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  • Parkinson's disease  (5)
  • Dopamine  (3)
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  • 1
    Digitale Medien
    Digitale Medien
    Intrastriatal injection of dl-2-amino-5-phosphonovaleric acid (AP-5) induces sniffing stereotypy that is antagonized by haloperidol and clozapine (1986)
    Springer
    Psychopharmacology 90 (1986), S. 123-130 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Glutamate ; Dopamine ; Stereotyped sniffing ; AP-5 ; Haloperidol ; Clozapine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract dl-2-amino-5-phosphonovaleric acid (AP-5), which blocks glutamatergic transmission at the NMDA-preferring receptor, was injected into the antero-dorsal striatum of rats. AP-5-induced behavioural changes were assessed i) using a stereotypy rating scale and ii) using an experimental chamber designed to quantify sniffing. In both behavioural situations it was shown that AP-5 (10 μg/0.5 μl) induced continuous intensive sniffing similar to that induced by small doses of systemically administered amphetamine or apomorphine. However, oral stereotypies were not induced by AP-5. Systemically injected clozapine (5 and 10 mg/kg SC) as well as haloperidol (0.1 mg/kg IP) antagonized AP-5-induced sniffing. These results show that besides dopamine receptors, NMDA receptors are involved in the control of sniffing. In behavioural terms, the effect of glutamate mediated by the NMDA receptor in the striatum is opposite to that of dopamine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00172883
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  • 2
    Digitale Medien
    Digitale Medien
    6-Hydroxydopamine lesion of the rat prefrontal cortex impairs motor initiation but not motor execution (1994)
    Springer
    Experimental brain research 99 (1994), S. 524-528 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Prefrontal cortex ; 6-Hydroxydopamine ; Dopamine ; Noradrenaline ; Reaction and movement times ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We examined the effects of bilateral 6-hydroxydopamine (6-OHDA) lesions of the medial prefrontal cortex (PFC) in rats on motor initiation and execution in a simple reaction time task. Reaction times (RT) and movement times (MT) were measured in trained rats on four preand postoperative days. Animals with 6-OHDA lesions were selectively impaired on motor initiation as measured by a significant increase in RT on each postoperative day. Motor execution was intact postoperatively, since MT was not altered. Neurochemical analysis revealed a significant depletion of prefrontal dopamine (DA) and noradrenaline (NA) in lesioned animals. It was concluded that DA and, to a lesser extent, NA in the rat PFC were involved in monitoring RT performance.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00228988
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  • 3
    Digitale Medien
    Digitale Medien
    Haloperidol- and apomorphine-induced changes in pup searching behaviour of house mice (1988)
    Springer
    Psychopharmacology 95 (1988), S. 271-275 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Dopamine ; Maternal behaviour ; Response-switching ; Apomorphine ; Haloperidol ; House mouse
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Maternal pup searching behaviour of lactating house mice treated with apomorphine, haloperidol or saline was examined on a running board with a central depression as a nest. Pup searching was elicited by artificial ultrasonic stimuli: a female moved out from the nest either towards a 50 kHz tone (key stimulus) which is adequate to activate species specific pup searching behaviour or towards a 20 kHz tone (neutral stimulus), thus showing her preference for one of these stimuli. Under apomorphine (0.00625; 0.0125; 0.025 mg/kg) the females preferred the key stimulus. Nevertheless apomorphine (0.00625–0.025 mg/kg) prolonged response latencies and shortened the duration of pup searching. At the highest dose (0.05 mg/kg), apomorphine induced stereotyped sniffing. Haloperidol (0.025; 0.05; 0.1 mg/kg) had opposite effects to apomorphine: it lowered the threshold for elicitation, shortened response latencies and prolonged the duration of pup searching. Females treated with haloperidol (0.025–0.1 mg/kg) did not prefer the key stimulus. Changes in response elicitation and in the performance of pup searching induced by apomorphine and haloperidol, respectively, were assumed to be due to i) a reduced and an increased responsiveness to external stimuli respectively, ii) an enhanced and a reduced tendency for response switching respectively, and iii) a preference for spontaneous behaviour in apomorphine-treated females, with an increased dependence on exteroceptive stimuli following haloperidol.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00174523
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  • 4
    Digitale Medien
    Digitale Medien
    Dopamine-glutamate interactions in the basal ganglia (1998)
    Springer
    Amino acids 14 (1998), S. 5-10 
    Details
    ISSN: 1438-2199
    Schlagwort(e): Basal ganglia loops ; Reward ; Sensitization ; NMDA receptor ; Parkinson's disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In an attempt to formulate a working hypothesis of basal-ganglia functions, arguments are considered suggesting that the basal ganglia are involved in a process of response selection i.e. in the facilitation of “wanted” and in the suppression of “unwanted” behaviour. The meso-accumbal dopamine-system is considered to mediate natural and drug-induced reward and sensitization. The meso-striatal dopamine-system seems to fulfill similar funcions: It may mediate reinforcement which strengthens a given behaviour when elicited subsequently, but which is not experienced as reward or hedonia. Glutamate as the transmitter of the corticofugal projections to the basal ganglia nuclei and of the subthalamic neurons is critically involved in basal ganglia funcions and dysfunctions; for example Parkinson's disease can be considered to be a secondary hyperglutamatergic disease. Additionally, glutamate is an essential factor in the plasticity response of the basal-ganglia. However, opposite to previous suggestions, the NMDA-receptor blocker MK-801 does not prevent psychostimulant- nor morphine-induced day to day increase (sensitization) of locomotion. Also the day to day increase of haloperidol-induced catalepsy was not prevented by MK-801.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01345235
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  • 5
    Digitale Medien
    Digitale Medien
    Anticataleptic potencies of glutamate-antagonists (1991)
    Springer
    Amino acids 1 (1991), S. 225-237 
    Details
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Catalepsy ; Movement initiation ; NMDA antagonists ; Glycine ; Parkinson's disease ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The anticataleptic effects of non-competitive and competitive NMDA antagonists as well as those of an agonist at the allosteric glycine binding site of the NMDA receptor were tested in the catalepsy model. Some of these drugs were further tested in a reaction time task demanding rapid locomotor initiation. The results show that the non-competitive NMDA antagonists dizocilpine and memantine as well as the competitive antagonists CGP 39551, CGP 37849 and CPPene antagonized dopamine D2 receptor mediated catalepsy induced by haloperidol. D-cycloserine, a partial glycine agonist per se had no effects, but it enhanced the anticataleptic effects of dizocilpine when coadministered. However, the effects of CGP 37849 were abolished. Dopamine D1 receptor mediated catalepsy induced by SCH 23390 was antagonized by dizocilpine, memantine, CPPene, but not by CGP 37849. In the reaction time task dizocilpine, memantine and CGP 37849 were tested for their anti-akinetic and anti-bradykinetic potencies. All these compounds improved haloperidolinduced slowing of reaction time. However, they acted differentially on haloperidol-induced slowing of movement execution and decreased initial acceleration. Thus, antagonists at the NMDA receptor may have a therapeutic potential in the treatment of Parkinson's disease. Their potency can be manipulated specifically at the glycine binding site.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00806920
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  • 6
    Digitale Medien
    Digitale Medien
    The role of NMDA receptors in the slow neuronal degeneration of Parkinson's disease (1998)
    Springer
    Amino acids 14 (1998), S. 17-23 
    Details
    ISSN: 1438-2199
    Schlagwort(e): NMDA receptors ; Excitotoxicity ; Chronic neuronal degeneration ; Nigrostriatal neurons ; Parkinson's disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Parkinson's disease is a disorder, in which neurons of various neuronal systems degenerate. Furthermore, in such degenerating neurons, the cytoskeleton seems to be affected. In this respect, Parkinson's disease resembles Alzheimer's disease. Since it has been shown, that elevated levels of intracellular calcium can disrupt the cytoskeleton and that the stimulation of glutamate (NMDA) receptors can cause high intracellular concentrations of calcium, it has been suggested, that the stimulation of glutamate receptors plays a role in the slow degeneration in Alzheimer's and Parkinson's disease. In case of the degeneration of the dopaminergic nigrostriatal system in Parkinson's disease, neurons that contain calcium binding protein appear to be less vulnerable than the neurons that lack it, suggesting that calcium binding protein might protect these neurons from degeneration by preventing that cytosolic calcium concentrations increase excessively. And, since there is in the nigrostriatal system a glutamatergic afferent pathway (the prefrontonigral projection) and since dopaminergic nigrostriatal neurons contain postsynaptic NMDA receptors, glutamatergic excitation may play a role in the degeneration of the nigrostriatal system in Parkinson's disease. If so, it may be possible to protect the neurodegeneration of these dopaminergic neurons by NMDA receptor antagonists.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01345237
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  • 7
    Digitale Medien
    Digitale Medien
    Glycine site antagonists abolish dopamine D 2 but not D 1 receptor mediated catalepsy in rats (1994)
    Springer
    Journal of neural transmission 95 (1994), S. 123-136 
    Details
    ISSN: 1435-1463
    Schlagwort(e): Glycine ; NMDA ; 7-chlorokynurenate ; (R)-HA-966 ; haloperidol ; SCH 23390 ; dopamine ; D 1, D 2, catalepsy ; Parkinson's disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Catalepsy—a state of postural immobility (akinesia) with muscular rigidity (rigor)—and reduced locomotion in animals are behavioral deficits showing similarities with symptoms of Parkinson's disease (PD). The effects of the glycine site antagonists 7-chlorokynurenate and (R)-HA-966 on haloperidol-(D2 antagonist) and SCH 23390-(D 1 antagonist) induced catalepsy and reduced locomotion are investigated in rats. Both antagonists dose-dependently counteract dopamine D 2 receptor mediated catalepsy but they have no influence on locomotion. Neither 7-chlorokynurenate nor (R)-HA-966 has any effect on dopamine D 1 receptor mediated catalepsy. This finding is surprising, since NMDA receptor antagonists counteract both, dopamine D 1 and D 2 receptor mediated catalepsy. D 1 and D 2 receptors are located on different populations of neurons. Thus, the present findings suggest that these different neuronal populations have different sensitivity for ligands binding at the glycine binding site of the NMDA receptor.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01276431
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  • 8
    Digitale Medien
    Digitale Medien
    6-Hydroxydopamine lesion of locus coeruleus and the antiparkinsonian potential of NMDA-receptor antagonists in rats (1997)
    Springer
    Journal of neural transmission 104 (1997), S. 363-377 
    Details
    ISSN: 1435-1463
    Schlagwort(e): Noradrenaline ; locus coeruleus ; 6-OHDA lesion ; NMDA receptor-antagonists ; L-DOPA ; Parkinson's disease ; open field ; locomotion ; exploration ; behavior ; rat ; HPLC
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Behavioral and neurochemical effects after bilateral 6-hydroxy-dopamine locus coeruleus- (LC) lesion were examined in rats and compared to sham-lesioned controls. Behavior after treatment with the antiakinetic drugs dizocilpine, amantadine, memantine or L-DOPA as well as joint treatment of these drugs with haloperidol were tested in an open field with holeboard and in an experimental chamber. Under saline spontaneous activity (open field with holeboard) and sniffing (experimental chamber) were reduced after lesion. Injection of the proparkinsonian drug haloperidol decreased sniffing in all rats but to a greater extent in LC-lesioned rats. In combination with haloperidol none of the tested drugs could completely compensate for the motor deficits induced by the lesion. Neurochemical data revealed a reduced content of noradrenaline in the prefrontal cortex and in the posterior striatum of LC-lesioned rats. These results indicate that loss of LC neurons intensifies parkinsonian symptoms induced by blockade of dopamine D2-receptors, and lowers the antiakinetic potential of dizocilpine, amantadine, memantine or L-DOPA.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01277657
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