Serotonin 5-HT2A receptors in the CA1 field of the hippocampus mediate head movements in the rabbit.

Rationale: Motor movements (head bobs) in the rabbit have been shown to be elicited by LSD-like hallucinogenic drugs through actions at central serotonin 5-HT2A receptors, though their central locus remains unknown. Serotonergic innervation of the hippocampus has been suggested to play an important role in motor programming including movements of the head. Objectives: We examined whether intrahippocampal in-jections of a 5-HT2A receptor agonist would elicit head bobs and whether elicitation of head bobs would be modified by increases in hippocampal 5-HT2A receptor density. Methods: Animals received bilateral injections of DOI or its vehicle into the dorsal hippocampus either before or after chronic administration of MDL 11,939 or its vehicle. The number of head bobs was counted continuously for 60 min and reported in blocks of 10 min and this was compared with the density of 5-HT2A receptors in dorsal hippocampus. Results: Infusion of DOI into the CA1 region of the dorsal hippocampus elicited head bobs that were blocked by prior intrahippo-campal injection of the 5-HT2A receptor antagonist ketanserin. Receptor autoradiography revealed that chronic administration of MDL 11,939 produced a 2.5-fold up-regulation of 5-HT2A receptors in the CA1 field and dentate gyrus of the hippocampus. This 5-HT2A receptor up-regulation was associated with a nearly 2-fold increase in head bobs elicited by infusion of DOI into the CA1 field. Conclusions: These results indicate that 5-HT2A receptors located in the CA1 field of the hippocampus mediate a motor movement, head bobs, and that this mediation is functionally related to receptor density. [ABSTRACT FROM AUTHOR]