 |
| Research article summary (published 26 Jan 2009): |
|
Free Full Text! See links below |
Dramatically decreased cocaine self-administration in dopamine but not serotonin transporter knock-out mice.
Full Abstract
There has been much interest in the relative importance of dopamine and serotonin transporters in the abuse-related-effects of cocaine. We tested the hypotheses that mice lacking the dopamine transporter (DAT(-/-)), the serotonin transporter (SERT(-/-)), or both (DAT(-/-)SERT(-/-)) exhibit decreased reinforcing effects of cocaine. We also assessed whether observed effects on self-administration are specific to cocaine or if operant behavior maintained by food or a direct dopamine agonist are similarly affected. We used a broad range of experimental conditions that included acquisition without previous training, behavior established with food training and subsequent testing with food, cocaine or a direct dopamine agonist as reinforcers, fixed ratio and progressive ratio schedules of reinforcement, and a reversal procedure. Wild-type mice readily acquired cocaine self-administration and showed dose-response curves characteristic of the schedule of reinforcement that was used. While some DAT(-/-) mice appeared to acquire cocaine self-administration transiently, almost all DAT(-/-) mice failed to self-administer cocaine reliably. Food-maintained behaviors were not decreased by the DAT mutation, and IV self-administration of a direct dopamine agonist was robust in the DAT(-/-) mice. In contrast to those mice, cocaine's reinforcing effects were not diminished in SERT(-/-) mice under any of the conditions tested, except for impaired initial acquisition of both food- and cocaine-maintained behavior. These findings support the notion that the DAT, but not the SERT, is critical in mediating the reinforcing effects of cocaine.
Author information
Author/s: Thomsen, Morgane (M); Hall, F Scott (FS); Uhl, George R (GR); Caine, S Barak (SB);
Affiliation: Alcohol and Drug Abuse Research Center, McLean Hospital-Harvard Medical School, Belmont, Massachusetts 02478, USA. mthomsen(-atsign-)mclean.harvard.edu
Grants: DA07252 (Agency:NIDA NIH HHS) ; DA12142 (Agency:NIDA NIH HHS) ; DA14528 (Agency:NIDA NIH HHS) ; DA14644 (Agency:NIDA NIH HHS) ; DA17323 (Agency:NIDA NIH HHS) ; R29 DA012142-01 (Agency:NIDA NIH HHS)
Journal and publication information
Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural
Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)
Reference: 2009-Jan; vol 29 (issue 4) : pp 1087-92
Dates: Created 2009/01/29; Completed 2009/04/08; Revised 2009/09/21;
PMID: 19176817, status: MEDLINE (last retrieval date: 9/22/2009, IMS Date: 22 Sep 2009 00:00:00)
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
External Links for this article
(including full text providers, if available):
Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.
This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.
MeSH headings (categories)
This article was linked to the MESH Headings shown below.
Related articles
This article has not been indexed for related articles as yet, however you can still use the live related article search links below.
See a large map of 100+ related articles.