Alpha-phenyl-N-tert-butylnitrone prevents oxidative stress in a haloperidol-induced animal model of tardive dyskinesia: investigating the behavioural and biochemical changes

Haloperidol (HP) is a widely prescribed antipsychotic drug used for the treatment of mental disorders. However, while providing therapeutic benefits, this drug also causes serious extrapyramidal side effects, such as tardive dyskinesia (TD). Upon chronic administration, HP causes behavioural supersensitivity to dopamine D2 receptor agonists, as well as the development of vacuous chewing movements (VCMs), in an animal model of human TD. Currently, a prevailing hypothesis to account for these behavioural abnormalities implicates oxidative stress. This study was undertaken to examine whether the free radical trapping agent, α-phenyl-N-tert-butylnitrone (PBN), can prevent the development of behavioural supersensitivity to dopamine D2 receptor agonists and the development of VCMs. Additionally, the study examined whether increased synthesis of apoptosis inducing factor (AIF) can result from HP-induced oxidative stress. Male Sprague-Dawley rats were treated with HP in conjunction with PBN, or its vehicle, for 4weeks. After a 24-hour washout period, behavioural observations were recorded along with the estimation of lipid peroxidation and antioxidant enzyme activities. The free radical trapping agent, PBN, prevented the development of...Continue Reading