Browsing by Author "Hauber, Wolfgang"

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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
The AMPA antagonist GYKI 52466 reverses the anticataleptic effects of the competitive NMDA antagonist CGP 37849
(1994) Hauber, Wolfgang; Waldenmeier, Marc T.
The effects of the AMPA receptor antagonist GYKI 52466 (1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine HCl) on haloperidol-induced catalepsy were tested in drug-naive rats and in rats pretreated with the competitive NMDA receptor antagonist CGP 37849 (DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid). CGP 37849 (4 mg/kg i.p.) given alone significantly reversed haloperidol-induced catalepsy (0.5 mg/kg i.p.) while GYKI 52466 (4.8 mg/kg i.p.) given alone was without effect. Administration of GYKI 52466 to rats pretreated with CGP 37849 abolished the anticataleptic effects of the competitive NMDA receptor antagonist seen following single administration. Thus the AMPA receptor antagonist prevents behavioural effects induced by a NMDA receptor antagonist in this behavioral model.
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
Clozapine improves dizocilpine-induced delayed alternation impairment in rats
(1993) Hauber, Wolfgang
The effects of systemic administration of dizocilpine (0.16mg/kg, i.p.), clozapine (7.5mg/kg, s.c.) and coadministration of dizocilpine (0.16mg/ kg, i.p.) and clozapine (7.5mg/kg, s.c.) on acquisition of delayed alternation in a T-maze were tested in rats (N=7 per group) on six days with 10 choices per day and animal. Clozapine given alone did not impair delayed alternation learnint, except of the first day. Dizocilpine induced a significant delayed alternation impairment on all days tested. Pretreatment with clozapine significantly improved the dizocilpine-induced impairment. Treatment-induced changes of delayed alternation learning and of locomotor activities showed no correlation. The results demonstrate that clozapine functionally compensated for deficits induced by a blockade of the N-methyl-D-asparatate (NMDA) subtype of glutamate receptors.
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
Dopamine D1/D2 receptor activity in the nucleus accumbens core but not in the nucleus accumbens shell and orbitofrontal cortex modulates risk-based decision making
(2015) Mai, Bettina; Sommer, Susanne; Hauber, Wolfgang
Background: It is well known that brain dopamine (DA) signals support risk-based decision making; however, the specific terminal regions of midbrain DA neurons through which DA signals mediate risk-based decision making are unknown. Methods: Using microinfusions of the D1/D2 receptor antagonist flupenthixol, we sought to explore the role of D1/D2 receptor activity in the rat orbitofrontal cortex (OFC) and core and shell regions of the nucleus accumbens (AcbC and AcbS, respectively) in the regulation of risky choices. A risk-discounting task was used that involves choices between a certain small-reward lever that always delivered 1 pellet or a risky large-reward lever which delivered 4 pellets but had a decreasing probability of receiving the reward across 4 subsequent within-session trial blocks (100%, 50%, 25%, 12.5%). To validate task sensitivity to experimental manipulations of DA activity, we also examined the effects of systemic amphetamine and flupenthixol. Results: Systemic amphetamine increased while systemic flupenthixol reduced risky choices. Results further demonstrate that rats that received intra-AcbC flupenthixol were able to track increasing risk associated with the risky lever but displayed a generally reduced preference for the risky lever across all trial blocks, including in the initial trial block (large reward at 100%). Microinfusions of flupenthixol into the AcbS or OFC did not alter risk-based decision making. Conclusions: Our data suggest that intra-AcbC D1/D2 receptor signaling does not support the ability to track shifts in reward probabilities but does bias risk-based decision making. That is, it increased the rats’ preference for the response option known to be associated with higher risk-related costs.
Open Access
Dopamine D1/D2 receptors do not mediate the expression of conditioned place preference induced by the aftereffect of wheel running
(2014) Trost, Alexandra; Hauber, Wolfgang
Background Rats lever-press for access to running wheels suggesting that wheel running by itself is reinforcing. Furthermore, pairings of an episode of wheel running and subsequent confinement in a specific environment can establish a conditioned place preference (CPP). This finding implies that the reinforcing effects of wheel running outlast the actual occurrence of physical activity, a phenomenon referred to as aftereffect of wheel running. Aftereffect-induced CPP involves Pavlovian conditioning, i.e. repeated pairings of the aftereffect of wheel running with a specific environment creates a learned association between aftereffect and environment and, in turn, a preference for that environment. Given the involvement of dopamine systems in mediating effects of Pavlovian stimuli on appetitive behavior, a role of dopamine in mediating aftereffect-induced CPP seems plausible. Here we assessed whether the mixed D1/D2 receptor antagonist flupenthixol (0.25 mg/kg, i.p.) can block the expression of an aftereffect-induced CPP. Results In line with earlier studies, our results demonstrate that rats displayed a conditioned preference for environments paired with the aftereffect of wheel running and further show that the magnitude of CPP was not related to the wheel running rate. Furthermore, we found that flupenthixol (0.25 mg/kg, i.p.) reduced locomotor activity but did not attenuate the expression of an aftereffect-induced CPP. Conclusion The expression of a CPP produced by the aftereffect of wheel running seems not to depend on dopamine D1/D2 receptor activation.
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
Effects of motivational downshifts on specific Pavlovian-instrumental transfer in rats
(2022) Sommer, Susanne; Münster, Alexandra; Fehrentz, Jean-Alain; Hauber, Wolfgang
Konditionierte Umweltreize, die mit attraktiven Nahrungsmitteln assoziiert sind, können die Nahrungsaufnahme offenbar auch dann anregen, wenn dafür keine physiologische Notwendigkeit besteht, etwa bei Sättigung. Man vermutet, dass ein solcher Mechanismus Überwicht und Adipositas fördert. Unsere aktuelle Arbeit hat diese Annahme an Labornagetieren eingehend überprüft. Aus den Messungen geht übereinstimmend hervor, dass der stimulierende Einfluss von konditionierten Umweltreizen auf nahrungsbezogene Handlungen bei Sättigung massiv annahm. Unsere Ergebnisse stehen also nicht in Einklang mit der Annahme, dass das Belohnungssystem bei Darbietung von konditionierten, nahrungsprädiktiven Umweltreizen eine bestehende Sättigung überspielt und nahrungsbezogene Handlungen automatisch in Gang setzt.
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.
Open Access
The non-NMDA glutamate receptor antagonist GYKI 52466 counteracts locomotor stimulation and anticataleptic activity induced by the NMDA antagonist dizocilpine
(1993) Hauber, Wolfgang; Andersen, Ragna
The effects of the non-NMDA glutamate receptor antagonist GYKI 52466 (2.4 and 4.8 mg/kg, i.p.) on spontaneous locomotor activity and haloperidol-induced catalepsy (0.5 mg/kg, i.p.) were assessed in naive rats and in rats pretreated with the NMDA antagonist dizocilpine (0.08 mg/kg, i.p.). GYKI 52466 given alone did not alter locomotor activity and haloperidol-induced catalepsy, but significantly antagonized the dizocilpine-induced locomotor stimulation and counteracted the anti-cataleptic effects of dizocilpine on haloperidol-induced catalepsy. Thus blockade of non-NMDA glutamate receptors antagonized the behavioural stimulant effects of a NMDA receptor blockade.
Open Access
A novel reaction time task for investigating force and time parameters of locomotor initiation in rats
(1990) Hauber, Wolfgang
A novel simple reaction-time task for rats is described in the present study. Food-deprived rats were trained in a modified runway for rapid locomotor initiation, in response to a combined optical/acoustic stimulus, to receive a food reward. Rats rapidly learned this task with small variability, and movement patterns of locomotor initiation are congruent under these conditions. Reaction time, movement time and accelerative forces were recorded from each initiation of locomotion by means of video equipment and a force platform. The quantification modes yielded consistent results and a quantitative description of measured force and time parameters is given. The task may be especially appropriate for investigating basal ganglia functions. The present results will be the basis for investigating initiation of locomotion in animal models of neurological diseases.
Open Access
Role of the medial orbitofrontal cortex and ventral tegmental area in effort-related responding
(2020) Münster, Alexandra; Votteler, Angeline; Sommer, Susanne; Hauber, Wolfgang
Die Arbeit untersucht die Interaktion von zwei Gehirnarealen, dem medialen Orbitofrontalcortex und dem Ventralen Tegmentalen Areal, bei der Handlungssteuerung.