Minocycline, a second-generation tetracycline, as a neuroprotective agent in an animal model of schizophrenia.
Minocycline is a second-generation tetracycline with a distinct neuroprotective profile. The current study assessed the effects of minocycline in an animal model of schizophrenia, the non-competitive NMDA antagonist (dizocilpine maleate; MK801). The effects of minocycline were compared to those of haloperidol, a dopamine antagonist used for the treatment of schizophrenia. The study protocol involved daily intraperitoneal injections of minocycline (35 mg/kg) for three consecutive days. On the fourth day, the rats were injected with MK801 and assessed for visual-spatial memory (Morris water maze) and sensorimotor gating (acoustic startle response, ASR, and the prepulse inhibition of the ASR). The findings indicate that MK801 caused cognitive visuo-spatial memory deficits and changes in sensorimotor gating, similar to those evident in schizophrenia. Minocycline reversed these cognitive effects of MK801 and this effect was similar to that of haloperidol. The results of this study suggest that minocycline may have protective properties against the cognitive effects of the MK801 animal model of schizophrenia. The discussion addresses potential mechanisms underlying the effects of minocycline and possible directions for future research.
Levkovitz
Yechiel
Y
The Emotion-Cognition Research Center, The Shalvata Mental Health Care Center, P.O.B. 94. Hod-Hasharon, Israel. ylevk@clalit.org.il
Levi
Uri
U
Braw
Yoram
Y
Cohen
Hagit
H
D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008911:Minocycline / Q000627:therapeutic use*; D009433:Neural Inhibition / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects; D012559:Schizophrenia / Q000503:physiopathology* / Q000517:prevention & control*; D013997:Time Factors
D018696:Neuroprotective Agents; D008911:Minocycline