Prenatal manipulation of the serotonergic system: Biochemical, pharmacological and behavioral effects

Rat pups were exposed in utero to pharmacological agents that stimulated or diminished serotonergic activity in vivo. Dams received 5-Methoxytryptamine 1mg/kg, from day 12 of gestation to birth, or parachlorophenylalanine, the serotonin synthesis inhibitor, from day 7 to 17 of gestation. Both groups of offspring showed significant reductions in the specific high affinity uptake of 3H-5-HT into brainstem and forebrain areas on postnatal days 1, 15, and 30, indicating reduced outgrowth of serotonin. At 15 days of age, both groups of treated offspring showed deficits in activity and in performing behaviors that required inhibition, but these deficits were no longer apparent on Day 30. Dose response experiments for 5-MT produced a dual effect: enhanced uptake in forebrain and inhibition of uptake in brainstem and forebrain on postnatal days 1, 15 and 30. Prenatal 5-MT caused deficits in avoidance and activity. Prenatal exposure to PAT, the 5-HT1a agonist caused reduced uptake in brainstem, while exposure to TFMPP (the 5-HT1b agonist) produced enhanced uptake in forebrain, as did the high dose of 5-MT. Sensitivity of the pharmacological response to acute 5-MT, 1 mg/kg, and apomorphine, 5 mg/kg was measured in an activity test