Perinatal asphyxia induces long-term changes in dopamine D-1, D-2, and D-3 receptor binding in the rat brain

We have investigated the long-term effects of 15-16 min or 19-20 min of perinatal asphyxia on D-1, D-2, and D-3 receptors (analyzed by quantitative autoradiography) in the mesotelencephalic dopamine systems of the 8-week-old rat. Perinatal asphyxia reduced D-1 antagonist binding ([H-3]SCH 23390 in the presence of ketanserine) in the accumbens nucleus, the olfactory tubercle, and the substantia nigra and increased D-1 agonist binding ([H-3]dopamine in the presence of spiperone) in the accumbens nucleus and the olfactory tubercle. No changes in D-2 antagonist binding ([I-125]iodosulpride) were found, whereas D-2 agonist binding ([H-3]N-propylnorapomorphine, [H-3]NPA) was reduced in the posterior part of the caudate-putamen, and following 19-20 min of asphyxia it was also reduced in the accumbens nucleus. D-3 agonist binding (R/S-(+/-)-2-(N,N-di[2,3(n)-H-3]propylamino)-7-hydroxy-1,2,3,4-tetrahydronaphthalene, [H-3]7-OH-DPAT) was increased in the anterior part of the caudate-putamen following 15-16 min but not 19-20 min of asphyxia. The results indicate that perinatal asphyxia reduced the number of D-1 receptors and increased D-1 agonist affinity in the accumbens nucleus and the olfactory tubercle and reduced the number of D-1 receptors in the substantia nigra. The number of D-2 receptors was unchanged by asphyxia, whereas the D-2 agonist affinity was reduced in the caudate-putamen and in the accumbens nucleus. D-3 agonist binding was increased in the caudate-putamen selectively following 15-16 min of asphyxia. In conclusion asphyxia during birth induces longterm changes in the binding characteristics of dopamine receptors in the mesotelencephalic dopamine systems, which may contribute to previously reported behavioral changes. (C) 1997 Academic Press.