Dr. Beate D. Kretschmer
Some biographical details:
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1991 Diploma in Biology: "Behavioral pharmacology of the strychnine-insensitive glycine site of the NMDA receptor complex"
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1994 PhD in Biology: "Control of motor behavior via the strychnine-insensitive glycine site of the NMDA receptor complex in the basal ganglia of the rat"
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since 1994 Research Scientist in the SFB 307 of the Deutsche Forschungsgemeinschaft
Topic: Effects of ligands acting at the strychnine-insensitive glycine binding site of the NMDA receptor complex and at the competitive and non-competitive NMDA receptor.
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Methods: Behavioral and neurochemical analyses of motor and cognitive behavior.
Animal models of locomotion, stereotypy, prepulse inhibition and learning.
One- and two-probe microdialysis and analysis of catecholamines with electrochemical HPLC.
Recent publications:
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Kretschmer B.D., Bubser M., Schmidt W.J. (1995)
Behavioral and neurochemical actions of the strychnine-insensitive glycine binding site ,antagonist, 7-chlorokynurenate, in rats.
Eur. J. Pharmacol. 280, 37-45.
Abstract:
The present study investigated if blockade of the modulatory glycine receptor of the
NMDA receptor complex influences the expression of behavior (sniffing stereotypy and
locomotion) and dopamine metabolism in rats as it has been shown for NMDA receptor
antagonists. The glycine receptor antagonist, 7-chlorokynurenate (7-chloro-4-
hydroxyquinoline-2-carboxylic acid), induced a dose-dependent sniffing stereotypy but
had no effect on locomotion when it was given i.c.v.. The glycine receptor agonist, D-
cycloserine (D-4-amino-3-isoxazolidinone), antagonized the sniffing stereotypy. 7-
chlorokynurenate had no influence on dopamine metabolism in the striatum and the
nucleus accumbens, but moderately decreased the metabolism in the prefrontal cortex.
Comparison of behavioral and neurochemical outcomes suggests that the failure to induce
locomotion correlates with the unchanged dopamine metabolism in the basal ganglia,
while sniffing stereotypy does not. These results show that blockade of the glycine
receptor of the NMDA receptor complex induces a behavioral and neurochemical profile
similar to that with competitive NMDA receptor antagonists.
Keywords:
glycine, NMDA, schizophrenia, dopamine metabolism, stereotypy
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Kretschmer B.D., Schmidt W.J. (1996)
Behavioral effects mediated by the modulatory glycine site of the NMDA receptor in the anterodorsal striatum and nucleus accumbens. J. Neurosci. 16 (4), 1561-1569.
Abstract:
The striatum and the nucleus accumbens are the main input structures of the basal ganglia
(BG). They contribute differently to motor behavior controlled by the BG in rats, e.g.
stereotyped behavior, catalepsy and locomotion. While the striatum is predominantly
involved in the control of sniffing behavior and catalepsy, the nucleus accumbens
contributes to control of locomotion. To test whether the allosteric glycine site of the N-
methyl-D-aspartate (NMDA) receptor complex modulates these behavioral variables, we
injected the glycine site antagonist 7-chlorokynurenate and the glycine site agonist D-
serine into the anterodorsal striatum and the nucleus accumbens and studied their
influence on stereotypical snout contacts and locomotion. Additionally, the effects of
intrastriatal injections of 7-chlorokynurenate on haloperidol- and SCH 23390-induced
catalepsy were investigated. 7-Chlorokynurenate enhanced stereotypical snout contacts in
the anterodorsal striatum and in the nucleus accumbens but did not change spontaneous
locomotion in either of these structures. Haloperidol- but not SCH 23390-induced
catalepsy was attenuated by intrastriatally administered 7-chlorokynurenate. The glycine
site agonist, D-serine, had no effect on stereotypical snout contacts and locomotion. The
results suggest that motor behavior mediated by the striatopallidal output pathway is
modulated by the glycine site, while motor behavior mediated by the accumbopallidal and
striatonigral output pathway is not.
Keywords:
stereotypy, locomotion, striatum, nucleus accumbens, NMDA, glycine, 7-
chlorokynurenate, D-serine
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Schmidt W.J., Kretschmer B.D. (1996)
Behavioural pharmacology of glutamate receptors in the basal ganglia. Neurosci. Biobehav. Rev., submitted
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Kretschmer B.D., Koch M. (1996)
Role of the strychnine-insensitive glycine receptor in the nucleus accumbens and anterodorsal striatum on sensorimotor gating: a behavioral and microdialysis study. Psychopharmacology, submitted
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Document last modified 16. October 1996
