Dr. Beate D. Kretschmer
Ein paar biographische Angaben:
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1991 Diplom in Biologie: "Verhaltenspharmakologische Untersuchungen zur Wirkungsweise des Glycinrezeptors"
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1994 Doktor in Biologie: "Verhaltenssteuerung durch den strychnin-insensitiven Glycinrezeptor in den Basalganglien der Ratte"
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seit 1994 wissenschaftlicher Mitarbeiter des SFB 307 der Deutschen Forschungsgemeinschaft
Thema: Effekte von Liganden am strychnin-insensitiven Glycinrezeptor und kompetitiven und nicht-kompetitiven Bindungsstellen des NMDA-Rezeptor-Komplexes
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Methoden: Verhaltenspharmakologische und neurochemische Untersuchungen von motorischen und
kognitiven Prozessen.
Tiermodelle der Lokomotion, Stereotypie, Prepuls-Inhibition und des Lernens.
Mikrodialyse mittels ein- und zwei-Sonden Systemen und die Analyse von Katecholaminen.
Aktuelle Publikationen:
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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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Beate D. Kretschmer
1
and Michael Koch
2
(1997)
Role of the strychnine-insensitive glycine binding site in the nucleus accumbens and anterodorsal striatum in sensorimotor gating: a behavioral and microdialysis study. Psychopharmacology, 130, 131-138.
1
Abteilung Neuropharmakologie, UniversitΣt Tⁿbingen, Mohlstr. 54/1, 72074 Tⁿbingen, Germany
2
Tierphysiologie, UniversitΣt Tⁿbingen, Auf der Morgenstelle 28, 72076 Tⁿbingen, Germany
Abstract:
This study examined the role of the strychnine-insensitive glycine binding site of the NMDA receptor in prepulse inhibition (PPI) of the acoustic startle response (ASR) in rats. PPI is an operational measure of gating processes which normally lead to a diminished ASR when a startling stimulus is preceded by a weak prepulse. PPI is impaired in schizophrenics and, therefore, experimentally induced PPI-deficits in rats can be regarded as model for gating deficits in schizophrenia. Local administration of 7-chlorokynurenate (7-CLKYN), an antagonist of the strychnine-insensitive glycine site of the NMDA receptor, into the nucleus accumbens reduced PPI. This sensorimotor gating deficit was antagonized by systemic pretreatment of the rats with the glycine site agonist D-cycloserine, indicating that the effect of 7-CLKYN was due to a blockade of the NMDA receptor associated glycine binding site. A similar deficit in PPI was observed after intraaccumbal administration of the competitive NMDA receptor antagonist AP-5. PPI was normal after injecting these drugs into the anterodorsal striatum. The hypothesis that the PPI-deficit is accompanied by an increased dopamine release was tested by a neurochemical analysis of the effects of local injection of 7-CLKYN. Microdialysis data showed no increase of accumbal and striatal dopamine release after blockade of the glycine site with 7-CLKYN. Our data demonstrate that the glycine/NMDA receptor in the nucleus accumbens plays a important role in sensorimotor information processing that depends not on a hyperactive dopamine system.
Keywords:
Acoustic startle response, Anterodorsal striatum, Dopamine, Glycine, NMDA, Nucleus accumbens, Prepulse inhibition, AP-5, 7-chlorokynurenate, Rat
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Schmidt W.J., Kretschmer B.D. (1997)
Behavioural pharmacology of glutamate receptors in the basal ganglia. Neurosci. Biobehav. Rev., in press
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Kretschmer BD, Kratzer U, Breithecker K, Koch M (1997)
ACEA 1021, a glycine site antagonist with minor psychotomimetic and amnestic side effects in rats. Eur J Pharmacol., in revision
Stand 21.04.1997
