Role of central 5-HT2 receptors in mediating head bobs and body shakes in the rabbit

Systemic administration of the 5-HT(2A/2C) agonist DOI [(1(2,5-dimethoxy-4-iodophenyl)-2-aminopropane)hydrochloride] in rabbits elicits head bobs and body shakes, which are mediated by 5-HT(2A) and 5-HT(2C) receptors, respectively. This study was designed to determine whether the receptors mediating these behaviors are primarily located in the brain or in the periphery. Systemic administration of the peripheral 5-HT(2A/2C) antagonist xylamidine 30 min before systemic DOI challenge attenuated DOI-elicited body shakes by 50% without an effect on head bobs, suggesting a central origin for head bobs and a partial peripheral and a partial central origin for body shakes. Central administration of DOI into the lateral ventricle (ICV) elicited head bobs but not body shakes, demonstrating that the receptors mediating head bobs are centrally located. Pretreatment with ICV xylamidine blocked head bobs elicited by ICV DOI, indicating that the lack of inhibition, when systemically administered, is due to xylamidine's failure to reach central receptors. ICV pretreatment with the 5-HT(2A) receptor antagonist ketanserin inhibited ICV DOI-elicited head bobs establishing that 5-HT(2A) receptors activation elicits head bobs. In conclusion, 5-HT(2A) receptors mediating head movements are located in the brain whereas 5-HT(2C) receptors mediating the body movements appear to be located at different central sites as well as in the periphery.