title: Prenatal cocaine exposure alters potassium-evoked dopamine release dynamics in rat striatum.
abstract: The emerging profile for the effects of prenatal cocaine exposure presents two prominent features in the exposed offspring: cognitive/attention deficits and an age-associated trend toward motor/tone abnormalities up to 2 years of age. One candidate mechanism underlying these clinical features is long-lasting alterations to dopamine (DA) neuron function. However, the impact of prenatal cocaine exposure on DA release in dopaminergic terminal fields in vivo in mature offspring is poorly understood. Long-Evans female rats were implanted with an i.v. access port, bred, and given saline or cocaine-HCl (3 mg/kg/ml) for gestational days (GD) 8-14 (1x/day), GD 15-21 (2x/day), or GD 8-21 (1x/day-GD 8-14, 2x/day-GD 15-21). Using in vivo high-speed chronoamperometric recordings, potassium-stimulated DA release was measured in striatum of anesthetized male offspring 90-150 days after birth. There was a trend toward increased potassium-evoked DA signal amplitudes in offspring exposed to cocaine at any time period examined. In offspring exposed to cocaine during GD 8-21 and GD 15-21, but not at GD 8-14, there were significant decreases in the clearance capacity of the potassium-evoked DA signal compared with control offspring. The time required to clear 80% of the evoked DA signal (T(80)) in striatum for DA was significantly prolonged (approximately 150% of control) and this effect was further increased in the mean-evoked DA concentration range for these two groups. We also measured total dopamine transporter (DAT) and tyrosine hydroxylase protein levels in these offspring by blot immunolabeling and found a small, but significant, decrease in DAT protein in striatum from offspring exposed at GD 8-21 and GD 15-21. Collectively, these data demonstrate that prenatal cocaine exposure during dopamine neuron neurogenesis has long-lasting effects on DA neuron function lasting into early adulthood which may be related in part to steady state DAT protein levels. These molecular events may be associated with established cognitive deficits and perhaps the trends seen in altered motor behavior.
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky Medical Center, Center for Sensor Technology, Davis Mills Building, 800 Rose Street, Lexington, KY 40536, USA. msalv2@uky.edu
authors.forename: M F
authors.initials: MF
authors.lastname: Salvatore
authors.forename: O
authors.initials: O
authors.lastname: Hudspeth
authors.forename: L E
authors.initials: LE
authors.lastname: Arnold
authors.forename: P E
authors.initials: PE
authors.lastname: Wilson
authors.forename: J A
authors.initials: JA
authors.lastname: Stanford
authors.forename: C F
authors.initials: CF
authors.lastname: MacTutus
authors.forename: R M
authors.initials: RM
authors.lastname: Booze
authors.forename: G A
authors.initials: GA
authors.lastname: Gerhardt
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003042:Cocaine / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D005260:Female; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism; D008839:Microelectrodes; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493216:Slc6a3 protein, rat; D014446:Tyrosine 3-Monooxygenase; D003042:Cocaine; D011188:Potassium; D004298:Dopamine