Choosing under the influence: A drug-specific mechanism by which the setting controls drug choices in rats
Neuropsychopharmacol. 2015-07-01; 41(2): 646-657
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1. Neuropsychopharmacology. 2016 Jan;41(2):646-57. doi: 10.1038/npp.2015.195. Epub
2015 Jul 1.
Choosing Under the Influence: A Drug-Specific Mechanism by Which the Setting
Controls Drug Choices in Rats.
Vandaele Y(1)(2), Cantin L(3), Serre F(4), Vouillac-Mendoza C(1)(2), Ahmed
(1)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR CNRS
5293, Bordeaux, France.
(2)Institut des Maladies Neurodégénératives, UMR CNRS 5293, Bordeaux, France.
(3)Institut Bergonié, Bordeaux, France.
(4)SANPSY, CNRS USR 3413, Université de Bordeaux, Bordeaux, France.
Ample evidence shows that the setting can control drug choices in both humans and
animals. Here we reveal in rats that a major mechanism of this control involves a
regulation of the drug influence on other competing options at the time of
choice. Briefly, rats were offered a choice between a drug dose (cocaine or
heroin) and a brief access to water sweetened with saccharin in two different
settings. In one setting, choosing under the influence was not possible and rats
largely preferred saccharin over either cocaine or heroin. In contrast, when the
same rats were shifted to a setting where choosing under the influence was
possible, they chose the drug either nonexclusively or exclusively depending on
whether the drug enhanced or suppressed sweet reward, respectively. Thus, when
rats were under the orexigenic influence of heroin at the time of choice, they
more frequently chose saccharin in alternation with heroin. In contrast, when
rats were under the anorexic influence of cocaine, they stopped choosing
saccharin and continued taking cocaine exclusively. These setting- and
drug-specific changes in preference were rapid and reversible, and could be
induced by passively administering cocaine or heroin before choice. Finally, rats
behaved as if they were oblivious to the drug influence on their choices. This
behavior could explain why rats are vulnerable to harm themselves, sometimes to
the point of death, in settings where choices are made under the drug influence,
notably if this influence excludes other important options or, conversely,
enhances harmful ones.
PMID: 26129679 [Indexed for MEDLINE]