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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 antago-nist for the kappa opioid receptor,in the MK-801(dizocilpine maleate)-inducedbehavioral model of psychosis in schizophrenia as a way to explore the involve-ment of the kappa opioid receptor in modulating psychotic symptoms ofschizophrenia.Methods:Two doses of MK-801(0.3 mg/kg and 0.6 mg/kg)wereadministered by systemic injection in mice to induce psychosis-like behavior as arodent schizophrenia model,preceded by an injection of different doses of GNTI.Both locomotion and stereotypy were measured as the behavioral endpoints forquantitative analysis.Results:GNTI inhibited MK-801-induced hyperlocomotionand stereotypy.In particular,GNTI showed differential modulation of stereotypyinduced by 0.3 mg/kg vs 0.6 mg/kg MK-801.Conclusion:Antagonism of kappaopioid receptors attenuates MK-801-induced behavior,suggesting a potentialinvolvement of the kappa opioid receptor in psychosis-like symptoms ofschizophrenia.GNTI appears to be a useful pharmacological tool to explore thekappa opioid receptor function in vivo.
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 antago-nist for the kappa opioid receptor, in the MK-801 (dizocilpine maleate) -inducedbehavioral model of psychosis in schizophrenia as a way to explore the involvement-ment 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) wereadministered by systemic injection in mice to induce psychosis-like behavior as arodent schizophrenia model, preceded by an injection of different doses of GNTI.Both locomotion and stereotypy were GNTI showed differential modulation of stereotypy induced by 0.3 mg / kg vs 0.6 mg / kg MK-801.Conclusion: Antagonism of kappaopioid receptors attenuates MK -801-induced behavior, suggesting a potential involvem ent of the kappa opioid receptor in psychosis-like symptoms ofschizophrenia. GNTI appears to be a useful pharmacological tool to explore thekappa opioid receptor function in vivo.