The Influence of 2,4-Diamino-6-Hydroxypyrimidine and Food Restriction on Tetrahydrobiopterin Metabolism, Neurotransmitters and Behaviour in the Rat

Abstract

Administration of 2,4-diamino-6-hydroxypyrimidine (DAHP) in the diet of rats reduced total biopterins in plasma, brain and liver. The levels of dihydropteridine reductase (DHPR) and the rate of biopterin biosynthesis were unaffected. Animals on the DAHP diet consistently lost weight and ate less. Hence, the effects of DAHP and food restriction on biopterin metabolism, neurotransmitters and behaviour were investigated. Food restriction had similar effects to DAHP in that brain, liver and plasma biopterins were reduced. Neither DAHP nor food restriction significantly influenced the levels of neurotransmitters in the brain. However, DAHP reduced general activity and rearing of the animals in an open field arena while food restriction increased these parameters. These results suggest that the behavioural changes are either due to neurotransmitter changes not revealed by gross brain neurochemical analyses or to a more direct effect of tetrahydrobiopterin. In addition, the effects of DAHP may be confounded to some degree with these of reduced dietary intake and this has implications for the use of DAHP as an animal model of tetrahydrobiopterin (BH4) deficiency.