Increase in serotonin-1A receptor responsiveness following haloperidol, withrawal

ABSTRACT

In view of a role of 5-hydroxtryptamine [serotonin; 5-HT]-1A receptors in the elicitation of extrapyramidal symptoms [EPS], The present study was designed to monitor pre- and postsynaptic responses to a selective 5 HT-1A ligand, 8-hydroxy-2- [di-n-propylamino] tetralin [8-OH-DPAT] following single and repeated [two times a day for 9 days] administration of haloperidol [5 mg/kg] in rats. The intensity of 5 H-T syndrome elicited by 8-OH-DPAT [0.5 mg/kg] was taken as measure of postsynaptic response. 8-OH-DPAT induced decreases of 5-HT metabolism in the striatum and brain were taken as a measure of postsynaptic response. 8-OH-DPAT induced forepaw treading and hyperlocomotion were smaller in haloperidol than saline injected rats. The decreases were not observed following withdrawal from repeated administration of haloperidol. Flat body posture not altered by single injection of haloperidol was enhanced following withdrawal from repeated administration of haloperidol. Haloperidol plus 8OH-DPAT injected animals exhibited comparable levels of 5-HT metabolism in the striatum as well as in the brain. Administration of 8-OH-DPAT significantly decreased 5-HT metabolism in brain but not in striatum of repeated saline injected animals. Conversely, same dose of 8-OH-DPAT injected to haloperidol-injected animals did not decrease 5-HT metabolism in the brain but decreased it in the striatum. The results show an increase in the responsiveness of pre-and postsynaptic 5-HT-responsiveness of post and presynaptic 5-HT-1A receptors may be involved in the greater incidence of EPS in patients treated with neuroleptics such as haloperidol