Prenatal cocaine exposure alters potassium-evoked dopamine release dynamics in rat striatum

Michael Francis Salvatore, O. Hudspeth, L. E. Arnold, P. E. Wilson, J. A. Stanford, C. F. MacTutus, R. M. Booze, G. A. Gerhardt

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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 (1×/day), GD 15-21 (2×/day), or GD 8-21 (1×/day-GD 8-14, 2×/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 (T80) 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.

Original languageEnglish
Pages (from-to)481-490
Number of pages10
JournalNeuroscience
Volume123
Issue number2
DOIs
StatePublished - 1 Jan 2004

Fingerprint

Cocaine
Dopamine
Potassium
Dopamine Plasma Membrane Transport Proteins
Dopaminergic Neurons
Long Evans Rats
Neurogenesis
Tyrosine 3-Monooxygenase
Parturition
Proteins

Keywords

  • Dopamine transporter
  • High-speed chronoamperometry
  • Nucleus accumbens
  • Prenatal cocaine
  • Striatum
  • Tyrosine hydroxylase

Cite this

Salvatore, M. F., Hudspeth, O., Arnold, L. E., Wilson, P. E., Stanford, J. A., MacTutus, C. F., ... Gerhardt, G. A. (2004). Prenatal cocaine exposure alters potassium-evoked dopamine release dynamics in rat striatum. Neuroscience, 123(2), 481-490. https://doi.org/10.1016/j.neuroscience.2003.10.002
Salvatore, Michael Francis ; Hudspeth, O. ; Arnold, L. E. ; Wilson, P. E. ; Stanford, J. A. ; MacTutus, C. F. ; Booze, R. M. ; Gerhardt, G. A. / Prenatal cocaine exposure alters potassium-evoked dopamine release dynamics in rat striatum. In: Neuroscience. 2004 ; Vol. 123, No. 2. pp. 481-490.
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Salvatore, MF, Hudspeth, O, Arnold, LE, Wilson, PE, Stanford, JA, MacTutus, CF, Booze, RM & Gerhardt, GA 2004, 'Prenatal cocaine exposure alters potassium-evoked dopamine release dynamics in rat striatum', Neuroscience, vol. 123, no. 2, pp. 481-490. https://doi.org/10.1016/j.neuroscience.2003.10.002

Prenatal cocaine exposure alters potassium-evoked dopamine release dynamics in rat striatum. / Salvatore, Michael Francis; Hudspeth, O.; Arnold, L. E.; Wilson, P. E.; Stanford, J. A.; MacTutus, C. F.; Booze, R. M.; Gerhardt, G. A.

In: Neuroscience, Vol. 123, No. 2, 01.01.2004, p. 481-490.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Salvatore, Michael Francis

AU - Hudspeth, O.

AU - Arnold, L. E.

AU - Wilson, P. E.

AU - Stanford, J. A.

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