title: Protective effect of adenosine reuptake inhibitors in haloperidol-induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical changes.
abstract: Chronic administration of typical neuroleptics is known to cause persistent oral dyskinesia in rats, an alleged animal model of tardive dyskinesia (TD). The pathophysiology of the syndrome remains unclear. Adenosine is now widely accepted as the major inhibitory neuromodulators in the central nervous system besides gamma-aminobutyric acid. Based on the hypothesis that adenosinergic receptor system may involve in the pathogenesis of TD, we investigated the effect of dipyridamole (5 and 10 mg/kg, i.p.), an adenosine reuptake inhibitor and nimodipine (10 and 20 mg/kg, i.p.) an adenosine transport inhibitor in haloperidol-induced TD by using different behavioural, biochemical and neurochemical parameters in rats. Chronic administration of haloperidol (1 mg/kg, i.p., for 21 days) significantly increased vacuous chewing movements, tongue protrusion, facial jerking which was prevented by adenosine reuptake inhibitors. Chronic administration of haloperidol also resulted in the development of dopamine sensitivity as suggested by increased locomotor activity and stereotypy and decreased % retention time on elevated plus maze paradigm. Pretreatment with adenosine reuptake/transport inhibitors, dipyridamole and nimodipine prevented all these behavioural changes. Chronic administration of haloperidol also resulted in increased oxidative damage in all brain regions which was prevented dose-dependently by both dipyridamole and nimodipine in different brain regions. Chronic administration of haloperidol resulted in decreased turnover of dopamine and norepinephrine in both cortex and subcortical regions which was dose-dependently prevented by adenosine reuptake/transport inhibitors. The major findings of the present study suggested that adenosine reuptake inhibitors dipyridamole and nimodipine could be a possible therapeutic option in neuroleptic induced TD.
authors: Centre with Potential for Excellence in Biomedical Sciences (CPEBS), Panjab University, Chandigarh, India.
authors: Mahendra
authors: M
authors: Bishnoi
authors: Kanwaljit
authors: K
authors: Chopra
authors: Shrinivas K
authors: SK
authors: Kulkarni
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004176:Dipyridamole / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006220:Haloperidol / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009553:Nimodipine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009638:Norepinephrine / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D012153:Retention, Psychology / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D009553:Nimodipine; D004176:Dipyridamole; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D006220:Haloperidol; D004298:Dopamine; D009638:Norepinephrine