EFFECTS OF A NOVEL TRYPTOPHAN HYDROXYLASE INHIBITOR PARA-ETHYNLPHENYLALANINE ON SURVIVAL AND GROWTH RATES IN MICE
Open Access
- Author:
- Ramos, Daniel Jose
- Area of Honors:
- Veterinary and Biomedical Sciences
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Dr. Anne Milasincic Andrews, Ph D, Thesis Supervisor
Dr. Anne Milasincic Andrews, Ph D, Thesis Supervisor
Dr. Lester C Griel Jr., Thesis Honors Advisor - Keywords:
- Tryptophan hydroxylase
Para-Ethynlphenylalanine - Abstract:
- This study aims to investigate the effects of the novel tryptophan hydroxylase inhibitor, p- ethynylphenylalanine (pEPA) in mice specifically during the early postnatal period. A pilot study was carried out comparing pEPA with p- chlorophenylalanine (pCPA), which has been used previously in adult and postnatal rats and adult mice to deplete brain serotonin levels. We compared the effects of postnatal administration of pEPA vs. pCPA on growth rates and survival in two different strains of mice. Daily injections of 1 or 10 mg/kg pEPA, 50 or 100 mg/kg pCPA, or saline were administered during postnatal days 4 to 21 (P4-P21) to C57BL/6J and CD-1 mice. Pup weights were measured on P5-21 to measure early postnatal growth. Survival rates at P21 were evaluated. Brain regions including frontal cortex, hippocampus, striatum, brain stem, and hypothalamus were collected at P21 for future analysis of serotonin levels to evaluate the extent of synthesis inhibition. The current results indicate that postnatal administration of the higher 100 mg/kg pCPA dose resulted in significantly lower P21 weights in both sexes and strains of mice. The higher 10 mg/kg pEPA dose was also associated with lower P21 weights in both sexes of CD-1 mice. The CD-1 strain showed 100% survival in all cases, whereas mortality occurred across most treatment groups in the C57BL/6J strain. Based on postnatal growth and survival, CD-1 mice showed greater tolerability of these drugs and in particular, the lower 1 mg/kg dose of pEPA and both doses of pCPA. Final conclusions regarding drug, dose, and mouse strain for use in future studies will be made on the basis of these findings, in conjunction with results on the extent and selectivity of brain serotonin depletions.