The effects of perinatal exposure to lead on the discriminative stimulus properties of cocaine and related drugs in rats.
BACKGROUND
Developmental lead exposure may alter responsiveness to cocaine well into adulthood, and ultimately influence drug-use patterns.


OBJECTIVE
The present study examined the effect of perinatal lead exposure on the discriminative stimulus properties of cocaine.


METHODS
Female rats were treated with 0, 8, or 16 mg lead daily for 30 days before breeding with untreated males. This exposure regimen continued through gestation and until postnatal day (PND) 21, i.e., weaning. At PND 60 male pups were trained to discriminate between saline and cocaine (5 mg/kg) injections. After acquisition, a series of generalization/substitution tests were performed using a cumulative dosing procedure.


RESULTS
Developmental lead exposure produced subsensitivity to SKF-82958 (D1-like dopamine receptor agonist), quinpirole (D2-like dopamine receptor agonist), and apomorphine (mixed D1-like/D2-like dopamine receptor agonist); but no differences were evident among lead-treatment groups on generalization/substitution tests with cocaine, d-amphetamine, or GBR-12909. Furthermore, when the kappa-opioid receptor agonist U69,593 was administered prior to cocaine (5 mg/kg), generalization to the cocaine stimulus decreased in control rats, but generalization in lead-exposed rats was not altered. Group differences were not evident in tolerance or recovery of tolerance to cocaine following repeated cocaine administration (60 mg/kg per day for 14 days). Furthermore, no differences were found across groups in concentrations of lead in brain, although pups exposed to 16 mg lead had slightly elevated blood lead concentrations (<7 microg/dl).


CONCLUSIONS
These results further a growing research literature that suggests developmental lead exposure can produce long-lasting changes in drug responsiveness, even after exposure to the toxicant has been discontinued.
Miller
D K
DK
College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
Nation
J R
JR
Bratton
G R
GR
D000818:Animals; D000831:Animals, Newborn; D003042:Cocaine / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects* / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009942:Organometallic Compounds / Q000378:metabolism / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists; D015203:Reproducibility of Results
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D009942:Organometallic Compounds; D011957:Receptors, Opioid; D003042:Cocaine; C008261:lead acetate