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Ernest Gallo Research Center, Department of Neurology, University of California, San Francisco, Emeryville, California, USA
1Correspondence: 5858 Horton St., Suite 200, Emeryville, CA 94608, USA. E-mail: dorit.ron{at}ucsf.edu
We apologize greatly for the misstatement in the discussion noted by Drs. Walker and Koob and are very appreciative that they have caught this mistake before the final publication of the article.
We hope that these errors may be changed to reflect the intended meaning, as listed below. The sentences in question are as follows: "This loss of dynorphin feedback could result in oversensitivity of the KOR system, as suggested by Walker and Koob (74), who demonstrated that the KOR antagonist nor-BNI increased ethanol intake in ethanol-dependent rats but not in ethanol-experienced, nondependent rats. The inability of nor-BNI to increase ethanol intake in nondependent animals, as observed by us and others (75, 80), even after a period of alcohol deprivation (71), supports a role for dynorphin in between-bout rather than within-bout regulation of ethanol intake." In this paragraph, the first incidence of "increased" should have been "decreased," and the second occurrence should be "alter." Again, we apologize for the persistence of these typographical errors in the manuscript.
The corrected paragraph is as follows: "This loss of dynorphin feedback could result in oversensitivity of the KOR system, as suggested by Walker and Koob (74), who demonstrated that the KOR antagonist nor-BNI decreased ethanol intake in ethanol-dependent rats but not in ethanol-experienced, nondependent rats. The inability of nor-BNI to alter ethanol intake in nondependent animals, as observed by ourselves and others (75, 80), even after a period of alcohol deprivation (71), supports a role for dynorphin in between-bout rather than within-bout regulation of ethanol intake."
As briefly mentioned in this paragraph of the discussion, we believe that KOR regulation of ethanol intake in nondependent animals involves a between-session, rather than a within-session, alteration of ethanol drinking. However, BDNF regulation of dynorphin expression is an acute response to ethanol intake—one we believe homeostatically regulates ethanol intake, thus protecting against the development of dependence, and which is spatially restricted to the dorsal striatum. In dependent animals, we hypothesize that dorsal striatal BDNF will no longer regulate ethanol intake, likely because BDNF expression becomes nonresponsive to ethanol after prolonged exposure, as we have previously shown to be the case in vitro (1)
. We are currently testing this hypothesis in vivo as well—namely that BDNF reduction of ethanol intake breaks down after extensive ethanol experience, coincident with the development of dependence.
According to this hypothesis, dynorphin expression will be regulated by mechanisms independent of BDNF in dependent animals and will no longer provide feedback after acute ethanol drinking bouts. In addition, since this BDNF/dynorphin pathway is restricted to the dorsal striatum, alterations in the activity of the dynorphin/kappa opioid receptor system in various other brain regions, in particular the regions of the mesolimbic reward pathway, may be critical to the reduction in ethanol intake observed after nor-BNI treatment of dependent animals (2)
. As Drs. Walker and Koob suggest, this likely coincides with a dysphoric state produced by ethanol withdrawal which is not observed in nondependent animals, thus yielding the ineffectiveness of nor-BNI to alter ethanol intake in the absence of ethanol dependence. In our case, we observed a slight decrease in ethanol intake in nondependent animals, but importantly, we found that nor-BNI treatment blocked the decrease in ethanol intake produced by Tat-RACK1 treatment, which increases BDNF expression (1)
. As nor-BNI treatment alone did not differ from treatment with Tat-RACK1 + nor-BNI, these data indicate that dynorphin activation of the KOR is required for BDNF to modulate ethanol intake.
Again, we would like to apologize for this mistake and thank Drs. Walker and Koob for catching this error prior to the print publication of this article.
ACKNOWLEDGMENTS
Managing Editor’s Note: The final version of this article contains the corrections described by D. Ron.
FOOTNOTES
The opinions expressed in editorials, essays, letters to the editor, and other articles comprising the Up Front section are those of the authors and do not necessarily reflect the opinions of FASEB or its constituent societies. The FASEB Journal welcomes all points of view and many voices. We look forward to hearing these in the form of op-ed pieces and/or letters from its readers addressed to journals{at}faseb.org
REFERENCES
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