EFFECTS OF PERINATAL ASPHYXIA ON THE MESOSTRIATAL MESOLIMBIC DOPAMINESYSTEM OF NEONATAL AND 4-WEEK-OLD MALE-RATS/

The present study was undertaken in order to study the effects of peri natal asphyxia on tyrosine hydroxylase (TH) activity, dopamine levels and turnover, and dopamine metabolites (3,4-dihydroxyphenylacetic acid , DOPAC, homovanillic acid, HVA, and 3-methoxytyramine, 3-MT, analyzed by high-performance liquid chromatography, HPLC) measured in the basa l ganglia of the 20- to 40-min-old newborn and it-week-old male rat, A sphyxia was induced in pups by placing the fetuses, still in their ute rus horns removed by hysterectomy from pregnant rats at full term, in a 37 degrees C water bath for 15-16 min or 19-20 min, Following asphyx ia, the uterus horns were opened, and the pups were removed and stimul ated to breathe, A 100% and 50-80% pup survival was obtained following 15-16 min and 19-20 min of asphyxia, respectively. Acute changes were studied in brains from newborn pups 20-40 min after delivery, and lon g-term changes were studied in brains from 4-week-old rats. No changes in TH-activity could be observed in the substantia nigra/ventral tegm ental area (SN/VTA), the striatum, or the accumbens nucleus/olfactory tubercle (ACC/TUB), in the newborn or the 4-week-old rat. In the newbo rn rat, 19-20 min of asphyxia increased (as compared to controls) dopa mine levels in the SN/VTA to 136+/-14% and in the ACC/TUB to 160+/-10% , indicating an increased synthesis and/or release of dopamine. DO-PAC levels were increased in the SN/VTA to 150+/-14% and in the ACC/TUB t o 151+/-10%, and HVA levels were increased to 152+/-16% in the striatu m and to 117+/-4% in the ACC/TUB. Following 15-16 min of asphyxia, dop amine levels were increased to 130+/-12% in the ACC/TUB, and DOPAC lev els were increased to 135+/-6% and 130+/-12% in the SN/VTA and the ACC /TUB, respectively. This suggests that the increased dopamine levels m ay preferably reflect an increased release of dopamine following perin atal asphyxia. In the 4-week-old rat, dopamine levels were decreased i n the SN/VTA to 71+/-4%, in the striatum to 52+/-8%, and in the ACC/TU B to 53+/-7%, following 19-20 min of perinatal asphyxia as compared to controls. No changes were observed in DOPAC, HVA, or 3-MT levels, ind icating that the reduced dopamine levels reflect a reduced dopamine sy nthesis following perinatal asphyxia. A decrease in dopamine utilizati on was observed in the striatum to 15+/-8% and in the ACC/TUB to 9+/-1 3% following 19-20 min of perinatal asphyxia as compared to controls. This indicates that perinatal asphyxia produced long-lasting reduction s in activity in the mesostriatal/mesolimbic dopamine systems in the 4 -week-old rat.