Protective effects of histamine H3-receptor ligands in schizophrenic behaviors in experimental models

Mahmood Danish, Khanam Razia, Pillai Krishna Kolappa, Akhtar Mohd

Index: Pharmacol. Rep. 64(1) , 191-204, (2012)

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Abstract

Schizophrenia (SCZ) afflicts around 1% of the world’s population with characteristic symptoms such as hallucinations, delusions, and cognitive disorders. Several experimental studies in the past have indicted brain histaminergic neuronal system involvement in the pathogenesis of psychotic disorders including SCZ. Present study investigates anti-schizophrenic activity using two histamine H3-receptor (H3R)-antagonists/inverse agonists, ciproxifan (3.0mg/kg, ip) and clobenpropit (15mg/kg, ip), on some of the established animal model of schizophrenia, for example, amphetamine (AMPH) and dizocilpine (MK-801)-induced hyperactivity, apo-morphine (APO)-induced climbing behavior, scopolamine and MK-801-induced learning and memory deficits and haloperidol-induced catalepsy including determination of acetylcholinesterase (AChE) activity. Results of the present study demonstrate that ciproxifan and clobenpropit were able to control AMPH and MK-801-induced hyperlocomotor activities demonstrated as reduced horizontal activity and reduced number of movements made by rats. Further, there was overall reduction in APO-induced climbing behavior. Learning and memory deficits, as evaluated on elevated plus maze, followed by estimation of brain AChE activity demonstrated positive results with these protypical imidazole H3R-antagonists/inverse agonists. In conclusion, present study demonstrates anti-schizophrenic like activities of ciproxifan and clobenpropit and supports the therapeutic interest of histamine H3R antagonists/inverse agonists to improve symptomatic treatment of psychotic disorders.