Serotonin receptor ontogeny: effects of agonists in 1-day-old rats.

Although numerous subtypes of serotonin [5-hydroxytryptamine (5-HT)] receptors have been identified in the newborn rat by radioligand binding studies, there have been few studies of the functional significance of these early receptors, most without the benefit of selective drugs. We performed acute dose-response and time course behavioral studies in 1-day-old rats with the putative selective agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (5-HT1A), 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H-indole (RU 24969) (5-HT1B), and (+-)1-(2,5-dimethoxy-4-iodo-phenyl aminopropane)-2 (DOI) (5-HT2/1C). The agonists induced distinctive behavioral syndromes. The DOI syndrome mainly included rudiments of forepaw myoclonus and dystonic limb postures, but no shaking behavior (head shakes or wet-dog shakes) or spinal myoclonus, two key reference behaviors for its effects in adult rats. The most distinctive feature of the 8-OH-DPAT-induced syndrome was flat body posture. RU 24969 most significantly increased locomotor activity, inducing propulsive movements with episodic rests and sudden hindlimb jerks. These studies suggest that functional and differential activity of 5-HT1A, 5-HT1B, and 5-HT2/1C receptors occurs much earlier in the rat than previously appreciated. The absence of DOI-induced shaking behavior and spinal myoclonus, however, suggests incomplete maturation at the level of the receptor or effector pathways for these behaviors.