Behavioral effects of 8-OH-DPAT in single and repeated haloperidol injected rats

Haloperidol is an antipsychotic drug and shown to be antagonist at D2 receptors and found to cause severe impairment of locomotor performance. The serotonin (5HT1A) receptor agonist 8-OH-DPAT has been reported to attenuate extrapyramidal side effects of haloperidol. The present study was designed to examine the modulatory effect of serotonergic activities on haloperidol induced up-regulation of dopamine D2 receptors. In the acute phase of study, 8-OH-DPAT (0.5 mg/kg/ml) elicited behavioral syndrome was monitored in rats preinjected with haloperidol(5 mg/kg/ml). Results of single haloperidol administration revealed that 8-OH-DPAT induced forepaw treading (p < 0.05) and hyperlocomotion (p < 0.01) were smaller in haloperidol than saline preinjected rats. In repeated phase of study, 8-OH-DPAT (0.5 mg/kg/ml) induced behavioral syndrome was monitored in rats injected with haloperidol for 10 days (x2). The result of repeated haloperidol administration showed that 8-OH-DPAT elicited flat body posture (p < 0.01) was greater in repeated haloperidol injected rats than repeatedly saline injected rats. Relationship between 5HT1A receptors and D2 receptors has been discussed. It is suggested that combining neuroleptics with 5HT1A ligands is thought to improve the preclinical profile of neuroleptics and may be of interest in the development of new compounds that have greater therapeutic potential and/or better tolerated.