SEROTONIN1A RECEPTOR AGONISM IN THE EXPRESSION OF BEHAVIORAL DOPAMINERGIC SUPERSENSITIVITY IN SUBCHRONIC HALOPERIDOL TREATED RATS

The idea that serotonin (5-hydroxytryptamine; 5-ht) is contributed in schizophrenia has long been advocated and alterations in 5-ht neurotransmission has been hypothesized to modulate both the therapeutic and extrapyramidal symptoms (eps) liability of conventional neuroleptics. the 8-hydroxy-2-(di-n- propylamino) tetralin (8-oh-dpat), a preferential 5-ht1a ligand, has been reported to attenuate eps functions of haloperidol in animals. in view of a possible role of 5-ht1a receptors in the management of eps functions of a neuroleptic drug, the present study was designed to investigate behavioral responses of 8-oh-dpat at a challenge dose of 0.5mg/kg in rats with subchronic haloperidol administration at a dose of 5mg/kg twice daily for 5 days. the intensity of 5-ht syndrome provoked by 8-oh-dpat was taken as a measure of postsynaptic responses. in the present study administration of haloperidol at a dose of 5mg/kg twice daily for 5 days decreased locomotion significantly (p<0.01) in familiar (home cage) environment. subchronic administration of haloperidol at the same dose elicited significant (p<0.01) cataleptic responses in rats when compared with saline treated rats. results revealed that 8-oh-dpat-induced hyperlocomotion (p<0.05) and forepaw treading (p<0.1) were significantly smaller in rats pre-treated with haloperidol for 5 days than repeatedly saline injected rats. conversely, the other components of the syndrome i.e. flat body posture (p<0.001), hind limb abduction (p<0.001) and straub tail (p<0.01) were significantly greater in repeated haloperidol treated rats when compared with repeated saline injected rats. these findings help to demonstrate a causal link between the upregulation of da-d2 receptors and the decrease in the effectiveness of presynaptic 5-ht1a receptors following subchronic haloperidol administration and this may further help to yield an antipsychotic agent with an improved profile of efficacy to eps, thereby widening its therapeutic window.