Biomedical subjects

M Jähkel

Publications and source records attributed to M Jähkel.

At least 19 recordsLinked to original sources

PubMed2001

Behavioral and neurochemical effects of anpirtoline and citalopram in isolated and group housed mice.

Acute effects of serotonergic drugs acting via different mechanisms were investigated by a social interaction test and subsequent determination of serotonin and dopamine metabolisms in mice housed in groups or isolated for 6 weeks. A resident/intruder test was performed with anpirtoline (5-HT1B receptor agonist in rodents; 1 mg/kg), citalopram (SSRI; 0.5 mg/kg) and saline treatment before animals were decapitated and different brain regions were frozen for subsequent HPLC-analyses. Behavioral investigations indicated a strong increase of aggressive behavior after 6 weeks of isolation housing. Acute citalopram treatment did not influence behavioral parameters of isolated and group housed mice. In contrast, anpirtoline antagonized isolation induced aggressive behavioral components in a specific manner. Analysis of dopamine and serotonin metabolism revealed that citalopram treatment did not affect dopamine metabolism, but reduced serotonin metabolism in the striatum, hippocampus, cortex and midbrain independent of housing conditions. In contrast, anpirtoline treatment increased dopamine metabolism in cortex, striatum and midbrain as well as influenced serotonin metabolism in a structure- and state-specific manner. Whereas anpirtoline decreased serotonin metabolism in the cortex, the midbrain and the hippocampus independent of housing conditions, in the striatum anpirtoline abolished the isolation induced decrease of serotonin metabolism. These results indicate that anpirtoline might induce antiaggressive effects via postsynaptic receptor- and structure-specific activation of serotonergic but also dopaminergic processes, whereas structure independent increase of synaptic serotonin via citalopram was ineffective to reverse aggressivity in isolated mice.

Aggression↗

PubMed2000

Open field locomotion and neurotransmission in mice evaluated by principal component factor analysis-effects of housing condition, individual activity disposition and psychotropic drugs.

Effects of housing condition and individual disposition on dopaminergically and GABAergically influenced open field locomotion and neurochemistry were studied in mice. Mice characterized as high active (HAM) and low active (LAM) by a running-wheel test were housed in groups or isolated for 1 day, 1 week, 3, 6, 12 or 18 weeks before an open field test was performed with saline, apomorphine (0.75 mg/kg) or diazepam (1.00 mg/kg) administration. Immediately afterwards animals were decapitated and brain sections were frozen for subsequent HPLC-analysis of dopaminergic and serotonergic transmitter metabolism. Principal component factor analysis (PCA) of locomotion variables provided three factors explaining 78.5% of total variance. Variables related to the amount of locomotion loaded highly on Factor 1 (F1-Activity), variables related to place utilization loaded highly on Factor 2 (F2-Exploration) and variables related to immobility and place preference loaded highly on Factor 3 (F3-Irritation). Apomorphine decreased F1-Activity with smaller effects in HAM and without changes in F2-Exploration and F3-Irritation independent on housing conditions. Diazepam exerted a decrease in F2-Exploration with a small increase in FI-Activity and no effects in F3-Irritation. Diazepam induced changes depended on housing conditions and were especially pronounced in isolated HAM. PCA of considerable locomotion and neurochemical data revealed interrelationships between striatal dopamine metabolism and F1-Activity, between cortical dopamine and serotonin metabolism and F2-Exploration as well as between cerebellar, hippocampal and striatal serotonin metabolism and F3-Irritation. The authors concluded that the application of PCA is a useful method to provide functionally relevant characteristics of behaviors and functionally relevant descriptions of interrrelationships between behavior and appropriate central nervous mechanisms. Furthermore the received behavioral characteristics (F1, F2, F3) of open field locomotion were sensitive to reveal housing and drug effects.

Animals↗

PubMed1998

Dynamic alterations of serotonergic metabolism and receptors during social isolation of low- and high-active mice.

Alterations induced by social isolation (1 day to 18 weeks) in low- and high-active mice (LAM and HAM) were studied in respect to serotonin metabolism, [3H]-8-OH-DPAT binding of presynaptic (midbrain), postsynaptic (hippocampus) 5-HT1A receptors and [3H]-ketanserin binding of cortical 5-HT2A receptors. Individual housing of mice was associated with reduction of serotonin metabolism, depending on isolation time and brain structure. Whereas a transient decrease in the striatum and cortex was detected between 1 week and 6 weeks, reduction of cerebellar and hippocampal serotonin metabolism was found later (12-18 weeks). Serotonergic systems of HAM were found to be more reactive to environmental disturbances, and their serotonin metabolism was more affected by social isolation. Isolation-induced upregulation of cortical 5-HT2A receptors was measured only in HAM. Densities of postsynaptic 5-HT1A receptors in the hippocampus did differ either in grouped or isolated mice. However, there were significant differences in hippocampal 5-HT1A receptor affinity, especially between 1 day and 3 weeks. Transient downregulation of presynaptic 5-HT1A receptors in the midbrain was found in isolated mice between 3 and 6 weeks. These results are discussed in terms of interactions between serotonergic alterations and isolation-induced aggression.

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

PubMed1998

Dopaminergic parameters during social isolation in low- and high-active mice.

Alterations induced by social isolation (1 day to 18 weeks) in low- and high-active mice (LAM and HAM) were studied in respect to locomotor activity, [3H]-spiperone binding in the striatum, striatal, and cortical dopamine metabolism, and presynaptic dopaminergic sensitivity to apomorphine (0.75 mg/kg; i.p.). Isolated HAM and LAM showed increased locomotor activity compared to group-housed mice after long-term isolation (6-18 weeks). Considering the studied dopaminergic parameters, it has been found that social isolation did not affect striatal D2 receptors, striatal and cortical dopamine metabolism, and apomorphine-mediated reduction of dopaminergic metabolism. The change of housing conditions was generally associated with an increase of cortical dopamine metabolism after 1 week. Activity type specific differences in group-housed LAM and HAM were found in the basal striatal dopamine metabolism and in the sensitivity of the nigrostriatal system to autoreceptor activation. The reduced striatal dopamine metabolism and the higher presynaptic sensitivity of HAM may be related to their high active running wheel behavior.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Influence of nootropic and antidepressive drugs on open field and running wheel behavior in spontaneously high and low active mice.

Mice differentiated by their running wheel activity into low and high active animals were chronically treated with the nootropics meclophenoxate, piracetam, vinpocetine, methylglucaminorotate, and the antidepressants lithium, desipramine, amitriptyline, and clomipramine. The influence of chronic drug treatment on running-wheel activity and open field locomotor behaviour was analyzed. Whereas with antidepressants rather sedative effects were observed in both activity types, the effects of nootropics were different in high and low active mice. Running-wheel scores increased in low active mice but decreased in high-active animals with an improvement in efficiency of locomotor behaviour in the open field of these mice after chronic nootropic treatment. In general, the effects of antidepressants seemed to be more uniform than those of the nootropics used.

Animals↗

PubMed1990

Effect of 2-mercapto-ethanol on some brain biochemical characteristics and behavioural changes in the ageing CBA/Ca mice.

Male CBA/Ca inbred mice were treated with a dose of 8 micrograms 2-mercapto-ethanol per animal per day in the drinking water from the age of 5 months onwards up to the age of 24 months. Dopamine release was greatly decreased in old animals in contrast to the elevation of dopamine release in the treated mice. Similarly, an elevated malondialdehyde content in brain homogenates was also observed in the aged treated animals compared with their controls. No essential differences were observed in locomotor activity and learning between treated an control mice.

Aging↗

PubMed1990

Effect of 2-mercaptoethanol on posthypoxic and age-related biochemical and behavioural changes in mice and rats.

2-Mercaptoethanol (2-ME) has a beneficial effect on the mean life span of laboratory rodents. This paper deals with the effects of 2-ME on changes of dopamine release from brain slices of old aged or hypoxia exposed mice and rats. The results were compared with data which reflect spontaneous peroxidation of brain lipid constituents. In addition, adequate behavioural properties were studied. Long-term 2-ME treatment for months abolishes the age-related decrease of transmitter release and prevents changes in malondialdehyde formation. If age-dependent release failure is already established, then neither single high doses of 2-ME nor repeated treatment for 3 weeks are effective. Posthypoxic release inhibition is prevented by a 2-ME pretreatment for 3 weeks but not by an acute single application even at high dosages. The preventive effect of 2-ME is a mediated one rather than an immediate direct action. Age-related behavioural deficits, such as locomotor activity, habituation performance and learning ability, do not reflect any effect of 2-ME long-term treatment.

Aging↗

PubMed1987

Neuronal transmitter sensitivity after social isolation in rats.

After 3 and 12 months of isolation rearing of rats, sensitivity of single neurons to microiontophoretically applied transmitters as well as neuronal spontaneous activity are analysed in striatum, cortex, hippocampus, locus coeruleus and nucleus raphis medialis. It is demonstrated that regulation of transmitter sensitivity, as well as spontaneous activity, depend on isolation duration, therefore showing time dynamics. Sensitivity changes of single neurons to distinct transmitters are not uniform and simultaneous in all areas but are structure specific. After 3 months of isolation an enhanced dopamine sensitivity is observed only in the striatum, whereas in the cortex the dopamine sensitivity is increased after 12 months isolation. A diminished response of single neuron activity to serotonin is demonstrable after 3 months of isolation in striatum and nucleus raphis. The observed changes are discussed in connection with biochemically and pharmacologically demonstrated changes in isolation. The complex patterns of neurobiological changes characterizing the isolation syndrome are emphasized.

Animals↗

PubMed1987

The influence of long-term treatment with haloperidol on neuronal activity and sensitivity in several brain structures of the rat.

The influence of long-term haloperidol pretreatment on neuronal spontaneous activity and transmitter sensitivity was investigated in prefrontal cortex, hippocampus and locus coeruleus. The changes are different in all areas as well as in the transmission systems involved. In particular cases, analogies exist between haloperidol- and isolation-induced changes, reflecting a comparable dopaminergic supersensitivity.

Action Potentials↗

PubMed1987

The influence of social isolation, hypoxia and immobilization on potassium-stimulated dopamine release from telencephalon slices of mice.

Dopamine release from mice telencephalon slices was investigated following immobilization or hypobaric hypoxia exposure during periods of social isolation of different length which itself affects dopamine release in a characteristic manner. Isolation initially results in a decreasing release, which is compensated at the end by adaptive processes. The decrease of dopamine release induced by immobilization is highly dependent on the foregoing isolation. On the other hand, a hypoxia-induced decrease of release always dominates the results. Adaptive processes in consequence of social isolation are supposed to be important in relation to immobilization effects but not to hypoxia-induced changes.

Adaptation, Physiological↗

PubMed1986

Altered neurobiological responses to acute immobilization in social-isolated mice.

Social isolation results in dynamic changes of neurobiological functions. The altered internal state of the CNS is reflected in changes in spontaneous behavior, changed responses to transmission-related substances and changed responsiveness to an additional impairment of normal relations between the organism and its environment. We analysed the influence of an acute 2-hour immobilization on such isolation-dependent changes. Whereas the susceptibility to pentetrazole-induced seizures increased continuously with lengthening of isolation and was not affected by the additional impairment, the responsiveness to transmission-related substances changed dynamically depending upon isolation-induced alterations. An immobilization-induced increase in responsiveness to LSD and propranolol was demonstrable in grouped controls and after short-term isolation. The apomorphine stimulation during prolonged isolation experienced a down- and an upregulation which were repeated in a stronger manner by immobilization responses especially after long-term isolation. It is suggested that the dynamics of isolation-induced changes coincided with changed acute adaptive functions.

Animals↗

PubMed1985

Posthypoxic transmitter release from brain slices and behavioural consequences of hypoxia in rats and mice.

Subsequent to a hypoxic exposure of adult rats and mice the stimulus induced release of dopamine from striatum slices is inhibited for several days. The posthypoxic release inhibition is not restricted to the striatal dopaminergic transmission system especially, but hypoxia causes comparable changes also in other brain regions regarding further transmitter systems. The transmitter release inhibition reflects a significant caudo-rostral gradient of increasing vulnerability of phylogenetically younger brain regions. The consequences of these biochemical changes in the brain following cessation of hypoxia are investigated with regard to behavioural manifestations. Corresponding in time with the inhibition of transmitter release and its restitution the seizure susceptibility is increased when pentetrazol is given in subconvulsive doses. On the other hand, the results of further tests (climbing behaviour, open field, rotarod test, forced-swimming test) do not point to behavioural changes induced particularly by a mild hypoxia.

Animals↗

PubMed1985

[Effect of lithium, carbamazepine, ca-valproate and diazepam on changes in social isolation-induced behavior in mice].

Neurobiological changes induced by social isolation of mice are used to characterize pharmacological influences of lithium and several other drugs. Lithium is able to prevent not only early serotoninergic changes but also enhanced aggressiveness and enhanced spontaneous locomotion, seen after long term isolation. Very similar to lithium are the effects of carbamazepine, whereas Ca-valproat and diazepam prevent the early serotoninergic (stress like) changes, but not later changes in aggressivity and locomotion.

Aggression↗

PubMed1985

[The dynamics of behavioral changes in mice induced by social isolation].

Various behavioural patterns such as spontaneous locomotion, open-field behaviour and aggressivity undergo typical changes in socially isolated mice. Each of them shows a specific course depending on the duration of isolation. Differences in time courses and quantitative changes demonstrate that not only a general mechanism such as decreased arousal threshold is responsible for the complex alterations. It seems that many different mechanisms in the CNS underly the isolation syndrome, but the functional connections between the different alterations are unknown.

Aggression↗

PubMed1984

Inhibition of isolation-induced changes in aminergic transmission by chronic lithium treatment.

Social isolation of mice leads to changes in aminergic transmission systems. After 6 weeks of isolation, an increase of apomorphine-stimulated climbing behavior is seen, reflecting an isolation-induced dopaminergic supersensitivity. After 1-3 weeks of isolation, a decrease of clonidine sedation is detectable, suggesting the development of noradrenergic alpha 2-receptor subsensitivity. The isolation-induced changes of both drug effects are prevented by lithium given over the time of isolation.

Animals↗

PubMed1984

[Development of tolerance to haloperidol in the rat striatum].

Microiontophoretic application of dopamine effects in the rat's striatum a dose-dependent inhibition of the glutamate-induced pulse activities. Acute systemic applications of haloperidol are able to abolish this dopamine-induced inhibition. After chronic pretreatment with haloperidol, however, acute administration of haloperidol can no longer antagonize the dopamine-induced inhibition of the pulse activity. Hence, it is likely that tolerance to haloperidol , as described in individual behavioral studies can develop also on the cellular level.

Animals↗

PubMed1983

[Effect of desipramine and social isolation on neuronal activity in rat hippocampus].

Chronic treatment of rats with desipramine leads to an increase of hippocampal neurons with low spontaneous activity. After an isolation rearing period of three months an increased spontaneous activity is seen in the hippocampus of rats. Furthermore the hippocampal spontaneous activity is related to age. Opposite alterations of spontaneous activity in desipramine treated and socially isolated rats, respectively, as well as their relations to noradrenergic transmission processes are discussed. The isolation syndrome as a model to test substances with antidepressive properties is also reviewed.

Animals↗

PubMed1980

[Modification of chemoreactive properties of neurons in the neocortex and hippocampus under the effect of electric stimulation of locus coeruleus].

Based on the findings of alterations in the chemoreactivity of neurons under conditioning and its possible significance for the formation of transient neuronal junctions, the authors investigated the influence of electrical stimulation of the Locus coeruleus upon the transmitter sensitivity of cortical and hippocampal neurons. The majority of neurons showed immediately after stimulation of the Locus coeruleus a different reaction to microiontophoretic application of acetylcholine, dopamine and glutamate than under normal conditions. Obviously there must have occurred qualitative changes because a superposition effect of the reactions following stimulation of the Locus coeruleus and application of the substances has rarely been observed. The release of noradrenaline provoked by the stimulation of the Locus coeruleus evidently leads to qualitative changes in the neurone texture, which may occur both inter- and intraneuronally.

Acetylcholine↗