Publication:

Preventive effects of geraniol in schizophrenia-like symptoms in mice models of psychosis

Background The pathogenesis of schizophrenia has been linked to N-methyl-D-aspartate receptor (NMDAr) inhibition and DAr hyperfunction. Geraniol is a naturally occurring acyclic monoterpene with diverse pharmacological applications. We aimed to assess the effect of geraniol on schizophrenia-like symptoms, vis a vis its modulatory actions on neurochemicals in mice models of psychosis.

Methods In acute studies, male Swiss mice (n=5/group) were intraperitoneally treated with geraniol (25, 50 and 100 mg/kg), risperidone (0.5 mg/kg) or vehicle (10 ml/kg) prior to ketamine (KET) (10 mg/kg)-induced stereotypy and hyperlocomotion. In the chronic studies, mice (n=7/group) were exposed to 14 days interventions (geraniol or risperidone) following a preventive treatment with KET (20 mg/kg) from days 7-14 consecutively. The effects of treatments (e.g., geraniol or risperidone) alone and on KET-induced schizophrenia-like symptoms were investigated on the last day, 24 hours after treatments. Following that, neurochemical and neurotrophic alterations in the brain (striatum, prefrontal cortex, and hippocampus) tissues were investigated.

Results Intoxication with KET was associated with schizophrenia-like symptoms as evidenced by stereotypy behavior and hyperlocomotion. KET further induced hyperlocomotion, behavioral despair, and cognitive impairment in the chronic studies. It altered the levels of dopamine, 5-hydroxytrypamine, glutamic acid decarboxylase (GAD), acetylcholinesterase (AChE), and brain-derived neurotrophic factor (BDNF) in brain tissues. However, GER (50 and 100 mg/kg) administration significantly prevented the brain's insults caused by KET.

Conclusions Altogether, the findings support geraniol's neuroprotective activity while also adding to the body of knowledge that geraniol inhibits schizophrenia-like symptoms via modulation of neurochemical and neurotrophic pathways.