Browsing by Author "Schmidt, Werner J."

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Open Access
6-Hydroxydopamine lesion of the rat prefrontal cortex impairs motor initiation but not motor execution
(1994) Hauber, Wolfgang; Bubser, Michael; Schmidt, Werner J.
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.
Open Access
Acquisition, but not retrieval of delayed alternation is impaired by ketamine
(1990) Hauber, Wolfgang; Schmidt, Werner J.
Dissociative anaesthetics as ketamine and related drugs induce marked behavioral changes in rats, in particular behavioral stereotypies and learning impairments. In the resent study the effect of ketamine on acquisition and retrieval of a delayed alternation task was investigated. Results indicate that ketamine (8mg/kg i.p.) impaired specifically acquisition, while retrieval was not affected. Thus, stereotypies competing with ongoing behavior and therefore interfere with learning, appear not to be causative to the acquisition deficit, since retrieval should be affected in the same way. A possible involvement of NMDA receptors in deficient acquisition is discussed.
Open Access
Anticataleptic potencies of glutamate antagonists
(1991) Schmidt, Werner J.; Zadow, Beate; Kretschmer, Beate D.; Hauber, Wolfgang
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
Open Access
Behavioural pharmacology of glutamate in the basal ganglia
(1992) Schmidt, Werner J.; Bubser, Michael; Hauber, Wolfgang
In Parkinson's disease the dopaminergic inhibition - mediated by DA2 receptors in the triatum - is reduced. Therefore glutamatergic excitation predominates in the antero-dorsal striatum. In turn the glutamatergic neurons of the subthalamic nucleus become disinhibited. Antagonists of the NMDAsubtype of glutamate receptor injected locally into the glutamatergically innervated nuclei or competitive and non-competitive NMDA-antagonista administered systemically, counteract parkinsonian symptom in animals.
Open Access
Differential effects of lesions of the dorsomedial and dorsolateral caudate putamen on reaction time performance in rats
(1994) Hauber, Wolfgang; Schmidt, Werner J.
In order to investigate the role of the dorsomedial and dorsolateral caudate-putamen (CPu) in movement initiation of rats, we examined the effects of quinolinic acid lesions (30 nmol in 1 μl) in these striatal subregions in a simple reaction time task. Results show that lesions of the dorsomedial, but not of the dorsolateral CPu increased reaction times. These findings provide further evidence for a functional heterogenity of the CPu and demonstrate an involvement of the dorsomedial CPu in processes related to rapid initiation of responses
Open Access
Discrete quinolinic acid lesions of the lateral but not of the medial caudate putamen reversed haloperidol-induced catalepsy in rats
(1993) Hauber, Wolfgang; Schmidt, Werner J.
Discrete lesions in the medial or lateral subregion of the rostral caudate-putamen (CP) were induced by bilateral intracerebral injections of a low dose of quinolinic acid (30 nmol in 1 mgrl/per side) in rats. Quinolinic acid lesions in the lateral CP potently reversed haloperidol-induced catalepsy (0.5 mg/ kg,i.p.), while lesions in the medial CP were not effective. Spontaneous locomotor activity was not altered significantly after quinolinic acid lesions of either the medial or lateral CP. These results show that the lateral CP seems to be important for the expression of neuroleptic-induced catalepsy and thus further corroborate the concept of a functional heterogenity of the striatum
Open Access
Effects of intrastriatal blockade of glutamatergic transmission on the acquisition of T-maze and radial maze tasks
(1989) Hauber, Wolfgang; Schmidt, Werner J.
Prefrontal cortex and neostriatum constituting the prefrontal system are connected by glutamatergic neurones. The involvement of this corticostriatal projection in control of maze performance of rats was investigated. Glutamatergic transmission mediated by N-methyl-D-aspartate (NMDA) receptors was blocked by intrastriatal injections of dl-2-amino-5-phosphonovaleric acid (AP-5) (50 nmole in 0.5 Mgrl). In experiment 1, intrastriatal AP-5 was found to increase the number of errors during acquisition of a delayed alternation task in a T-maze. In experiment 2, the effect of intrastriatal AP-5 on acquisition of different 8 arm maze tasks was investigated. AP-5 did not affect the number of reentries on spontaneous and reinforced alternation; pre- and postdelay errors on delayed alternation were not altered. Therefore, intrastriatal NMDA receptor blockade impairs acquisition of a delayed alternation in a T-maze, while intrastriatal blockade of NMDA receptors does not affect acquisition of different 8 arm maze tasks.
Open Access
Excitatory amino acid antagonists and Parkinson's disease [Reply to letter to the editor]
(1990) Schmidt, Werner J.; Bubser, Michael; Hauber, Wolfgang
Girault et al. draw similar conclusions from their studies of the regulation of protein phosphorylation by dopamine and glutamate in striatonigral neurones as we did on the basis of behavioural findings, i.e. that dopamine and glutamate may exert opposite effects within the neostriatum. Admittedly, this view is oversimplified, but this transmitter balance does seem to be relevant to the parkinsonian symptoms akinesia and rigidity.
Open Access
Excitatory amino acids and Parkinson's disease [Letter to the editor]
(1990) Schmidt, Werner J.; Bubser, Michael; Hauber, Wolfgang
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Open Access
The NMDA antagonist dizocilpine (MK-801) reverses haloperidol-induced movement initiation deficits
(1990) Hauber, Wolfgang; Schmidt, Werner J.
The present study shows that systemic dopamine receptor blockade impaired movement initiation of rats, trained in a simple reaction time task for rapid initiation of locomotion in response to a combined optic/acoustic cue. Reaction time, movement time and the accelerative force were recorded for each initiation of locomotion. Results indicate a dose-related increase of reaction time following systemic administration of haloperidol (0.1, 0.15, 0.3 mg/kg i.p.). Measures derived from resulting force-time patterns showed a haloperidol-induced decrease (0.15 mg/kg i.p.) of the mean rate of force development, indicating a decreased initial acceleration. These effects were reversed by systemic co-administration of dizocilpine (MK-801) (0.08 mg/kg i.p.), a selective non-competitive N-methyl-d-aspartate (NMDA) antagonist. The haloperidol-induced movement initiation deficits in this task are in part comparable to akinesia seen in Parkinson's disease and their reversal by dizocilpine has implications for the treatment of this disease.