Perinatal asphyxia induces long-term changes in dopamine D1, D2, and D3 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 D1, D2, and D3 receptors (analyzed by quantitative autoradiography) in the mesotelencephalic dopamine systems of the 4-week-old rat. Perinatal asphyxia reduced D1 antagonist binding ([3H]SCH 23390 in the presence of ketanserine) in the accumbens nucleus, the olfactory tubercle, and the substantia nigra and increased D1 agonist binding ([3H]dopamine in the presence of spiperone) in the accumbens nucleus and the olfactory tubercle. No changes in D2 antagonist binding ([123]iodosulpride) were found, whereas D2 agonist binding ([3H]N-propylnorapomorphine, [3H]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. D3 agonist binding (R/S-(+/-)-2-(N,N-di[2,3(n)-3H] propylamino)-7-hydroxy-1,2,3,4-tetrahydronaphthalene, [3H]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 D1 receptors and increased D1 agonist affinity in the accumbens nucleus and the olfactory tubercle and reduced the number of D1 receptors in the substantia nigra. The number of D2 receptors was unchanged by asphyxia, whereas the D2 agonist affinity was reduced in the caudate-putamen and in the accumbens nucleus. D3 agonist binding was increased in the caudate-putamen selectively following 15-16 min of asphyxia. In conclusion, asphyxia during birth induces long-term changes in the binding characteristics of dopamine receptors in the mesotelencephalic dopamine systems, which may contribute to previously reported behavioral changes.