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Biomedical subjects

G Jonsson

Publications and source records attributed to G Jonsson.

At least 55 records · Page 3Linked to original sources
PubMed1987

Effects of acute and chronic treatment with imipramine on 5-hydroxytryptamine nerve cell groups and on bulbospinal 5-hydroxytryptamine/substance P/thyrotropin releasing hormone immunoreactive neurons in the rat. A morphometric and microdensitometric analysis.

Groups of male rats were treated for a period of 14 days with imipramine (10 mumol/kg) given twice daily. Separate groups of rats received a single dose treatment using the same dose and experimental design as for the repeated treatment. Employing the avidin-biotin immunoperoxidase technique for immunohistochemistry 5-hydroxytryptamine (5-HT)-, substance P(SP)- and thyrotropin releasing hormone (TRH)-like immunoreactivities (IRs) were visualized in consecutive coronal sections of the brain stem and of the spinal cord. The IRs were studied by means of morphometric and microdensitometric procedures using automatic image analysis on profiles representing nerve terminal networks of the ventral horn of the cervical and lumbar enlargements of the spinal cord as well as their coexistence (5-HT/SP and 5-HT/TRH). With the same technique 5-HT IR was measured in the 5-HT nerve cell groups of the medulla oblongata (B1, B2, B3) and of the nucleus raphe dorsalis (B7) of the midbrain. In addition 5-HT and 5-hydroxyindolacetic acid (5-HIAA) levels were measured in the ventral and dorsal horns of the cervical and lumbar enlargements of the spinal cord using high performance liquid chromatography (HPLC). In the same parts of the spinal cord SP IR was studied by means of radioimmunoassay (RIA). The microdensitometric studies showed that chronic, but not acute, imipramine treatment selectively increased SP IR in the 5-HT/SP/TRH costoring nerve terminals of the medial part of the ventral horn in both the cervical and the lumbar enlargements. Furthermore, quantitative analysis of the entity of coexistence in the 5-HT nerve terminals networks of these areas showed that all the 5-HT nerve terminals contained SP and TRH IRs and that this phenomenon remained after acute and chronic imipramine treatment. The microdensitometric studies on the 5-HT nerve cell groups of the medulla oblongata and of the nucleus raphe dorsalis demonstrated that chronic, but not acute, imipramine treatment selectively increased 5-HT IR in the nerve cell bodies of the lateral part of group B3 as evaluated from the median grey values. Acute, but not chronic, imipramine treatment significantly increased the field area of 5-HT IR of nerve cell bodies in group B7, reflecting an increase in the mean profile area of the 5-HT IR nerve cell body profiles. Instead, the mean profile area of 5-HT IR cell bodies of group B1 was acutely reduced by imipramine.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

(+)-8-OH-DPAT and 5-MeODMT induced analgesia is antagonised by noradrenaline depletion.

In experiments with both rats and mice the 5-HT agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-N,N-dimethyl-tryptamine (5-MeODMT) were shown to produce reliable analgesic effects after acute administration (1 mg/kg SC) in the tail-flick, hot-plate and shock-titration tests of nociception. Prior treatment with the noradrenaline neurotoxin, N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4), systemically administered to both rats and mice abolished the analgesic effects of both the 5-HT agonist compounds in all the tests of nociception used. Intrathecal 6-hydroxydopamine (6-OHDA) treatment also abolished the analgesic effects of 8-OH-DPAT and 5-MeODMT; in the tail-flick test the analgesia induced by 8-OH-DPAT was reversed to an hyperalgesia. Biochemical analyses confirmed notable noradrenaline depletions in the spinal cord. It is concluded that an important interaction between presynaptic noradrenergic terminals and serotonergic receptor sites, possibly 5-HT1A, mediates spinal nociception processes.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1987

Norepinephrinergic reinnervation of cat occipital cortex following localized lesions with 6-hydroxydopamine.

We studied biochemical and morphological changes in central catecholamine (CA) terminals in the kitten visual cortex following direct infusion with 4 mM 6-hydroxydopamine (6-OHDA) for a week. Two zones may be distinguished within the cortical area affected by 6-OHDA (a radius of approximately 10 mm). In the primary lesion zone (a radius of approximately 5 mm) near the center of the 6-OHDA infusion, excluding an area of non-specific damage left by cannulation (a radius of less than 1.5 mm), we found: (1) absence of fluorescent CA terminals by histochemistry; (2) very low desipramine-sensitive uptake of tritiated norepinephrine (NE) by cortical slices (desipramine-resistant NE uptake stayed high); (3) a 50% increase in beta-adrenoreceptor binding sites by densitometry of light microscopic autoradiograms; and (4) low levels (less than 20% of control) of endogenous NE and low to moderate levels (10-70%) of endogenous dopamine (DA). In the surrounding zone (about 5-10 mm from the infusion center), however, none of the above changes were observed, except for a moderate to substantial reduction (50-80% of control) in endogenous NE and a small (10-20%) reduction in endogenous DA. Within two weeks after the end of the cortical 6-OHDA infusion, the dimensions of the cortical area devoid of CA terminals became substantially smaller than those found earlier. Fluorescent CA terminals were seen virtually everywhere in the cortex by 4 weeks, including the scar left by placement of the infusion cannula. In 24 weeks CA terminals in the occipital cortex appeared close to normal in density as well as in fluorescence intensity. Biochemical assays also revealed the recovery trend of CA contents. A steady increase in the NE content was obtained in the surrounding zone, with the stronger trend at its periphery, eventually attaining full recovery in 23 weeks. The recovery was slow in the primary lesion zone, especially near the infusion center, though there was a continual increase in endogenous DA toward control even at the infusion center.

Animals↗
PubMed1987

Sprouting of striatal serotonin nerve terminals following selective lesions of nigro-striatal dopamine neurons in neonatal rat.

The effects of neonatal intracisternal 6-hydroxydopamine (6-OHDA; 50 micrograms) treatment on striatal serotonin (5-HT) nerve terminals in rat have been characterized using histo- and neurochemical methods. The 6-OHDA lesion caused a 60% reduction of striatal dopamine (DA) concentration when analyzed in the adult stage, while 5-HT levels were increased by about 40% and 3H-5-HT uptake in vitro was increased by about 60%. Using computerized image analysis, a marked increase in 5-HT-like immunoreactive terminal density was found in both rostral (+200%) and caudal (+50%) striatum. Pretreatment with the DA uptake blocker amfolenic acid completely counteracted the 6-OHDA-induced alterations in both DA and 5-HT neurons in the striatum, while pretreatment with the noradrenaline uptake blocker desipramine had no significant effects. Regional analysis of 5-HT levels in the CNS after neonatal 6-OHDA treatment or the combined desipramine + 6-OHDA treatment showed no significant effect in any of the brain areas analyzed, apart from the observed 5-HT increase in striatum. It was furthermore observed that the striatal 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio was decreased, while the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratio was increased following the 6-OHDA lesion, indicating compensatory mechanisms in turnover of transmitters. These alterations were completely reversed after pretreatment with amfolenic acid. The present results support the view that the 5-HT hyperinnervation following neonatal 6-OHDA treatment is a collateral sprouting response induced by lesioning of the striatal DA neurons.

Animals↗
PubMed1986

Selective lesioning of forebrain noradrenaline neurons at birth abolishes the improved maze learning performance induced by rearing in complex environment.

The effect of selective destruction of forebrain noradrenaline (NA) neurons induced by 6-hydroxydopamine (6-OHDA) at Day 1 after birth on Hebb-Williams maze performance was investigated in adult rats housed after weaning in a complex environment (EC) or an isolated (IC) environment for 35 days. Saline treated control rats raised in the EC made fewer errors than those raised in the IC. This effect of EC was completely abolished in 6-OHDA treated rats; for these animals no improved performance due to the housing condition was obtained. Protection of the NA neurons against 6-OHDA neurotoxicity by pretreatment with desipramine (DMI) resulted in an effect of EC identical to that seen in saline-treated controls. Postweaning housing in the IC led to an increased locomotion as compared to housing in EC, but this effect was not affected by neonatal 6-OHDA and/or DMI treatment. Neurochemical analysis confirmed cortical NA and metabolite depletion as well as a good protection by the DMI pretreatment. The present results indicate that central NA neurons are involved critically in mediating mainly the cognitive components of behavioral alterations induced by EC.

Animals↗
PubMed1986

Uptake inhibition protects nigro-striatal dopamine neurons from the neurotoxicity of 1-methyl-4-phenylpyridine (MPP+) in mice.

Intracerebroventricular administration of MPP+ to C57 BL/6 mice caused a pronounced depletion of striatal levels of dopamine and 3,4-dihydroxyphenyl-acetic acid ipsilaterally, and a less marked depletion contralaterally. The MPP+-induced reductions were clearly diminished by pretreatment with the dopamine uptake inhibitors mazindol and nomifensine. Similar results were obtained from determinations using tyrosine hydroxylase immunohistochemistry. These results are consistent with the hypothesis that MPTP neurotoxicity is related to the formation of MPP+ from MPTP outside the dopamine neurons and that subsequent uptake of MPP+ into these neurons initiates degeneration.

1-Methyl-4-phenylpyridinium↗
PubMed1986

Noradrenaline-serotonin interactions in the control of sexual behavior in the male rat: DSP4-induced noradrenaline depletion antagonizes the facilitatory effect of serotonin receptor agonists, 5-MeODMT and lisuride.

The present communication reports how depletion of central noradrenaline neurons of DSP4 treatment antagonizes the facilitatory actions of 5-MeODMT and lisuride on male rat sexual behavior. In males with intact noradrenaline, 5-MeODMT facilitated sexual behavior by reducing the number of intromissions required for ejaculation; inhibitory actions were also noted, since 5-MeODMT prolonged intromission and ejaculation latencies. In DSP4-pretreated animals the inhibitory effect of 5-MeODMT remained unchanged, whereas its facilitatory action was abolished. Consistent with previous research, lisuride also reduced intromission frequency prior to ejaculation. This facilitation of sexual behavior was not observed in DSP4-treated animals. In the male rat, ejaculations following the first have a lower latency and are preceded by a lower number of intromissions. This naturally occurring facilitation of sexual behavior was not prevented by DSP4-induced noradrenaline depletion. Our results suggest that serotonin and noradrenaline interact in the control of sexual behavior in the male rat.

Animals↗
PubMed1986

Differential time course of protection by monoamine oxidase inhibition and uptake inhibition against MPTP neurotoxicity on central catecholamine neurons in mice.

Pretreatment with the monoamine oxidase inhibitor pargyline or the catecholamine uptake blocker nomifensine both protected central catecholamine neurons against MPTP-induced neurotoxicity as monitored by analyzing catecholamine levels and [3H]mazindol binding. Post-treatment with the inhibitors showed that the administration of nomifensine could be delayed longer than that of pargyline in order to achieve a protective effect. The results are compatible with the view that the monoamine oxidase-catalyzed conversion of MPTP to a toxic metabolite MPP+ occurs mainly extraneuronally. MPP+ is subsequently taken up and accumulated selectively in catecholamine neurons, initiating degeneration.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Spinal noradrenergic neurotransmission and the analgesia induced by brief footshock.

Antinociception induced by brief footshock as well as by 5-methoxy-N,N-dimethyltryptamine was antagonized by lesions of the descending bulbospinal noradrenergic (NA) pathways by intrathecal injections of 6-hydroxydopamine. The alpha 2-adrenoceptor antagonist, yohimbine, injected intrathecally also blocked both types of nociceptive effects in the tail-flick and hot-plate tests. 5-Methoxy-N,N-dimethyltryptamine (1 mg/kg) potentiated shock-induced antinociception and this potentiation was also antagonized by decreased NA neurotransmission. These findings suggest an important role for spinal NA innervation, and possibly alpha 2-adrenoceptors in antinociception induced by brief footshock and serotonergic receptor stimulation induced analgesia in rats.

Afferent Pathways↗
PubMed1986

Noradrenergic-serotonergic interactions and nociception in the rat.

Spinal noradrenaline (NA) depletion in rats, via either systemic N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4) or intrathecal 6-hydroxydopamine (6-OHDA), reversed and/or abolished the analgesic effects of the 5-hydroxytryptamine (5-HT) agonists, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and p-chloroamphetamine (PCA), in shock titration, hot-plate and tail-flick measures of pain sensitivity. Spinal NA depletion also abolished the analgesic effects of 5-HT itself, administered intrathecally, in all three nociception tests and potentiated the analgesic effects of intrathecal NA, a demonstration of receptor supersensitivity. Spinal 5-HT depletion, via intrathecal 5,7-dihydroxytryptamine (5,7-DHT), only attenuated 5-MeODMT-induced analgesia in the tail-flick test but potentiated the 5-MeODMT effect in the hot-plate test. Intrathecal 5,7-DHT treatment caused a drastic potentiation of NA-induced analgesia in the shock titration and tail-flick tests but not in the hot-plate test. Biochemical analyses confirmed the NA and 5-HT depletion. The spinal noradrenergic system appears to be an important tonic factor modulating the function of the descending 5-hydroxytryptaminergic pathway.

5,7-Dihydroxytryptamine↗
PubMed1986

GM1 ganglioside counteracts selective neurotoxin-induced lesion of developing serotonin neurons in rat spinal cord.

The effect of exogenous monosialoganglioside GM1 on neurotoxin-induced lesioning of bulbo-spinal serotonergic neurons of newborn rats was studied by means of biochemical and immunocytochemical techniques. 5,7-dihydroxytryptamine (5,7-HT, a selective serotonin neurotoxin) treatment of newborn rats caused a pronounced reduction of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in the thoracic and lumbar spinal cord, while an increase of 5-HT and 5-HIAA was found in the pons medulla. These biochemical alterations were regionally correlated with similar changes in 5-HT nerve terminal density analyzed by image analysis. GM1 administration (30 mg/kg for 4 consecutive days) antagonized the reduction of 5-HT and 5-HIAA levels induced by 5,7-HT treatment in the lumbar spinal cord of 2-month-old rats, as well as the decrease of 5-HT nerve terminal density in both thoracic and lumbar spinal cord of 1- and 2-month-old rats. A minor counteracting effect of GM1 was found in the pons medulla where the neurotoxin induced an increase of 5-HT and 5-HIAA levels. These data support the hypothesis that GM1 may have a preventing action on retrograde degenerative processes following chemical lesion and/or a growth-stimulating effect on injured 5-HT neurons.

5,7-Dihydroxytryptamine↗
PubMed1986

The catecholamine uptake blocker nomifensine protects against MPTP-induced parkinsonism in monkeys.

Administration of MPTP (1-methyl-1,2,3,6-tetrahydropyridine) to Macaca fascicularis monkeys produced severe parkinsonism (hypokinesia, tremor, rigidity, aphagia, adipsia) and more than 90% loss of nigral dopamine neurons, striatal dopamine content and striatal 3H-mazindol binding. Treatment with the catecholamine uptake blocker nomifensine counteracted the behavioral, histological and neurochemical effects induced by MPTP. For obtaining best protection, nomifensine had to be administered for weeks after MPTP. The results suggest that the selective target-directed neurotoxic action of MPTP on dopamine neurons in monkeys is mediated via the dopamine uptake mechanism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Central noradrenaline depletion antagonizes aspects of d-amphetamine-induced hyperactivity in the rat.

The effects of noradrenaline (NA) depletion upon amphetamine-induced hyperactivity were examined in five experiments. Central NA depletion via either systemic DSP4 or neonatal 6-OHDA antagonised the amphetamine-induced (2 mg/kg SC) increase in rearing behaviour, whereas lesions of the dorsal noradrenergic bundle using 6-hydroxydopamine antagonised the increase in locomotor activity. Peripheral NA depletion following systemic 6-hydroxydopamine to adult rats did not cause any changes in motor activity after acute amphetamine administration. Desipramine, the selective NA uptake inhibitor, blocked the effects of DSP4 upon amphetamine-induced rearing. NA depletion antagonised hyperactivity produced by the 2 mg/kg dose of amphetamine, but not the hyperactivity (rearing or locomotion) effects of amphetamine at 1, 4 or 8 mg/kg.

Animals↗
PubMed1986

5-HT agonist induced analgesia modulated by central but not peripheral noradrenaline depletion in rats.

The antinociceptive effect elicited by the 5-hydroxytryptamine (5-HT) agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) was reversed or blocked in animals which had previously sustained severe spinal noradrenaline (NA) depletion via either systemic N-2-chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP 4), neonatal 6-hydroxydopamine (neon. 6-OHDA), or intrathecal 6-OHDA treatment. Biochemical analysis of the lumbar spinal cord samples confirmed severe central NA depletions. Animals were tested with nondamaging heat pain (tail-flick test, hot-plate test) and electric footshock titration to determine the amount of antinociception or nociception. Peripheral NA depletion following intravenous (i.v.) 6-OHDA injection to adult rats had no effect on the antinociception induced by 5-MeODMT, but did cause severe NA depletions in the left heart atrium. These results suggest a modulatory effect of central and not peripheral noradrenergic system upon 5-HT agonist induced analgesia, and also give evidence that this effect is spinally mediated.

5,7-Dihydroxytryptamine↗
PubMed1986

DSP4-induced noradrenergic lesions increase beta-adrenergic receptors and hippocampal electrophysiological responsiveness.

Following profound (greater than 90%) depletions of norepinephrine (NE) by the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), the numbers of beta-adrenergic receptors were significantly increased (20-25%) in rat hippocampal and somatosensory cortical membranes; however, the numbers of alpha 1-adrenergic receptors and the affinities of both types of receptors were unaffected. This selective up-regulation of beta-adrenergic receptors was evident 1 week after DSP4 administration and was maintained for at least 2 more weeks. In electrophysiological experiments in the hippocampal slice preparation, responses to threshold as well as maximal concentrations of isoproterenol were enhanced 150% and 33%, respectively, in the DSP4-lesioned animals. The results demonstrate that nearly complete depletion of brain NE produced by administration of DSP4, like that produced by 6-hydroxydopamine, results in increased numbers of beta- but not alpha-adrenergic receptors, and suggest that the density of the former are regulated by afferent noradrenergic fibers. Furthermore, the functional significance of the increased number of hippocampal beta-adrenergic receptors is directly manifested in a greater electrophysiological responsiveness to an exogenously administered beta-adrenergic receptor agonist.

Action Potentials↗
PubMed1986

Impaired selective attention in methylazoxymethanol-induced microencephalic rats.

Prenatal treatment of rats on gestation day 15 with methylazoxymethanol (MAM) caused forebrain microencephaly. Several behavioral tests were performed when the rats had reached an adult age. MAM treated rats were hyperactive, and were severely impaired in the acquisition of successive position reversal in a T-maze. The microencephalic rats failed also to demonstrate contextual control of latent inhibition (the stimulus preexposure effect) in taste-aversion conditioning. These results indicate that MAM treatment disrupts attentional processes and that this may account for the learning impairment.

Animals↗