In spite of 20 years of investigations of the effects of prenatal cocaine exposure in rodents, no one has modeled the binge pattern associated with smoking crack/cocaine in a pregnant rat. Cocaine use has gone down nationwide, but there remains a substantial number of individuals who have been exposed to crack/cocaine during prenatal life and the question remains, are the neurobehavioral alterations greater or perhaps less than those who have been exposed by other routes of administration? Crack smokers smoke repeatedly in a single binge. The rapidly increasing and decreasing blood/brain levels of cocaine as produced by smoking crack result in the greatest """"""""reinforcement"""""""" to the smoker and presumably result in parallel fetal exposure. The effects of these rapidly increasing and decreasing cocaine levels during gestation are for the most part unknown.
Aim 1 of this application will establish a binge model of crack/cocaine abuse during pregnancy in the rat using an indwelling jugular port and repeated rapid intravenous dosing.
Aim 2 will determine peak and clearance of cocaine and metabolites in blood and brain to facilitate a comparison with maternal and fetal exposures of human crack smokers. Also, this aim will determine whether a single cocaine binge will result in detectable fetal cocaine and metabolite levels. Together, these studies will develop a translational model of crack smoking during pregnancy to set the stage for future studies especially on the effects of binge cocaine exposure on the development of reward systems known to be affected by the binge pattern of cocaine administration.
This application will develop a rat model of crack/cocaine bingeing during pregnancy in humans. We will utilize indwelling jugular ports to administer cocaine binges IV both before and during pregnancy in the rat since IV closely approximates the pharmacokinetics of smoking crack. Additionally, we will assess the blood and brain levels of cocaine and metabolites resulting from chronic bingeing to enable comparisons with human exposures.
|Dow-Edwards, Diana (2011) Translational issues for prenatal cocaine studies and the role of environment. Neurotoxicol Teratol 33:9-16|