|
Description:
|
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 . |