Minocycline attenuates hyperlocomotion and prepulse inhibition deficits in mice after administration of the NMDA receptor antagonist dizocilpine.
The present study was undertaken to examine whether the second generation antibiotic drug minocycline attenuates behavioral changes (eg, acute hyperlocomotion and prepulse inhibition (PPI) deficits) in mice after the administration of the N-methyl-D-aspartate (NMDA) receptor antagonist (+)-MK-801 (dizocilpine). Dizocilpine (0.1 mg/kg)-induced hyperlocomotion was significantly attenuated by pretreatment with minocycline (40 mg/kg). Furthermore, the PPI deficits after a single administration of dizocilpine (0.1 mg/kg) were attenuated by pretreatment with minocycline (10, 20, or 40 mg/kg), in a dose-dependent manner. Moreover, in vivo microdialysis study in the free-moving mice revealed that pretreatment with minocycline (40 mg/kg, i.p.) significantly attenuated the increase of extracellular dopamine (DA) levels in the frontal cortex and striatum after administration of dizocilpine (0.1 mg/kg), suggesting that the inhibition of dizocilpine-induced DA release by minocycline may, at least in part, be implicated in the mechanism of action of minocycline with respect to dizocilpine-induced behavioral changes in mice. These findings suggest that minocycline could attenuate behavioral changes in mice after the administration of the NMDA receptor antagonist dizocilpine. Therefore, it is possible that minocycline would be a potential therapeutic drug for schizophrenia.
Zhang
Lin
L
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba 260-8670, Japan.
Shirayama
Yukihiko
Y
Iyo
Masaomi
M
Hashimoto
Kenji
K
D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D005625:Frontal Lobe / Q000187:drug effects; D020233:Gait Disorders, Neurologic / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008911:Minocycline / Q000627:therapeutic use*; D009433:Neural Inhibition / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D016291:Dizocilpine Maleate; D008911:Minocycline; D004298:Dopamine