Nutritional iron and dopamine binding sites in the rat brain.
Iron-deficiency (ID) anemia in man is associated with neurological disorders and abnormal behavior. Rats made nutritionally iron-deficient have markedly diminished behavioral responses to centrally-acting drugs (amphetamine and apomorphine) which affect monoaminergic systems. ID has no effect on either the levels of monoamines or on the activities of monoamine-metabolizing enzymes in the brain. We have investigated the possibility that ID may affect postsynaptic events at the level of receptor by measuring the specific binding sites of several neurotransmitters in different brain areas. The results clearly show that ID causes a significant (40-60%) reduction of the DA D2 binding sites in the caudate. DA-sensitive adenylate cyclase, alpha- and beta-adrenergic, muscarinic cholinergic and the benzodiazepine binding sites were not affected by ID. The effects of ID on DA D2 binding sites and the behavioral responses to apomorphine can be reversed when iron-deficient rats are placed for 8 days on an iron-deficient diet supplemented with iron. Chronic hemolytic anemia produced by repeated phenylhydrazine injections caused no change in serum iron and had no effect on either apomorphine-induced hyperactivity or 3H-spiroperidol binding in the caudate. Since the highest concentration of iron is found in DA-rich brain areas, it is possible that iron may be crucial to either the synthesis or coupling of the DA D2 binding site. The possibility that the DA supersensitivity induced by neuroleptics may be related to iron metabolism in the brain has been investigated.
D000743:Anemia, Hemolytic / Q000378:metabolism*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D005296:Ferrous Compounds / Q000494:pharmacology*; D006454:Hemoglobins / Q000378:metabolism; D007501:Iron / Q000097:blood / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*
D005296:Ferrous Compounds; D006454:Hemoglobins; D000644:Quaternary Ammonium Compounds; D011954:Receptors, Dopamine; C038178:ammonium ferrous sulfate; D007501:Iron; D001058:Apomorphine