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MK‐801 prevents the development of behavioral sensitization during repeated morphine administration

MK‐801 prevents the development of behavioral sensitization during repeated morphine administration Acute administration of morphine (10 mg/kg) to rats elicited an increase in locomotion that became sensitized upon repeated treatment over 14 days. Administration of the noncompetitive N‐methyl‐D‐aspartate receptor (NMDA) antagonist MK‐801 (0.1 or 0.25 mg/kg) prior to each morphine injection prevented the development of behavioral sensitization to morphine, an effect that persisted even after a 7‐day withdrawal from repeated treatment. Sensitization was also prevented by coadministration of the competitive NMDA receptor antagonist CGS 19755 (10 mg/kg). In contrast, acute pretreatment with MK‐801 did not alter the response of sensitized rats to morphine challenge, indicating that MK‐801 does not prevent the expression of sensitization. When administered alone, MK‐801 produced stereotyped movements at moderate doses (0.25 rng/kg) and horizontal locomotion at higher‐ doses, (0.5 mg/kg). Repeated administration of 0.25 mg/kg MK‐801 elicited sensitization to its own locomotor stimulatory effects, such that this dose became capable of eliciting horizontal locomotion. Sensitization was not seen during repeated administration of 0.1 mg/kg MK‐801 or 10 mg/kg CGS 19755, although both of these pretreatments did produce a sensitized response to subsequent challenge with 0.25 mg/kg MK‐801. This effect was enhanced by coadministration of morphine, even though repeated administration of morphine alone failed to sensitize rats to MK‐801 challenge. These results suggest a complex interplay between NMDA and opioid receptors, such that NMDA antagonists prevent morphine sensitization while morphine enhances the ability of NMDA antagonists to elicit sensitization to their own locomotor stimulatory effects. © 1994 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Synapse Wiley

MK‐801 prevents the development of behavioral sensitization during repeated morphine administration

Synapse , Volume 16 (2) – Feb 1, 1994

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References (65)

Publisher
Wiley
Copyright
Copyright © 1994 Wiley‐Liss, Inc.
ISSN
0887-4476
eISSN
1098-2396
DOI
10.1002/syn.890160207
pmid
8197575
Publisher site
See Article on Publisher Site

Abstract

Acute administration of morphine (10 mg/kg) to rats elicited an increase in locomotion that became sensitized upon repeated treatment over 14 days. Administration of the noncompetitive N‐methyl‐D‐aspartate receptor (NMDA) antagonist MK‐801 (0.1 or 0.25 mg/kg) prior to each morphine injection prevented the development of behavioral sensitization to morphine, an effect that persisted even after a 7‐day withdrawal from repeated treatment. Sensitization was also prevented by coadministration of the competitive NMDA receptor antagonist CGS 19755 (10 mg/kg). In contrast, acute pretreatment with MK‐801 did not alter the response of sensitized rats to morphine challenge, indicating that MK‐801 does not prevent the expression of sensitization. When administered alone, MK‐801 produced stereotyped movements at moderate doses (0.25 rng/kg) and horizontal locomotion at higher‐ doses, (0.5 mg/kg). Repeated administration of 0.25 mg/kg MK‐801 elicited sensitization to its own locomotor stimulatory effects, such that this dose became capable of eliciting horizontal locomotion. Sensitization was not seen during repeated administration of 0.1 mg/kg MK‐801 or 10 mg/kg CGS 19755, although both of these pretreatments did produce a sensitized response to subsequent challenge with 0.25 mg/kg MK‐801. This effect was enhanced by coadministration of morphine, even though repeated administration of morphine alone failed to sensitize rats to MK‐801 challenge. These results suggest a complex interplay between NMDA and opioid receptors, such that NMDA antagonists prevent morphine sensitization while morphine enhances the ability of NMDA antagonists to elicit sensitization to their own locomotor stimulatory effects. © 1994 Wiley‐Liss, Inc.

Journal

SynapseWiley

Published: Feb 1, 1994

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