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Research ArticleNEUROPHARMACOLOGY

Methylphenidate Restores Ventral Tegmental Area Dopamine Neuron Activity in Prenatal Ethanol-Exposed Rats by Augmenting Dopamine Neurotransmission

Kar-Chan Choong and Roh-Yu Shen
Journal of Pharmacology and Experimental Therapeutics May 2004, 309 (2) 444-451; DOI: https://doi.org/10.1124/jpet.103.060657
Kar-Chan Choong
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Roh-Yu Shen
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Abstract

Altered neurotransmission in the mesolimbic dopamine (DA) system has been suggested to be the underlying cause of attention problems commonly observed in children with fetal alcohol spectrum disorder (FASD). Methylphenidate is effective in treating attention problems in children with FASD. However, the underlying mechanism is currently unknown. We have shown previously that reduced ventral tegmental area (VTA) DA neuron activity in prenatal ethanol-exposed animals can be normalized by DA agonist treatment. In the present study, we investigated the possibility that similar mechanism mediates the effect of methylphenidate using the in vivo extracellular single-unit recording technique in anesthetized animals. We observed that reduced VTA DA neuron activity in prenatal ethanol-exposed animals was normalized by methylphenidate. The effect of methylphenidate was mediated by increased extracellular levels of DA instead of norepinephrine because this effect was not altered by the coadministration of prazosin, an α1 receptor antagonist, and was mimicked by the application of DA transporter blockers, nomifensine and 1-2(-[bis(4-flurophenyl)methoxy]ethyl)-4-(3-phenyl)piperazine dihydrochloride (GBR 12909). These observations support our hypothesis that depolarization inactivation is the cause of prenatal ethanol exposure-induced reduction in VTA DA neuron activity. We speculate that methylphenidate normalized the activity of VTA DA neurons by increasing extracellular DA levels in the VTA and the activation of somatodendritic DA autoreceptors. As a result, the depolarization inactivation was removed by hyperpolarization. The normalized VTA DA neuron activity in prenatal ethanol-exposed animals may contribute to a restoration of DA neurotransmission and the therapeutic effect of methylphenidate in attention problems in children with FASD.

Footnotes

  • ABBREVIATIONS: DA, dopamine; FASD, fetal alcohol spectrum disorder; VTA, ventral tegmental area; ANOVA, analysis of variance; LSD, least significant difference; ANCOVA, analysis of covariance; ADHD, attention deficit/hyperactivity disorder; GBR 12909, 1-2(-[bis(4-flurophenyl)methoxy]ethyl)-4-(3-phenyl)piperazine dihydrochloride.

  • This research was supported by AA09829 from the National Institute on Alcohol Abuse and Alcoholism.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • DOI: 10.1124/jpet.103.060657.

    • Received September 30, 2003.
    • Accepted December 31, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 309 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 309, Issue 2
1 May 2004
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Research ArticleNEUROPHARMACOLOGY

Methylphenidate Restores Ventral Tegmental Area Dopamine Neuron Activity in Prenatal Ethanol-Exposed Rats by Augmenting Dopamine Neurotransmission

Kar-Chan Choong and Roh-Yu Shen
Journal of Pharmacology and Experimental Therapeutics May 1, 2004, 309 (2) 444-451; DOI: https://doi.org/10.1124/jpet.103.060657

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Research ArticleNEUROPHARMACOLOGY

Methylphenidate Restores Ventral Tegmental Area Dopamine Neuron Activity in Prenatal Ethanol-Exposed Rats by Augmenting Dopamine Neurotransmission

Kar-Chan Choong and Roh-Yu Shen
Journal of Pharmacology and Experimental Therapeutics May 1, 2004, 309 (2) 444-451; DOI: https://doi.org/10.1124/jpet.103.060657
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