Impaired striatal dopamine receptor development: differential D-1 regulation in adults.
Previous reports have indicated that prenatal, but not postnatal, haloperidol impairs the ontogenic development of striatal dopamine D-2 receptors. In the present study a specific D-2 receptor antagonist, spiroperidol (1.0 mg/kg i.p.) and/or a specific D-1 receptor antagonist, SCH 23390 (0.30 mg/kg i.p.), was administered to rats for 32 successive days from birth. Postnatal spiroperidol and SCH 23390 treatments markedly impaired the development of striatal dopamine D-2 and D-1 receptors, respectively, at 12 weeks after birth. Spiroperidol did not affect D-1 receptor development and did not modify the effect of SCH 23390 treatment. Also, SCH 23390 did not affect D-2 receptor development and did not modify the effect of spiroperidol treatment. When rats with impaired development of striatal D-2 receptors were challenged at 12 weeks with spiroperidol (1.0 mg/kg per day i.p. x 17 days) D-2 receptors did not up-regulate. However, when rats with impaired development of striatal D-1 receptors were challenged at 12 weeks with SCH 23390 (0.30 mg/kg per day i.p. x 17 days) D-1 receptors did up-regulate. These findings demonstrate that postnatal treatment with D-1 and D-2 receptor antagonists can permanently impair the development of striatal D-1 and D-2 receptors. Moreover, the ability of developmentally impaired striatal D-1 receptors to up-regulate in adulthood appears to be greater than that for the developmentally impaired striatal D-2 receptors.
Saleh
M I
MI
Department of Pharmacology, Quillen-Dishner College of Medicine, East Tennessee State University, Johnson City 37614.
Kostrzewa
R M
RM
D000818:Animals; D000831:Animals, Newborn; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D013134:Spiperone / Q000494:pharmacology
D001552:Benzazepines; D011954:Receptors, Dopamine; D013134:Spiperone