Neuroprotective Effects of Combined Omega-3 Fatty Acids and Vitamin E on Haloperidol-Induced Cerebellar Alterations in Rats

 Alake Tomiwa Goodness¹, Samson Oluwamuyiwa Alade¹, Joshua Aduragbemi Ajao², Akinsanmi Festus Akinsehinwa¹, Opeyemi Ojo Famuyide¹, Olakunle James Onaolapo³, Adejoke Yetunde Onaolapo⁴

1. Department of Anatomy, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria 
2. Department of Pharmacology and Therapeutics, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria 
3. Behavioural Neuroscience and Neuropharmacology Unit, Department of Pharmacology and Therapeutics, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria, ORCID: 0000-​0003-2142-6046 ojonaolapo@lautech.edu.ng  
4. Behavioural Neuroscience and Neurobiology Unit, Department of Anatomy, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria, ORCID: 0000-0001-7126-7050, ayonaolapo@lautech.edu.ng 

ABSTRACT 

Haloperidol, a typical antipsychotic widely used in the management of schizophrenia, is associated with neurotoxic
effects mediated through oxidative stress and neuronal disruption. Omega-3 fatty acids, known for their anti-inflammatory and neuroprotective properties, and vitamin E, a potent lipid-soluble antioxidant, have individually
demonstrated the capacity to attenuate oxidative damage. However, their combined protective effects against haloperidol-induced cerebellar toxicity remain insufficiently investigated. This study examined the neuroprotective
potential of co-administered omega-3 fatty acids and vitamin E on haloperidol-induced behavioural, biochemical, and histological alterations in the rat cerebellum. Sixty male Wistar rats (80–100 g) were randomly assigned to
six groups (n = 10). Group A (control) received a standard diet and olive oil; Group B received omega-3 fatty acids (500 mg/kg of feed) and vitamin E (10 IU/kg, oral). Group C received haloperidol (1 mg/kg, intraperitoneally). Groups
D and E were administered haloperidol together with omega-3 fatty acids or vitamin E, respectively, while Group F received haloperidol with both agents for 28 days. Haloperidol treatment (Group C) resulted in significant reductions
(p < 0.05) in body weight, feed intake, locomotion, rearing, and spatial working memory when compared with the control. Grooming behaviour and catalepsy scores were markedly elevated in Group C but significantly reduced in Groups D–F. Haloperidol also increased malondialdehyde (MDA), IL-1β, IL-6, and TNF-α levels while reducing total antioxidant capacity; these alterations were reversed following co-treatment with omega-3 fatty acids and vitamin E.
Histological examination revealed pronounced cerebellar degeneration in the haloperidol-only group, whereas neuronal architecture was largely preserved in Groups D–F. Overall, the findings demonstrate that combined administration of omega-3 fatty acids and vitamin E provides significant neuroprotection against haloperidol-induced cerebellar toxicity and catalepsy, highlighting their potential as adjunct therapies in mitigating antipsychotic-related
neurodegeneration. 

KEYWORDS: Antioxidant, Neurotoxicity, Neuroinflammation, Neuroprotection, Oxidative stress.