The effects of perinatal exposure to lead on the discriminative stimulus properties of cocaine and related drugs in rats

Rationale: Developmental lead exposure may alter responsiveness to cocaine well into adulthood, and ultimately influence drug-use patterns. Objectives : The present study examined the effect of perinatal lead exposure on the d iscriminative stimulus properties of cocaine. Methods: Female rats were tre ated with 0, 8, or 16 mg lead daily for 30 days before breeding with untrea ted males. This exposure regimen continued through gestation and until post natal day (PND) 21, i.e., weaning. At PND 60 male pups were trained to disc riminate between saline and cocaine (5 mg/kg) injections. After acquisition , a series of generalization/substitution tests were performed using a cumu lative dosing procedure. Results: Developmental lead exposure produced subs ensitivity to SKF-82958 (D-1-like dopamine receptor agonist), quinpirole (D -2-like dopamine receptor agonist), and apomorphine (mixed D-1-like/D-2-lik e dopamine receptor agonist); but no differences were evident among lead-tr eatment groups on generalization/substitution tests with cocaine, d-ampheta mine, or GBR-12909. Furthermore, when the K-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 rat s was not altered. Group differences were not evident in tolerance or recov ery of tolerance to cocaine following repeated cocaine administration (60 m g/kg per day for 14 days). Furthermore, no differences were found across gr oups in concentrations of lead in brain, although pups exposed to 16 mg lea d had slightly elevated blood lead concentrations (<7 <mu>g/dl). Conclusion s: These results further a growing research literature that suggests develo pmental lead exposure can produce long-lasting changes in drug responsivene ss, even after exposure to the toxicant has been discontinued.