Thomas M. Tzschentke
Ein paar biographische Angaben:
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geb. 20.01.1969 in Aalen
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1988-1990 Grundstudium Biologie in Tⁿbingen
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1990-1991 Studienjahr an der University of Sussex in Brighton/GB
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1991-1994 Hauptstudium Biologie in Tⁿbingen mit den FΣchern Tierphysiologie, Pharmakologie, Physiologische Psychologie, Parasitologie
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1994/95 Diplomarbeit in der Abteilung Neuropharmakologie mit dem Titel:
Der Einflu▀ von Glutamat-Antagonisten auf Morphin-induzierte Katalepsie, konditionierte PlatzprΣferenz und Sensitivierung bei der Ratte
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1995-1996 Doktorarbeit in der Abteilung Neuropharmakologie mit dem vorlΣufigen Titel:
Die Rolle glutamaterger Neurotransmission bei Belohnungs- und Sensitivierungsprozessen, mit besonderer Berⁿcksichtigung des medialen prΣfrontalen Cortex
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voraussichtlich noch bis 9/97 Forschungsaufenthalt am Center for Studies in Behavioral Neuroscience (Prof. Roy Wise), Concordia University, MontrΘal, Kanada
Bisherige Publikationen:
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Bubser, M., Tzschentke, T.M. and Hauber, W. (1995)
Behavioural and neurochemical interactions of the AMPA antagonist GYKI 52466 and the non-competitive NMDA antagonist dizocilpine in rats. Journal of Neural Transmission [P-D Sect] 101, 115-126.
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Tzschentke, T.M. and Schmidt, W.J. (1995)
N-Methyl-D-aspartic acid-receptor antagonists block morphine-
induced conditioned place preference in rats. Neuroscience Letters 193, 37-40.
Abstract:
We addressed the question of whether (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) and DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP37849), a non-competitive and a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, respectively, are able to block morphine-induced conditioned place preference (CPP). MK-801 alone (0.1 mg/kg) produced neither a place preference nor a place aversion, but was able to completely block morphine-induced CPP. CGP37849 alone (10 mg/kg) produced a small but significant CPP, and was able to significantly attenuate morphine-induced CPP.
These results can not be due to simple additive effects of drug actions, but suggest that NMDA-receptors play a complex role in the development of morphine CPP.
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Tzschentke, T.M. and Schmidt, W.J. (1996)
Morphine-induced catalepsy is augmented by NMDA receptor antagonists, but is partially attenuated by an AMPA receptor antagonist. European Journal of Pharmacology 295, 137-146.
Abstract:
High doses of morphine produce a state of behavioural inactivity and muscular rigidity. This type of "catalepsy" is clearly different from the state which is produced by the administration of neuroleptics, e.g. haloperidol. While haloperidol-induced catalepsy can easily be antagonised by N-methyl-D-aspartate (NMDA) receptor antagonists, there has been a report that the non-competitive NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) potentiates morphine-induced catalepsy.The aim of this study was to further examine the role of glutamate receptors in the mediation of morphine-induced catalepsy. To this end we coadministered morphine (20, 40, 60 mg/kg, i.p.) with MK-801 (0.1 and 0.3 mg/kg, i.p.), the competitive NMDA receptor antagonist DL-(E)-2-amino-4-methyl-5-phosphono-3-pentoic acid (CGP 37849) (2 and 6 mg/kg, i.p.), or 1-(4-aminophenyl)-4-methyl-7,8-methylen-dioxy-5H-2,3-benzodiazepine (GYKI 52466) (2 and 4 mg/kg), an antagonist of the *-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid (AMPA) type of glutamate receptors, respectively.The degree of catalepsy was assessed using two different methods, the "bar/podium/grid"-test which is commonly used to measure neuroleptic-induced catalepsy, and a test for the presence or absence of righting reflexes after turning the animals into a supine position.
It was found that in the "bar/podium/grid"-test coadministration of both NMDA receptor antagonists significantly and dose-dependently augmented morphine-induced catalepsy. The results using the AMPA receptor antagonist were less clear since the lower dose of GYKI 52466 tended to attenuate the morphine effect whereas the higher dose augmented morphine-induced catalepsy in some cases. While placing the animals on the bar and on the podium produced essentially the same results, the grid was found to be inapplicable for the measurement of morphine-induced catalepsy since the animals did not cling to the grid and fell off almost immediately after being released from the experimenter┤s hand.With respect to the righting reflexes it was found that the number of animals not showing these responses increased when MK-801 or CGP 37849 was coadministered with morphine. In contrast, most of the animals treated with GYKI 52466 and morphine displayed intact righting reflexes.
It is concluded that glutamatergic transmission plays an important role in the mediation of morphine-induced catalepsy, though different to that of haloperidol-induced catalepsy, and that NMDA and AMPA receptors are differentially involved in different aspects of the associated behavioural state.
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Tzschentke, T.M. and Schmidt, W.J. (1996)
Procedural examination of behavioural sensitisation to morphine:
lack of blockade by MK-801, occurrence of sensitised sniffing, and evidence for cross-sensitisation between
morphine and MK-801. Behavioural Pharmacology 7, 169-184.
Abstract:
Rats were tested in an open field, a "sniffing box" and an eight-arm maze to examine in detail the behavioural changes induced by morphine (10 mg/kg, i.p.) and MK-801 (0.1 mg/kg, i.p.), either alone or in combination,
during a 10 day treatment and subsequent drug challenges. In addition to locomotion a number of other behaviours
such as sniffing, rearing and exploration were examined.After morphine challenge sensitized locomotion and rearing was found in the open field and sensitized sniffing and turning was observed in the sniffing box. In addition, in the sniffing box saline challenge produced significant conditioned sniffing and turning, and after a challenge with MK-801 sensitized sniffing and turning was seen in
the group pretreated with morphine, suggesting a cross-sensitization between morphine and MK-801 (but not vice
versa). In the eight-arm maze, sensitized locomotion was found after morphine challenge. Morphine and MK-801
changed the preference for particular angles run during trials in a characteristic manner.
In none of the behavioural measures was MK-801 able to block the development (and expression) of sensitization
to morphine. In several cases MK-801 rather enhanced the acute morphine effects. Sensitization of sniffing
suggests that sensitization has also developped within the nigrostriatal dopamine system and not only within the
mesolimbic dopamine system, as is generally discussed in the context of the most commonly assessed locomotion.
This finding argues for the additional use of the sniffing box in sensitization experiments.
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Document last modified 16. October 1996
