Brain iron and dopamine receptor function.

Abstract

It has been demonstrated that nutritional iron-deficiency induced in rats results in the reduction of DA D2 receptor binding sites, leading to down-regulation of dopaminergic activity similar to that observed in neuroleptic-treated animals. The following observations are common to both conditions: (a) Decreased behavioural response to pre- and post-synaptically DA and serotonin acting drugs, amphetamine, apomorphine and 5-methoxy-N,N-dimethyltryptamine. (b) Inhibition of amphetamine or apomorphine induced hypothermia in rats kept at an ambient temperature of 4 degrees C. (c) Increased sleeping time to phenobarbitone which cannot be attributed to the rate of drug metabolism (5,38). (d) Upregulation of prolactin binding sites in the liver as a result of increased serum prolactin. Additionally, nutritional iron-deficiency lowers brain iron and interferes with protein synthesis in this organ, which could explain the reduction of DA D2 receptor number and function. Given the fact that the highest brain concentrations of iron are found in dopaminergic structures (see 42 for review), and the essential role of intact dopaminergic systems to attentional and learning processes (15b,30), the resultant behavioural changes due to the reduction of dopaminergic activity in iron-deficient animals may go some way to explain the adverse effects on cognition, behavioural patterns, learning and attention, event-related potentials (ERPs) and EEG changes reported in iron-deficient children (19-28,30).