PMID- 14698755 OWN - NLM STAT- MEDLINE DCOM- 20040512 LR - 20190712 IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 123 IP - 2 DP - 2004 TI - Prenatal cocaine exposure alters potassium-evoked dopamine release dynamics in rat striatum. PG - 481-90 AB - 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. FAU - Salvatore, M F AU - Salvatore MF AD - 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 FAU - Hudspeth, O AU - Hudspeth O FAU - Arnold, L E AU - Arnold LE FAU - Wilson, P E AU - Wilson PE FAU - Stanford, J A AU - Stanford JA FAU - MacTutus, C F AU - MacTutus CF FAU - Booze, R M AU - Booze RM FAU - Gerhardt, G A AU - Gerhardt GA LA - eng GR - AG06434/AG/NIA NIH HHS/United States GR - AG13494/AG/NIA NIH HHS/United States GR - DA11337/DA/NIDA NIH HHS/United States GR - DA14944/DA/NIDA NIH HHS/United States GR - MH01245/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Dopamine Plasma Membrane Transport Proteins) RN - 0 (Dopamine Uptake Inhibitors) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Transport Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Slc6a3 protein, rat) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - I5Y540LHVR (Cocaine) RN - RWP5GA015D (Potassium) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Brain Chemistry/drug effects MH - Cocaine/*toxicity MH - Corpus Striatum/*drug effects/growth & development/metabolism MH - Dopamine/*metabolism MH - Dopamine Plasma Membrane Transport Proteins MH - Dopamine Uptake Inhibitors/*toxicity MH - Female MH - Immunoblotting MH - Immunohistochemistry MH - Male MH - *Membrane Glycoproteins MH - Membrane Transport Proteins/analysis/metabolism MH - Microelectrodes MH - *Nerve Tissue Proteins MH - Neurons/drug effects/metabolism MH - Potassium/pharmacology MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - Rats MH - Tyrosine 3-Monooxygenase/analysis/metabolism EDAT- 2003/12/31 05:00 MHDA- 2004/05/13 05:00 CRDT- 2003/12/31 05:00 PHST- 2003/12/31 05:00 [pubmed] PHST- 2004/05/13 05:00 [medline] PHST- 2003/12/31 05:00 [entrez] AID - S0306452203007772 [pii] AID - 10.1016/j.neuroscience.2003.10.002 [doi] PST - ppublish SO - Neuroscience. 2004;123(2):481-90. doi: 10.1016/j.neuroscience.2003.10.002.