MIF-1 attenuates spiroperidol alteration of striatal dopamine D2 receptor ontogeny.
Long-term postnatal treatment of rats with the dopamine D2 receptor antagonist, spiroperidol, results in the impaired development of striatal D2 receptors. Because the tripeptide prolyl-leucyl-glycinamide (MIF-1) attenuates haloperidol-induced up-regulation of striatal dopamine D2 receptors in adult rats, we studied the effect of MIF-1 on the spiroperidol-induced alteration of striatal D2 ontogeny. Postnatal treatment of rats with spiroperidol (1.0 mg/kg/day, IP, x32 days from birth) resulted in a 74% decrease in the Bmax for [3H]spiroperidol binding with no change in the Kd at 5 weeks. When rats were studied at 8 weeks, in the absence of additional treatment, total specific [3H]spiroperidol binding was reduced by 59%. While MIF-1 alone (1.0 mg/kg/day, IP, x32 days from birth) had no effect on [3H]spiroperidol binding, MIF-1 completely attenuated the ontogenic impairment of striatal D2 receptors that was produced by spiroperidol treatment. At 5 weeks the Bmax for [3H]spiroperidol binding was at the saline control level in the group of rats cotreated with spiroperidol and MIF-1. At 8 weeks, with no additional treatments, the specific binding of [3H]spiroperidol to striatum was also at control levels in the group cotreated with spiroperidol and MIF-1. These findings demonstrate that MIF-1 attenuates spiroperidol-induced impairment of development of striatal dopamine D2 receptors in rats.
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; D003342:Corpus Striatum / Q000378:metabolism*; D007700:Kinetics; D009075:MSH Release-Inhibiting Hormone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000096:biosynthesis* / Q000187:drug effects; D017448:Receptors, Dopamine D2; D012016:Reference Values; D013134:Spiperone / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*
D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D013134:Spiperone; D009075:MSH Release-Inhibiting Hormone