Abstract
Iron deficiency impairs nigrostriatal and mesolimbic dopamine systems by causing decreased densities of D1 and D2 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 813-819 |
| Number of pages | 7 |
| Journal | Pharmacology Biochemistry and Behavior |
| Volume | 73 |
| Issue number | 4 |
| DOIs | |
| State | Published - Nov 1 2002 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Toxicology
- Pharmacology
- Clinical Biochemistry
- Biological Psychiatry
- Behavioral Neuroscience
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Iron deficiency in rats decreases acquisition of and suppresses responding for cocaine. / Jones, Byron C.; Wheeler, Daniel S.; Beard, John L.; Grigson-Kennedy, Patricia "Sue".
In: Pharmacology Biochemistry and Behavior, Vol. 73, No. 4, 01.11.2002, p. 813-819.Research output: Contribution to journal › Article
TY - JOUR
T1 - Iron deficiency in rats decreases acquisition of and suppresses responding for cocaine
AU - Jones, Byron C.
AU - Wheeler, Daniel S.
AU - Beard, John L.
AU - Grigson-Kennedy, Patricia "Sue"
PY - 2002/11/1
Y1 - 2002/11/1
N2 - Iron deficiency impairs nigrostriatal and mesolimbic dopamine systems by causing decreased densities of D1 and D2 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.
AB - Iron deficiency impairs nigrostriatal and mesolimbic dopamine systems by causing decreased densities of D1 and D2 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.
UR - http://www.scopus.com/inward/record.url?scp=0036830060&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036830060&partnerID=8YFLogxK
U2 - 10.1016/S0091-3057(02)00906-1
DO - 10.1016/S0091-3057(02)00906-1
M3 - Article
C2 - 12213526
AN - SCOPUS:0036830060
VL - 73
SP - 813
EP - 819
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
SN - 0091-3057
IS - 4
ER -