Cocaine Is Low on the Value Ladder of Rats: Possible Evidence for Resilience to Addiction
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{"title"=>"Cocaine is low on the value ladder of rats: Possible evidence for resilience to addiction", "type"=>"journal", "authors"=>[{"first_name"=>"Lauriane", "last_name"=>"Cantin", "scopus_author_id"=>"23968052100"}, {"first_name"=>"Magalie", "last_name"=>"Lenoir", "scopus_author_id"=>"15848818400"}, {"first_name"=>"Eric", "last_name"=>"Augier", "scopus_author_id"=>"36607488100"}, {"first_name"=>"Nathalie", "last_name"=>"Vanhille", "scopus_author_id"=>"36609282000"}, {"first_name"=>"Sarah", "last_name"=>"Dubreucq", "scopus_author_id"=>"36167928900"}, {"first_name"=>"Fuschia", "last_name"=>"Serre", "scopus_author_id"=>"23968215800"}, {"first_name"=>"Caroline", "last_name"=>"Vouillac", "scopus_author_id"=>"8940872100"}, {"first_name"=>"Serge H.", "last_name"=>"Ahmed", "scopus_author_id"=>"7402716366"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"20676364", "doi"=>"10.1371/journal.pone.0011592", "sgr"=>"77955592122", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-77955592122", "issn"=>"19326203", "pui"=>"359358178"}, "id"=>"a48840ca-cdfb-3ba5-8d5c-9b5929011d06", "abstract"=>"BACKGROUND: Assessing the relative value of cocaine and how it changes with chronic drug use represents a long-standing goal in addiction research. Surprisingly, recent experiments in rats--by far the most frequently used animal model in this field--suggest that the value of cocaine is lower than previously thought. METHODOLOGY/PRINCIPAL FINDINGS: Here we report a series of choice experiments that better define the relative position of cocaine on the value ladder of rats (i.e., preference rank-ordering of different rewards). Rats were allowed to choose either taking cocaine or drinking water sweetened with saccharin--a nondrug alternative that is not biologically essential. By systematically varying the cost and concentration of sweet water, we found that cocaine is low on the value ladder of the large majority of rats, near the lowest concentrations of sweet water. In addition, a retrospective analysis of all experiments over the past 5 years revealed that no matter how heavy was past cocaine use most rats readily give up cocaine use in favor of the nondrug alternative. Only a minority, fewer than 15% at the heaviest level of past cocaine use, continued to take cocaine, even when hungry and offered a natural sugar that could relieve their need of calories. CONCLUSIONS/SIGNIFICANCE: This pattern of results (cocaine abstinence in most rats; cocaine preference in few rats) maps well onto the epidemiology of human cocaine addiction and suggests that only a minority of rats would be vulnerable to cocaine addiction while the large majority would be resilient despite extensive drug use. Resilience to drug addiction has long been suspected in humans but could not be firmly established, mostly because it is difficult to control retrospectively for differences in drug self-exposure and/or availability in human drug users. This conclusion has important implications for preclinical research on the neurobiology of cocaine addiction and for future medication development.", "link"=>"http://www.mendeley.com/research/cocaine-low-value-ladder-rats-possible-evidence-resilience-addiction", "reader_count"=>92, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>7, "Student > Doctoral Student"=>10, "Researcher"=>19, "Student > Ph. D. Student"=>15, "Student > Postgraduate"=>6, "Student > Master"=>8, "Other"=>4, "Student > Bachelor"=>18, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>7, "Student > Doctoral Student"=>10, "Researcher"=>19, "Student > Ph. D. Student"=>15, "Student > Postgraduate"=>6, "Student > Master"=>8, "Other"=>4, "Student > Bachelor"=>18, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>7, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>28, "Medicine and Dentistry"=>12, "Neuroscience"=>14, "Sports and Recreations"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>20, "Chemistry"=>1, "Social Sciences"=>3, "Economics, Econometrics and Finance"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>12}, "Neuroscience"=>{"Neuroscience"=>14}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>3}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Psychology"=>{"Psychology"=>20}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>28}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>7}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>2, "United Kingdom"=>1, "Kenya"=>1, "Australia"=>1, "Germany"=>1}, "group_count"=>4}

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Figshare

  • {"files"=>["http://files.figshare.com/838153/Figure_5.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "users"=>["Lauriane Cantin", "Magalie Lenoir", "Eric Augier", "Nathalie Vanhille", "Sarah Dubreucq", "Fuschia Serre", "Caroline Vouillac", "Serge H. Ahmed"], "links"=>[], "tags"=>["extinction", "responding"], "title"=>"<p>Concurrent extinction of responding for cocaine and saccharin.</p>", "figshare_url"=>"http://figshare.com/articles/_Concurrent_extinction_of_responding_for_cocaine_and_saccharin_/508518", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pone.0011592.g005"], "published_date"=>"2013-02-21 00:11:41", "article_id"=>508518, "categories"=>["Mental Health", "Neuroscience"], "description"=>"<p>During extinction testing, the lever previously associated with cocaine was presented concurrently with the lever previously associated with saccharin during 45 min. Pressing on either lever was recorded but had no programmed consequence (no response-contingent reward delivery or light cue presentation). (A) Bars represent the mean total number of responses (± s.e.m.) on the cocaine- and saccharin-associated levers over the 45-min extinction period. *, different from the other reward (<i>P</i><0.05, one-way ANOVA); (B) Curves represent within-session time course of extinction responding on the two levers (means ± s.e.m.). *, different from the other reward (<i>P</i><0.01, Fisher's LSD test following a two-way ANOVA).</p>"}
  • {"files"=>["http://files.figshare.com/838065/Figure_4.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "users"=>["Lauriane Cantin", "Magalie Lenoir", "Eric Augier", "Nathalie Vanhille", "Sarah Dubreucq", "Fuschia Serre", "Caroline Vouillac", "Serge H. Ahmed"], "links"=>[], "tags"=>["post-reward", "responding", "pr"], "title"=>"<p>Effects of post-reward delay on PR responding for cocaine.</p>", "figshare_url"=>"http://figshare.com/articles/_Effects_of_post_reward_delay_on_PR_responding_for_cocaine_/508425", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pone.0011592.g004"], "published_date"=>"2013-02-21 00:11:15", "article_id"=>508425, "categories"=>["Mental Health", "Neuroscience"], "description"=>"<p>Bars represent the means (± s.e.m.) over the last 3 stable testing sessions of: (A) total responses and (B) breakpoints as a function of reward type (cocaine versus saccharin) and of post-reward delay (0 versus 10 min). *, different from saccharin (<i>P</i><0.01, Fisher's LSD test following a two-way ANOVA); #, different from 0-min delay (<i>P</i><0.01, Fisher's LSD test following a two-way ANOVA).</p>"}
  • {"files"=>["http://files.figshare.com/837902/Figure_2.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "users"=>["Lauriane Cantin", "Magalie Lenoir", "Eric Augier", "Nathalie Vanhille", "Sarah Dubreucq", "Fuschia Serre", "Caroline Vouillac", "Serge H. Ahmed"], "links"=>[], "tags"=>["responding", "pr"], "title"=>"<p>Differential PR responding for cocaine and saccharin.</p>", "figshare_url"=>"http://figshare.com/articles/_Differential_PR_responding_for_cocaine_and_saccharin_/508267", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pone.0011592.g002"], "published_date"=>"2013-02-21 00:10:24", "article_id"=>508267, "categories"=>["Mental Health", "Neuroscience"], "description"=>"<p>Bars represent the means (± s.e.m.) over the last 3 stable testing sessions of: (A) total responses, (B) rewards earned and (C) breakpoints as a function of reward type [cocaine versus saccharin (sacc)]. *, different from sweet water [<i>P</i><0.01, one-way analysis of variance (ANOVA)].</p>"}
  • {"files"=>["http://files.figshare.com/838233/Figure_6.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "users"=>["Lauriane Cantin", "Magalie Lenoir", "Eric Augier", "Nathalie Vanhille", "Sarah Dubreucq", "Fuschia Serre", "Caroline Vouillac", "Serge H. Ahmed"], "links"=>[], "tags"=>["neuroscience/behavioral neuroscience", "neuroscience/animal cognition", "mental health/substance abuse", "mental health/psychopharmacology"], "title"=>"<p>Estimation of the relative value of cocaine.</p>", "figshare_url"=>"http://figshare.com/articles/_Estimation_of_the_relative_value_of_cocaine_/508597", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pone.0011592.g006"], "published_date"=>"2013-02-21 00:12:19", "article_id"=>508597, "categories"=>["Mental Health", "Neuroscience"], "description"=>"<p>Curves represent (A) choice between cocaine and water sweetened with saccharin and (B) percent of completed trials as a function of the relative cost of saccharin. The cost of saccharin was gradually increased either between sessions (open circles) or within sessions (closed circles). In the former case, each cost level was tested at least 5 times consecutively until stabilization of behavior. Data points represent the means (± s.e.m.) of the last 3 stable testing sessions. For other details, see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011592#s4\" target=\"_blank\">Materials and Methods</a>, and legend of <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011592#pone-0011592-g003\" target=\"_blank\">Figure 3</a>. *, different from the indifference level (<i>P</i><0.05, <i>t</i>-test).</p>"}
  • {"files"=>["http://files.figshare.com/837835/Figure_1.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "users"=>["Lauriane Cantin", "Magalie Lenoir", "Eric Augier", "Nathalie Vanhille", "Sarah Dubreucq", "Fuschia Serre", "Caroline Vouillac", "Serge H. Ahmed"], "links"=>[], "tags"=>["neuroscience/behavioral neuroscience", "neuroscience/animal cognition", "mental health/substance abuse", "mental health/psychopharmacology"], "title"=>"<p>Diagram of the design of the first experiment.</p>", "figshare_url"=>"http://figshare.com/articles/_Diagram_of_the_design_of_the_first_experiment_/508191", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pone.0011592.g001"], "published_date"=>"2013-02-21 00:09:56", "article_id"=>508191, "categories"=>["Mental Health", "Neuroscience"], "description"=>"<p >For additional information, see the text.</p>"}
  • {"files"=>["http://files.figshare.com/837991/Figure_3.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "users"=>["Lauriane Cantin", "Magalie Lenoir", "Eric Augier", "Nathalie Vanhille", "Sarah Dubreucq", "Fuschia Serre", "Caroline Vouillac", "Serge H. Ahmed"], "links"=>[], "tags"=>["neuroscience/behavioral neuroscience", "neuroscience/animal cognition", "mental health/substance abuse", "mental health/psychopharmacology"], "title"=>"<p>Comparison between reward assessment procedures.</p>", "figshare_url"=>"http://figshare.com/articles/_Comparison_between_reward_assessment_procedures_/508351", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pone.0011592.g003"], "published_date"=>"2013-02-21 00:10:50", "article_id"=>508351, "categories"=>["Mental Health", "Neuroscience"], "description"=>"<p>(A) Choice between water sweetened with saccharin and cocaine. The horizontal dashed line at 0 indicates the indifference level. Values above 0 indicate a preference for sweet water while values below 0 indicate a preference for intravenous cocaine. *, different from the first day (<i>P</i><0.05, Fisher's LSD test following a one-way ANOVA); #, different from the indifference level (<i>P</i><0.05, <i>t</i>-test). (B) Correlation between individual PR and preference scores. The x-axis corresponds to the PR score (difference in breakpoints between saccharin and cocaine; see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011592#s2\" target=\"_blank\">Results</a>) while the y-axis corresponds to the preference score as measured in the choice procedure (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011592#s4\" target=\"_blank\">Materials and Methods</a>). The vertical dashed line at 0 indicates that the breakpoint of cocaine was equal to that of sweet water. Values on the left or on the right of this vertical line indicate that the breakpoint of cocaine is higher or lower than the breakpoint of sweet water, respectively. Open circles represent individuals whose PR and preference scores are incongruent; closed circles represent individuals whose PR and preference scores are congruent. Note that rats with a PR score ≥-3 or ≤3 (i.e., only one step size in the PR3 schedule) were considered to work equally for both types of reward.</p>"}

PMC Usage Stats | Further Information

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