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Biomedical subjects

S Wolfarth

Publications and source records attributed to S Wolfarth.

72 records · Page 4Linked to original sources
PubMed1977

Effects of intrastriatal injections of atropine and methacholine on the apomorphine-induced gnawing in the rabbit.

To find out the anatomical location of the target point of cholinergic-dopaminergic equilibrium, atropine (40 microng) or methacholine (10 microng) were injected through previously implanted cannulas into various places of caudate nucleus and putamen of the rabbit, and the effect of the injections on stereotype gnawing induced by subcutaneously or intravenously administered apomorphine (1--2 mg/kg) was assessed. The intensity of gnawing was measured using a special apparatus, counting each bite. Atropine inhibited the stereotype, while metacholine potentiated it. The effects were evident with the method used, but difficult to reveal with the classical method of assessing the intensity of stereotyped behavior, based on visual observation. The results suggest that the striatum is not a target point for the cholinergic component of the cholinergic-dopaminergic equilibrium in the central nervous system.

Animals↗
PubMedDate not supplied

Influence of long-lasting administration of neuroleptics on cortical NMDA receptors and phencyclidine-induced deficit in the sensorimotor gating in rats.

The aim of this study was to examine the role of cortical NMDA receptors in the antipsychotic action of neuroleptics. Haloperidol (1 mg/kg/day) and clozapine (30 mg/kg/day) were administered to rats in drinking water. Autoradiographic and saturation binding analyses showed that a 3-month treatment with both haloperidol and clozapine increased the density of NMDA receptors labelled with [3H]CGP 39653 (a competitive antagonist) in the parietal and insular cortices. Haloperidol additionally increased the binding of that ligand in the frontal cortex. None of those neuroleptics influenced the binding of [3H]MK-801, an uncompetitive antagonist of NMDA receptors, in the frontal, parietal or insular cortices. A 6-week and a 3-month treatment with haloperidol antagonized the deficit of prepulse inhibition induced by phencyclidine (5 mg/kg s.c.). In contrast, short-term (4-day) administration of that neuroleptic was ineffective. The present study suggests that the increased density of cortical NMDA receptors, induced by long-term neuroleptic administration, may overcome the deficit of sensorimotor gating induced by phencyclidine. However, contribution of such an effect to the antipsychotic activity needs to be established.

Animals↗
PubMedDate not supplied

On the choice of so-called placebo solution for the intranigral microinjection in the rat.

Rats moving freely in their cages were injected into substantia nigra with bidistilled water, with NaCl solutions of various concentrations or with a multionic Merle's solution. The solutions were administered uni- or bilaterally at volumes of 1-5 mul through chronically implanted chemitrodes. The behavior of animals and the EEG of frontal cortex, hippocampus, caudate nucleus and substantia nigra were observed. A part of the usual EEG record analysis two channels of EEG were evaluated with amplitude integrators. The main goal of the experiment was to find the optimal solvent for microinjection into the substantia nigra. So-called physiological saline solution (0-9% NaCl) was found to be most toxic and the multionic Merle's solution most suitable among the control fluids tested. The influence of "pressing effect", of pH as well as the influence of ionic concentrations of solutions tested are discussed.

Animals↗
PubMedDate not supplied

The participation of the nigro-thalamic pathway in the nigral control of the caudate nucleus.

Unilateral injections of carbachol (CCh, 2 mul) to lateral parts of substantia nigra (SNlat) of the rabbit increased the alert index (participation of alert pattern in EEG), produced epileptoidal EEG discharges, sniffing, ipsi- and contralateral rotations, and abnormal movements of fore limbs, which may be regarded as an equivalent of localized seizures. Ipsilateral rotations appeared together with epileptoidal discharges confined to SNlat, while contralateral -- with discharges in ventrolateral thalamic nucleus (VLTh). The EEG discharges appeared firstly and had the longest duration in VLTh. Injection of CCh to medial substantia nigra (SNmed) did not produce contralateral turnings and rotations, and epileptoidal EEG discharges appeared primarily in SNmed. In rabbits with previously lesioned nigro-neostriatal pathway (NSP) at the level of Forel's fields, the EEG discharges produced by CCh injected into SNlat appeared firstly and were most prolonged in SNlat, while they appeared much later in caudate nucleus (NC), cerebral cortex, and VLTh. The contralateral rotations were inhibited, and ipsilateral ones -- potentiated in the lesioned rabbits.

Animals↗
PubMedDate not supplied

Contralateral rotations induced by intrastriatal injections of agonists of excitatory amino acid receptors.

NMDA (100, 250 and 500 ng/0.5 microliters), kainic acid (50 and 100 ng/0.5 microliters) and AMPA (500 and 1000 ng/0.5 microliters), injected unilaterally into the ventrolateral part of the intermediate region of the caudate-putamen of rats, induced contralateral rotations. It is proposed that stimulation of NMDA, kainate and AMPA receptors present on strionigral neurons evokes an "antiparkinsonian effect".

Animals↗
PubMedDate not supplied

Muscle rigidity induced by the opioid analgesic tramadol, but not by the non-opioid flupirtine.

The influence of high doses of two analgesic drugs, tramadol and flupirtine on the electromyographic activity in the gastrocnemius soleus muscles was examined. Tramadol (100-200 mg/kg po) dose-dependently induced a tonic electromyographic activity, which is generally accepted as a model of the opiate-induced muscle rigidity. That effect was antagonized by intraperitoneal injection of naloxone (0.8 mg/kg ip). On the other hand, flupirtine even in the high doses (100-200 mg/kg po) did not induce any tonic electromyographic activity. The obtained results confirm an opiate-like action of tramadol, but not that of flupirtine, on the muscle tension.

Administration, Oral↗
PubMedDate not supplied

Specific involvement of striatal D1 and D2 dopamine receptors in the neuroleptic catalepsy in rats.

Since highly specific antagonists of D1 (SCH 39166) and D2 (raclopride) dopamine receptors have recently become available, we decided to investigate the role of striatal populations of these receptors in catalepsy - an animal model of neuroleptic-induced parkinsonism in humans. Injections of raclopride (2.5, 5 and 10 micrograms/0.5 microliters) into the ventro-rostral part of the striatum induced a strong, dose-dependent and long-lasting catalepsy. Intrastriatal injections of SCH 39166 (1.5 and 3.6 micrograms/ 0.5 microliters) also evoked a dose-dependent, but short-lasting catalepsy. The present results suggest, that neuroleptic side-effects are specifically dependent on the blockade of D2 and D1 dopamine receptors in the striatum.

Animals↗
PubMedDate not supplied

Lack of a strong influence of neuroleptic decanoates on dopaminergic and GABAergic functions.

Data concerning the incidence of extrapyramidal symptoms and the development of the supersensitivity to dopamine after administration of depot neuroleptics are controversial. The aim of the study was to examine the influence of depot neuroleptics on the sensitivity of dopamine receptors and GABA nigral receptors. Haloperidol decanoate (30 or 60 mg/kg im) and fluphenazine decanoate (12.5 or 25 mg/kg im) were injected twice at a 15 day interval. These treatments induced weak but very long-lasting catalepsy (60-105 days depending on the neuroleptic and its dose). The only significant enhancement of the apomorphine (0.25 mg/kg sc) stereotypy was observed 135 days after the lower dose of haloperidol and 230 days after the lower dose of fluphenazine. Haloperidol decanoate (30 mg/kg) did not influence the number of contralateral rotations induced by muscimol (10 or 25 ng/0.5 microliter) injected into the substantia nigra pars reticulata 35, 55 and 135 days after the first injection. Present results indicate that the dopaminergic supersensitivity after administration of depot neuroleptics is weak and appears very late, and that haloperidol decanoate does not induce nigral supersensitivity to GABA. It is suggested that the depot neuroleptics might induce less extrapyramidal symptoms in the clinic than the daily neuroleptic treatment.

Animals↗
PubMedDate not supplied

Dopamine receptors--the present state of research and perspectives.

The aim of the review is a brief description of the present status of research and perspectives in the field of multiple dopamine receptors, as well as of the importance of new discoveries for the treatment of schizophrenic psychoses and Parkinson's disease. Since the discovery of D1 and D2 dopamine receptors in the seventhies, evidence has accumulated for the existence of some new dopamine receptors. Among them the D3, D4 and D5 receptors, as well as their isoforms have been cloned. Molecular biology and pharmacology of these receptors have been exhaustively studied in recent years. These studies have prompted a number of hypotheses which open new perspectives for investigation into pathophysiology and therapy of schizophrenia and Parkinson's disease.

Antiparkinson Agents↗
PubMedDate not supplied

Age-related changes in glutamate receptors: an autoradiographic analysis.

The aim of the present study was to evaluate age-related changes in NMDA and AMPA receptors in old female rats. To this end a quantitative autoradiography of [3H]-MK-801 and [3H]-AMPA binding was performed in the brain of young (3-month-old), middle-aged (12-month-old) and old (36-month-old) rats. Moreover, the binding of [3H]-spiperone to D2 dopamine receptors was also examined. No changes were observed in the binding of [3H]-MK-801 or [3H]-AMPA in middle-aged rats compared to young ones. In the caudate-putamen and shell and core of the nucleus accumbens septi of old rats, a pronounced decrease in the [3H]-MK-801 binding and a decreasing tendency in the [3H]-AMPA binding were observed. Furthermore, the binding of [3H]-MK-801 and [3H]-AMPA was reduced in the hippocampal formation and, additionally, a marked decline in the [3H]-MK-801 binding in different parts of the cerebral cortex including the frontal, parietal, cingulate, pyriform and insular cortices was found. The [3H]-spiperone binding progressively decreased with age in the dorsolateral, ventrolateral and medial caudate-putamen. The present results show that aging processes lead to changes in the binding of both [3H]-MK-801 to NMDA and [3H]-AMPA to AMPA receptors in a number of structures, a phenomenon which may reflect motor and memory disturbances found in old rats and elderly humans.

Aging↗