Cortical 5‐HT2A receptor density predicts 5‐HT2A receptor mediated behavior in the rabbit

Serotonin 5‐HT 2 receptor agonists such as DOI [1(2, 5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane] injected systemically or directly into frontal cortex, elicit stereotyped head movements that are mediated by 5‐HT 2A receptors. Chronic administration of 5‐HT 2A receptor antagonists, can produce either a down‐regulation, e.g., BOL (d‐2‐bromolysergic acid diethylamide) or an up‐regulation (MDL11,939) of cortical 5‐HT 2A receptors in the rabbit with no change in the density of the 5‐HT 2C receptor. We examined the degree to which the time course for the onset and offset of changes in cortical 5‐HT 2A receptor density was correlated with functional changes as measured by the magnitude of DOI elicited, 5‐HT 2A mediated, head movements (head bobs). First, the magnitude of DOI elicited head bobs was measured at 1–8 days after chronic BOL (5.8 μmol/kg), MDL11,939 (10 μmol/kg) or vehicle administration. Second, rabbits were injected with BOL, MDL11,939 or vehicle once daily for 8 days and then, 1–8 days after the last drug or vehicle injection, DOI elicited head bobs were determined. Samples of frontal cortex were obtained for each animal immediately following behavioral testing, and 5‐HT 2A receptor density was measured using [ 3 H]ketanserin. Thus, each animal provided a value for receptor density and number of head bobs and these two measures showed a high degree of correlation between of 0.94 for BOL and 0.95 for MDL11,939. This study establishes that the density of 5‐HT 2A receptors in cortex reflects their functional status. Supported by NIMH Grant MH16841‐38 (JAH).