Effect of GNTI, a kappa opioid receptor antagonist, on MK-801-induced hyperlocomotion and stereotypy in mice.
OBJECTIVE
To examine the effect of GNTI [5'-guanidinyl-17-(cyclopropylmethyl)-6,7- dehydro-4,5alpha-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.


CONCLUSIONS
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.
Qi
Chun-ting
CT
Research Center for Biotechnology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200233, China.
Zou
Hong
H
Zhang
Chen-hao
CH
Xie
Qing-lian
QL
Jin
Mei-lei
ML
Yu
Lei
L
D000818:Animals; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors*; D006146:Guanidines / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009019:Morphinans / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D012559:Schizophrenia / Q000503:physiopathology; D013239:Stereotyped Behavior / Q000187:drug effects*
C411465:17-cyclopropylmethyl-6,7-didehydro-4,5-epoxy-5'-guanidinyl-3,14-dihydroxyindolo(2',3'-6,7)morphinan; D006146:Guanidines; D009019:Morphinans; D017473:Receptors, Opioid, kappa; D016291:Dizocilpine Maleate