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 o f perinatal asphyxia on D-1, D-2, and D-3 receptors (analyzed by quant itative 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 nucle us, the olfactory tubercle, and the substantia nigra and increased D-1 agonist binding ([H-3]dopamine in the presence of spiperone) in the a ccumbens nucleus and the olfactory tubercle. No changes in D-2 antagon ist binding ([I-125]iodosulpride) were found, whereas D-2 agonist bind ing ([H-3]N-propylnorapomorphine, [H-3]NPA) was reduced in the posteri or part of the caudate-putamen, and following 19-20 min of asphyxia it was also reduced in the accumbens nucleus. D-3 agonist binding pylami no)-7-hydroxy-1,2,3,4-tetrahydronaphthalene, [H-3]7-OH-DPAT) was incre ased in the anterior part of the caudate-putamen following 15-16 min b ut not 19-20 min of asphyxia. The results indicate that perinatal asph yxia reduced the number of D-1 receptors and increased D-1 agonist aff inity 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 follo wing 15-16 min of asphyxia. In conclusion asphyxia during birth induce s longterm changes in the binding characteristics of dopamine receptor s in the mesotelencephalic dopamine systems, which may contribute to p reviously reported behavioral changes. (C) 1997 Academic Press.