pars compacta (SNC) was reduced by 70% in MPTP-treated C57BL/6 mice, as demonstrated both by tyrosine hydroxylase (TH) immunohistochemistry and conventional histology (Cresyl violet staining) and an almost complete loss of DA fibers in striatum was also found. A detailed analysis of the effects of MPTP on endogenous catecholamine levels in various brain regions revealed that MPTP caused a severe reduction of endogenous DA in substantia nigra and striatum (35 and 5% of control) which was accompanied by an increase in the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratio. There was also a decrease of DA in nucleus accumbens and the olfactory tubercle to 41 and 44% of control, respectively, without any significant change in the DOPAC/DA ratio and density of TH-positive fibers. Small but significant decreases of the noradrenaline (NA) levels in septum, entorhinal cortex and frontal cortex were seen, although the uptake of [3H]NA in frontal cortex was not significantly changed. Minor MPTP-induced decreases of the serotonin levels in frontal cortex, occipital cortex and spinal cord were also seen. The MPTP treatment also induced a 55% increase of adrenaline levels in hypothalamus, while no changes were seen in pons-medulla and spinal cord. Comparing this with 3 other strains of mice, the MPTP-induced reduction of endogenous DA in striatum was most pronounced in C57BL/6, less in N.M.R.I. and CBA/Ca mice, and least in Swiss-Webster. Concerning the effect of MPTP on cortical NA levels, the same relation was at hand except for C57BL/6, where, as mentioned, the effect was merely detectable. No reduction of DA perikarya in SNC was seen in Swiss-Webster mice. These findings show that in mice major differences exist in sensitivity of catecholamine neurons to MPTP between different strains. The data show that MPTP can produce an almost complete, permanent and relatively selective degeneration of the nigrostriatal DA neurons in C57BL/6 mice similar to that seen in primates. This strain may therefore serve as a useful model for studies on various aspects of MPTP-induced parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

5-Hydroxytryptophol and 5-hydroxyindoleacetic acid levels in rat brain: effects of various drugs affecting serotonergic transmitter mechanisms.

The effect of various pharmacological treatments on the levels of free and total 5-hydroxytryptophol (5-HTOL) and 5-hydroxyindoleacetic acid (5-HIAA) in rat brain were investigated using a gas chromatographic-mass spectrometric technique. The disappearance of 5-HTOL following monoamine oxidase (MAO) inhibition induced by pargyline was more rapid (t1/2 10-15 min) than that of 5-HIAA (t1/2 30-40 min) in all regions investigated, indicating a rapid turnover of 5-HTOL. The selective MAO-A inhibitor chlorgyline produced a more pronounced reduction of 5-HTOL than of 5-HIAA, while the MAO-B inhibitor deprenyl was without effect on both serotonin metabolites. The MAO-A inhibitor amiflamine which is selective for serotonin neurons, was also more effective in reducing free 5-HTOL levels than of 5-HIAA levels, suggesting that the formation of 5-HTOL is closely associated with serotonin neurons. Neonatal treatment with the serotonin neurotoxin 5, 7-dihydroxytryptamine (5,7-HT) led to a more pronounced reduction of 5-HTOL levels in cerebral cortex than that of 5-HIAA levels, while the increase of 5-HTOL levels in pons-medulla was more marked than of 5-HIAA levels. Probenecid treatment increased several fold both conjugated 5-HTOL and 5-HIAA levels in brain tissue. An increase was also noted for free 5-HTOL, although of less magnitude. Treatment with the serotonin receptor active agents methiothepin and d-lysergic acid diethylamide produced similar alterations of free 5-HTOL and 5-HIAA. The present results have demonstrated that free 5-HTOL has a rapid turnover in rat brain and that free 5-HTOL levels may serve as a useful index for serotonin turnover.

Animals↗