PERINATAL TREATMENT of rats with MAO inhibitor tranylcypromine

Serotonin (5-hydroxytryptamine, 5HT) regulates the development of 5HT neurons and target tissues during neurogenesis, while later it assumes the function of a neurotransmitter. Alterations in serotonin neurotransmission are indicated as biological substrates in several neuropsychiatric disorders, including autism. The most consistent 5HT-related finding in autistic disorder is hyperserotonemia, but the mechanism of its development and its relation to central 5HT dysfunction are still unclear. In an attempt to pharmacologically induce hyperserotonemia during the period of most intensive development of 5HT neurons, and to later investigate its effects on central 5HT functions, we have treated rats from gestational day 13 until postnatal day 21 with 2 mg/kg of the nonselective irreversible MAO inhibitor tranylcypromine (TCP). The control group received saline in the same manner. TCP treated rats displayed a long-lasting significant increase in platelet 5HT concentrations compared to the control rats. The TCP treated group had smaller litters, significantly lower pup survival rate, and slower weight gain during the post-weaning free-feeding period than the control group. Pups from the TCP group returned to their dams significantly slower than the control pups suggesting lower separation anxiety. Our results indicate that the perinatal treatment of rats with tranylcypromine has induced both, disregulation of the peripheral 5HT homeostasis and disturbances in central 5HT physiology in pups and young rats. The extent of the changes in the central serotonergic compartment in adult rats will be explored in our further studies.