TITLE:
Doxycycline Ameliorates Schizophrenia-Like Behaviors in Experimental Models in Mice by Targeting Underlying Oxidative Stress
AUTHORS:
Benneth Ben-Azu, Itivere Adrian Omogbiya, Adegbuyi Oladele Aderibigbe, Solomon Umukoro, Abayomi Mayowa Ajayi, Aya-Ebi Okubo Eneni, Ezekiel O. Iwalewa
KEYWORDS:
Schizophrenia, Antipsychotics, Oxidative Stress, Antioxidant, Doxycycline
JOURNAL NAME:
Journal of Behavioral and Brain Science,
Vol.6 No.13,
December
13,
2016
ABSTRACT: Current evidences support the inhibition of oxidative and inflammatory signaling mechanisms in the treatment of schizophrenia; as cure for this disease still remains limited. Doxycycline is a tetracycline antibiotic (a minocycline congener) with strong antioxidant and anti-inflammatory properties, and better pharmacokinetic profiles. Preclinical evidence indicates that minocycline possesses antipsychotic properties. This present study was designed to evaluate the effect of doxycycline on schizophrenia-like behaviors, as well as biomarkers of oxidative stress in mice brains. Novelty-induced rearing (NIR) behavior was used to evaluate the tranquilizing effect of doxycycline (25 - 200 mg/kg). The acute antipsychotic effects of doxycycline were assessed using apomorphine-induced stereotypy, ketamine-induced stereotypy, hyperlocomotion and enhanced immobility in forced swim test (FST). Catalepsy test was also employed to evaluate the extrapyramidal adverse effect of doxycycline in mice. The chronic antipsychotic effect of doxycycline was evaluated following oral administration of doxycycline in combination with ketamine (100 mg/kg) intraperitoneally for 10 days. Twenty four hours after the last administration, positive (locomotor activity), cognitive (Y-maze) and negative (FST) symptoms were assessed. Thereafter, levels of biomarkers of oxidative stress were evaluated in mice brains. Doxycycline significantly (P P P