title: Preweaning iron deficiency increases non-contingent responding during cocaine self-administration in rats.
abstract: Iron deficiency (ID) is the most prevalent single-nutrient deficiency worldwide. There is evidence that ID early in development (preweaning in rat) causes irreversible neurologic, behavioral, and motor development deficits. Many of these effects have been attributed to damage to dopamine systems, including ID-induced changes in transporter and receptor numbers in the striatum and nucleus accumbens. These mesolimbic dopaminergic neurons are, in part, responsible for mediating reward and thus play a key role in addiction. However, there has been relatively little investigation into the behavioral effects of ID on drug addiction. In 2002, we found that rats made ID from weaning (postnatal day 21) and throughout the experiment acquired cocaine self-administration significantly more slowly than controls and failed to increase responding when the dose of the drug was decreased. In the present study, we assessed addiction for self-administered cocaine in rats with a history of preweaning ID only during postnatal days 4 through 21, and iron replete thereafter. The results showed that while ID did not affect the number of cocaine infusions or the overall addiction-like behavior score, ID rats scored higher on a measure of continued responding for drug than did iron replete controls. This increase in responding, however, was less goal-directed as ID rats also responded more quickly to the non-rewarded manipulandum than did control rats. Thus, while ID early in infancy did not significantly increase addiction-like behaviors for cocaine in this small study, the pattern of data suggests a possible underlying learning or performance impairment. Future studies will be needed to elucidate the exact neuro-behavioral deficits that lead to the increase in indiscriminate responding for drug in rats with a history of perinatal ID.
authors.affiliation: Neural and Behavioral Sciences, Penn State Hershey College of Medicine, The Pennsylvania State University, United States.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Jenney
authors.affiliation: Neural and Behavioral Sciences, Penn State Hershey College of Medicine, The Pennsylvania State University, United States.
authors.forename: Danielle N
authors.initials: DN
authors.lastname: Alexander
authors.affiliation: Department of Biobehavioral Health, The Pennsylvania State University, United States.
authors.forename: Byron C
authors.initials: BC
authors.lastname: Jones
authors.affiliation: Department of Biobehavioral Health, The Pennsylvania State University, United States.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Unger
authors.affiliation: Neural and Behavioral Sciences, Penn State Hershey College of Medicine, The Pennsylvania State University, United States. Electronic address: psg6@psu.edu.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Grigson
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced / Q000503:physiopathology*; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D000090463:Iron Deficiencies; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012055:Reinforcement Schedule; D012646:Self Administration
chemical_list: D018765:Dopamine Uptake Inhibitors; D006454:Hemoglobins; D003042:Cocaine
keywords: Addiction; Cocaine; Iron deficiency; Learning; Rat; Self-administration