Author(s)

Benneth Ben-Azu¹, Itivere Adrian Omogbiya^1,2*, Adegbuyi Oladele Aderibigbe¹, Solomon Umukoro¹, Abayomi Mayowa Ajayi¹, Aya-Ebi Okubo Eneni¹, Ezekiel O. Iwalewa¹

¹Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria.
²Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, Delta State University, Abraka, Nigeria.

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 < 0.05) decreased NIR, inhibited stereotypy induced by apomorphine and ketamine. Additionally, doxycycline significantly (P < 0.05) prevented ketamine-induced hyperlocomotion, cognitive deficit and reduced enhanced-immobility by ketamine in mice. Furthermore, doxycycline decreased malondialdehyde concentrations in a dose-related manner. Moreover, doxycycline significantly (P < 0.05) prevented the decrease in glutathione, and increased activities of superoxide dismutase and catalase in brain tissues. The results from this study suggest that doxycycline ameliorated schizophrenic-like behaviors via mechanisms related to attenuation of oxidative stress in mouse brain.

Schizophrenia, Antipsychotics, Oxidative Stress, Antioxidant, Doxycycline

Ben-Azu, B. , Omogbiya, I. , Aderibigbe, A. , Umukoro, S. , Ajayi, A. , Eneni, A. and Iwalewa, E. (2016) Doxycycline Ameliorates Schizophrenia-Like Behaviors in Experimental Models in Mice by Targeting Underlying Oxidative Stress. Journal of Behavioral and Brain Science, 6, 539-562. doi: 10.4236/jbbs.2016.613048.