RELATIONSHIPS BETWEEN MIDEMBRYONIC 5-HT2 AGONIST AND OR ANTAGONIST EXPOSURE AND DETOUR LEARNING BY CHICKENS/

The importance of serotonin (5-HT) as both a transmitter and a regulat ory signal during development of many species is well established. The availability of 5-HT receptor subtype agonists and antagonists will e nable pharmacological dissection of the importance of one or more of t he 5-HT receptors for their involvement in the mediation of developmen tal insults by drugs that are less selective but include actions upon serotonergic function. Such insults include exposure to cocaine or opi ate withdrawal, both of which are blocked or attenuated by 5-HT2 antag onists. The 5-HT2 receptor agonist dimethoxyiodophenylaminopropane (DO I),like cocaine, causes vasoconstriction during embryogenesis, herniat ed umbilici in hatchlings, and altered detour learning by young chicke ns after injection into eggs at late stages of embryogenesis. The 5-HT 2 antagonist ritanserin (RIT) blocks or significantly attenuates these effects. This study describes an effect of DOI on posthatch detour le arning when injected earlier during embryogenesis (i.e., on embryonic day 12, E12) which is opposite its effect when injected later (i.e., o n E15). Both effects are blocked by an inactive dose of RIT (0.3 mg/kg egg) and by a higher dose of RIT (0.9 mg/kg egg), which itself retard s posthatch detour learning following E12 injection. Thus, excessive s timulation or blockade of 5-HT2 receptors around midembryogenesis can cause a similar behavioral teratogenic outcome. The data are discussed in relation to the likelihood that potential use of 5-HT2 antagonists for treating pregnant women and their fetuses who are not at risk is nil. (C) 1998 Elsevier Science Inc.