The effects of bicuculline on cocaine self-administration in male rats developmentally exposed to lead

Rationale: Lead-exposure during developmental periods may alter reinforcing patterns of drugs of abuse in adulthood. Anxiety related mechanisms may also influence drug intake. Interactions between the two altering factors may exist. Objectives: The present study examined the effects of perinatal lead-exposure on cocaine self-administration after a GABAA antagonist pre-treatment. Methods: Female rats were exposed to a regimen of 16 mg lead daily for 30 days prior to breeding with un-exposed males. This continued throughout gestation and lactation until postnatal day (PND) 21. On PND 63, animals were implanted with indwelling jugular catheters. After a 7 day recovery period, animals were trained to self-administer 0.50 mg/kg cocaine intravenously [IV]. After stable responding had been established, testing procedures began using combinations of 0.03 and 0.06 mg/kg cocaine [IV] and 0.00, 0.50, 1.00 and 2.00 mg/kg bicuculline (a GABAA antagonist) intraperitoneal [IP]. Results: Bicuculline pre-treatment caused directionally opposite effects in both treatment groups (Group 0-Lead and Group 16-Lead) at the 0.06 mg/kg cocaine dose. Group 0-Lead animals showed an increase in self-administration, while Group 16-Lead animals showed a decrease in responding on the active (cocaine) lever. Results at the 0.03 mg/kg cocaine dose showed no discernable pattern. Group 0-Lead animals decreased in active lever responding at the 2.00 mg/kg bicuculline dose. Group 16-Lead animals showed no differences in responding at any dose of bicuculline. Conclusions: These data further suggest the influential role of GABA in mediating cocaine reward and the ability of developmental lead-exposure to alter mechanisms mediating drug responsiveness even after exposure has terminated.