Better explicating the strengths and shortcomings of these models will help refine projections and improve transparency in the years ahead.
Image credit: Witsawat.S.
Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved April 16, 1998 (received for review December 12, 1997)
Abstract
Cocaine and methylphenidate block uptake by neuronal plasma membrane transporters for dopamine, serotonin, and norepinephrine. Cocaine also blocks voltage-gated sodium channels, a property not shared by methylphenidate. Several lines of evidence have suggested that cocaine blockade of the dopamine transporter (DAT), perhaps with additional contributions from serotonin transporter (5-HTT) recognition, was key to its rewarding actions. We now report that knockout mice without DAT and mice without 5-HTT establish cocaine-conditioned place preferences. Each strain displays cocaine-conditioned place preference in this major mouse model for assessing drug reward, while methylphenidate-conditioned place preference is also maintained in DAT knockout mice. These results have substantial implications for understanding cocaine actions and for strategies to produce anticocaine medications.
Footnotes
↵¶ To whom reprint requests should be sent at: Molecular Neurobiology, Box 5180, Baltimore, MD 21224. e-mail: guhl{at}irp.nida.nih.gov.
This paper was submitted directly (Track II) to the Proceedings Office.
Abbreviations: ES cells, embryonic stem cells; DAT, dopamine transporter; 5-HTT, serotonin transporter; TH, tyrosine hydroxylase.
- Received December 12, 1997.
- Copyright © 1998, The National Academy of Sciences
Cocaine reward models: Conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice
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