Abstract
Aim:
To examine the effect of GNTI [5′-guanidinyl-17-(cyclopropylmethyl)-6,7-dehydro-4,5α-epoxy-3,14-dihydroxy-6,7-2′,3′-indolomorphinan], a selective antagonist for the kappa opioid receptor, in the MK-801 (dizocilpine maleate)-induced behavioral model of psychosis in schizophrenia as a way to explore the involvement of the kappa opioid receptor in modulating psychotic symptoms of schizophrenia.
Methods:
Two doses of MK-801 (0.3 mg/kg and 0.6 mg/kg) were administered by systemic injection in mice to induce psychosis-like behavior as a rodent schizophrenia model, preceded by an injection of different doses of GNTI. Both locomotion and stereotypy were measured as the behavioral endpoints for quantitative analysis.
Results:
GNTI inhibited MK-801-induced hyperlocomotion and stereotypy. In particular, GNTI showed differential modulation of stereotypy induced by 0.3 mg/kg vs 0.6 mg/kg MK-801.
Conclusion:
Antagonism of kappa opioid receptors attenuates MK-801-induced behavior, suggesting a potential involvement of the kappa opioid receptor in psychosis-like symptoms of schizophrenia. GNTI appears to be a useful pharmacological tool to explore the kappa opioid receptor function in vivo.
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Project supported by grant from the National Natural Science Foundation of China (No 30270219).
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Qi, Ct., Zou, H., Zhang, Ch. et al. Effect of GNTI, a kappa opioid receptor antagonist, on MK-801-induced hyperlocomotion and stereotypy in mice. Acta Pharmacol Sin 27, 1401–1408 (2006). https://doi.org/10.1111/j.1745-7254.2006.00448.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00448.x
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