Iron deficiency in rats decreases acquisition of and suppresses responding for cocaine.

Iron deficiency impairs nigrostriatal and mesolimbic dopamine systems by causing decreased densities of D(1) and D(2) receptors and the dopamine transporter in the terminal fields, caudate-putamen and nucleus accumbens. Iron deficiency also causes deficits in dopamine-related pharmacological indices, e.g., deficits in locomotor stimulation by cocaine and locomotor inhibition by raclopride. Based on this knowledge, we hypothesized that iron deficiency would have a major impact on cocaine self-administration. Male Sprague-Dawley rats were fed an iron-deficient diet starting at weaning (Day 21) and continuing throughout the experiment. At 57-58 days of age, all animals had catheters implanted surgically into the jugular vein. Approximately 2 weeks later, all animals were trained to lick an empty spout for intravenous cocaine, delivered by infusion pump at 0.33 mg/kg. During the course of training, all animals acquired intravenous cocaine self-administration, however, the course of acquisition was significantly slower for the iron-deficient animals. When tested for responding on a progressive ratio (PR) schedule, the control animals maintained a constant number of infusions, whereas the responding of the iron-deficient animals fell off sharply. When the dose of cocaine was decreased, control, but not iron-deficient adjusted the amount administered by increasing the number of infusions. Finally, the failure to respond by the iron-deficient animals was not simply due to a failure to lick (i.e., a motor impairment), because both the iron-deficient and the control animals emitted approximately 1000 licks/20 min session when given free access to a palatable 0.1 M sucrose solution. Taken together, the data show that severe iron deficiency early in life can diminish the capacity of cocaine, but not sucrose to reinforce behavior. The question raised by this research thus, is whether iron deficiency alters hedonic-like responses only to dopamine-related behaviors and the degree to which willingness to "work" contributes to the effect.