EFFECT OF PERINATAL CHANGES IN SEROTONIN METABOLISM ON THE DEVELOPMENT AND BEHAVIOUR OF RAT PUPS

Abstract

Serotonin (5HT) je biogeni amin prisutan u mozgu (središnji odjeljak) i tjelesnim tkivima (periferni odjeljak) gdje ima različite fiziološke uloge. U ovom radu ispitali smo utjecaj perinatalnog povećanja koncentracije serotonina na stopu preživljenja, prirast tjelesne mase i anksiozno ponašanje mladunaca štakora. Životinje smo tretirali od 13.gestacijskog do 21. postnatalnog dana prekursorom serotonina, 5-hidroksitriptofanom (5-HTP) ili inhibitorom razgradnje serotonina, tranilciprominom (TCP). Kontrolnu skupinu tretirali smo fiziološkom otopinom. Obje eksperimentalne skupine su imale znatno smanjenu stopu preživljenja, dok su preživjeli mladunci imali značajno manju masu, kao i njezin prirast, u odnosu na kontrolnu skupinu. Anksiozno ponašanje pratili smo testom ultrazvučnog dozivanja nakon izdvajanja iz legla 13., 16. i 18. postnatalnog dana. Životinje tretirane TCP-om imale su značajno kraće vrijeme latencije do prvog doziva, te znatno veći ukupni broj doziva, broj sljedova doziva i trajanje doziva. U životinja tretiranih 5HTP-om ove su vrijednosti bile slične kontrolnima. U obje eksperimentalne skupine došlo je do kasnijeg prebacivanja frekvencije ultrazvučnog dozivanja s infantilne (40 kHz) na juvenilnu (50 kHz). Rezultati upućuju na to da povišena koncentracija serotonina u doba perinatalnog razvoja negativno djeluje na razvoj mladunaca, povećava razinu anksioznosti i odgađa sazrijevanje mladunaca. Pri tome je učinak TCP-a, koji povisuje koncentraciju 5HT u oba odjeljka, drastičniji od učinka 5-HTP-a koji povisuje koncentraciju 5HT samo u perifernom odjeljku.Serotonin (5HT) is a biogenic amine present both in the brain (central compartment) and in peripheral tissues (peripheral compartment) where it has different physiological functions. In this thesis we have studied the influence of perinatal increase in serotonin concentrations on survival rate, weight gain and anxiety-like behavior in rat pups. The animals were treated with serotonin precursor 5-hydroxytryptophan (5-HTP) or with serotonin catabolism inhibitor tranylcypromine (TCP) from gestational day 13 to post-natal day 21. Control group was treated with saline. Both experimental groups had significantly lower survival rates, while the survived pups had significantly lower body mass and weight gain compared to the control group. Anxiety-like behavior was determined by analyzing ultrasonic vocalization after separation from litter on post-natal days 13, 16 and 18. TCP-treated animals had significantly reduced latency to the first call and significantly higher number of calls, number of call sequences and duration of calls. In animals treated with 5HTP, these values were similar to those of the control group. A delay in frequency transition from infantile (40 kHz) to juvenile (50 kHz) was observed in both experimental groups. The results suggest that exposure to increased serotonin concentrations during perinatal period negatively affects rat development, increases the level of anxiety and delays maturation. The effect of TCP, which raises serotonin level in both 5HT compartments, is more drastic than the effect of 5HTP, which raises serotonin concentration only in the peripheral compartment