Bio-behavioural studies into the antidepressant and antipsychotic-like effects of Garcinia mangostana Linn extract and alpha-mangostin as adjunctive-or mono-therapy in a rodent model of schizophrenia

Abstract

Introduction: Garcinia mangostana Linn (GML) or mangosteen has anti-inflammatory, antioxidant and neuroprotective actions. Its bioactive constituents, α- , β- , and γ- mangostin also inhibit cAMP phosphodiesterase and 5-HT2A receptors. Disorganized redox- inflammatory cascades characterize schizophrenia, with antioxi-dant/anti-inflammatory agents representing novel treatments. GML extract and α- mangostin were assessed as stand-alone or adjunc-tive treatment with haloperidol vs. haloperidol alone in a prenatal immune-inflammatory model (PII) of schizophrenia.Methods: Sprague Dawley dams received lipopolysaccharide (100 μg/kg; gestational days 15 and 16). Male offspring received vehicle, haloperidol (2 mg/kg), GML extract (50 mg/kg), haloperidol+GML, α- mangostin (20 mg/kg) and haloperidol+α- mangostin from post-natal days 52–66. Control dams and control offspring received ve-hicle. Sensorimotor gating, social interaction, locomotor activity and depressive-like behaviour were assessed on postnatal days 64–65. Frontal-cortical lipid peroxidation and plasma interleukin-1 (IL-1) and tumour necrosis factor-α (TNF-α) were assayed post-mortem.Results: PII reduced sensorimotor gating, induced depressive be-haviour and increased locomotor activity and social behaviour in off-spring, elevated cortico-striatal lipid peroxidation and increased plasma IL- 6/TNF-α levels. Sensorimotor gating deficits were re-versed by haloperidol and haloperidol+GML. α- Mangostin reversed locomotor hyperactivity, with α- mangostin, GML and haloperidol combinations reversing depressive-like behaviour. Haloperidol was an ineffective antidepressant. Social deficits were reversed by haloperidol+GML. Haloperidol and α- mangostin reversed elevated cortical lipid peroxidation, with elevated plasma IL-6/TNF-α reversed by GML, α- mangostin, haloperidol and haloperidol combinations.Conclusions: Schizophrenia-like bio-behavioural changes are varia-bly responsive to haloperidol, GML and α- mangostin. Depressive- like behaviours are more responsive to GML, α- mangostin or combina-tions with haloperidol. By targeting redox-inflammatory processes, GML may be a useful adjunctive treatment in schizophrenia