Large-scale characterization of cocaine addiction-like behaviors reveals that escalation of intake, aversion-resistant responding, and breaking-points are highly correlated measures of the same construct
- Department of Psychiatry, University of California, San Diego, United States
- Department of Neuroscience, The Scripps Research Institute, La Jolla, United States
- Institut de Neurosciences de la Timone, Aix-Marseille Université, France
- Institute for Genomic Medicine, University of California, San Diego, United States
- Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, United States
Figures
Figure 1 with 1 supplement
Individual differences in addiction behaviors in heterogeneous stock (HS) rats following intravenous cocaine self-administration.
(A) Timeline of the behavioral paradigms. (B) Number of cocaine infusions in the first hour of cocaine self-administration during short (2 hr, short access: ShA) and long (6 hr, long access: LgA) …
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Figure 1—source data 1
Raw data utilized for generating Figure 1.
‘Rat info Raw data’ tab contains the raw data table with all data analyzed, other tabs have the data split per panel in the figure as indicated. (B) Number of cocaine infusions per hour of cocaine self-administration during short (2 hr, short access: ShA) and long (6 hr, long access: LgA) access (N=567). (C) Average number of daily infusions for the last 3 days of LgA (N=567). (D) Number of cocaine infusions under progressive ratio (PR) tested after ShA (1) and LgA, before (2) and after (3) the Shock session (N=560). (E, F) Number of infusions despite footshock after LgA compared to a 1 h preshock session (N=466), with cohort number for correlation analysis. (G) Difference in irritability scores after LgA and at baseline (irritability) per type (aggressive, defensive, or total) and group (cocaine or naïve) (N=380 + 49 naïve). (H) Data for all sessions ShA1-10, LgA1-14, PR1-3, Shock with escalation, motivation, and compulsivity indices for principal component analysis (PCA).
- https://cdn.elifesciences.org/articles/90422/elife-90422-fig1-data1-v1.xlsx
Figure 1—figure supplement 1
Additional representations of the intake and lever presses are associated with Figure 1B.
(A) Total number of cocaine infusions during short (2 hr, short access: ShA) and long (6 hr, long access: LgA) access. (B) Percent of active or inactive lever presses of the total presses during …
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Figure 1—figure supplement 1—source data 1
Raw data utilized for generating Figure 1—figure supplement 1.
(A) Total number of cocaine infusions during short (2 hr, short access: ShA) and long (6 hr, long access: LgA) access. (B) Mean, standard deviation (sd), and standard error (se) of percent of active or inactive lever presses of the total presses during short access.
- https://cdn.elifesciences.org/articles/90422/elife-90422-fig1-figsupp1-data1-v1.xlsx
Figure 2
Sex differences in addiction-like behaviors.
(A) Cocaine infusions during short (2 hr, short access: ShA) and long (6 hr, long access: LgA) access of cocaine self-administration (N=275 F and 292 M, ###p<0.0001 vs males) (B) Average number of …
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Figure 2—source data 1
Raw data utilized for generating Figure 2.
Groups split by sex. ‘Rat info Raw data’ tab contains the raw data table with all data analyzed, other tabs have the data split per panel in the figure as indicated. (A) Number of cocaine infusions per hour of cocaine self-administration during short (2 hr, short access: ShA) and long (6 hr, long access: LgA) access, per sex (N=275 F and 292 M). (B) Average number of daily infusions for the last 3 days of LgA. (C) Number of cocaine infusions under progressive ratio (PR) tested after ShA or LgA (period). (D) Number of infusions despite footshock after LgA. (E) Difference in irritability scores after LgA and at baseline (irritability) per type (aggressive, defensive, or total) and group (cocaine or naïve) (N=380 + 49 naïve).
- https://cdn.elifesciences.org/articles/90422/elife-90422-fig2-data1-v1.xlsx
Figure 3 with 1 supplement
Addiction-like behaviors in resilient and vulnerable heterogeneous stock (HS) rats.
(A) Number of cocaine infusions during short (2 hr, short access: ShA) and long (6 hr, long access: LgA) access of cocaine self-administration in resilient and vulnerable animals (N=122 resilient …
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Figure 3—source data 1
Raw data utilized for generating Figure 3.
Groups are split by resilient and vulnerable animals. ‘Rat info Raw data’ tab contains the raw data table with all data analyzed, other tabs have the data split per panel in the figure as indicated. (A) Number of cocaine infusions per hour of cocaine self-administration during short (2 hr, short access: ShA) and long (6 hr, long access: LgA) access, split by resilient and vulnerable animals (N=122 resilient and 445 vulnerable). (B) Average number of daily infusions for the last 3 days of LgA, by vulnerability. (C) Number of cocaine infusions under progressive ratio (PR) tested after ShA or LgA (period). (D) Number of infusions despite footshock after LgA. (E) Difference in irritability scores after LgA and at baseline (irritability) per type (aggressive, defensive, or total) and group (cocaine or naïve).
- https://cdn.elifesciences.org/articles/90422/elife-90422-fig3-data1-v1.xlsx
Figure 3—figure supplement 1
Sex-specific analysis of motivation and compulsivity in vulnerable and resilient rats.
Motivation (A) and compulsivity (B) for the vulnerable and resilient populations split by sex.
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Figure 3—figure supplement 1—source data 1
Raw data utilized for generating Figure 3—figure supplement 1.
Motivation (A) and compulsivity (B) by the vulnerable and resilient populations and by sex.
- https://cdn.elifesciences.org/articles/90422/elife-90422-fig3-figsupp1-data1-v1.xlsx
Figure 4 with 1 supplement
Normalizing and combining addiction-like behaviors into an addiction index.
(A) Z-score for escalation (N=566), (B) motivation (N=512), (C) compulsivity (N=567), and (D) irritability-like behavior (N=380) in the whole population. (E) Representation of the individual rats …
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Figure 4—source data 1
Raw data utilized for generating Figure 4.
(A) Z-score for escalation (N=566), (B) motivation (N=512), (C) compulsivity (N=567), and (D) irritability-like behavior (N=380) in the whole population. (E) Combination of A-D and split on vulnerability for PCA analysis with labeling. (F) Combination of A-D, the addiction index and split on vulnerability.
- https://cdn.elifesciences.org/articles/90422/elife-90422-fig4-data1-v1.xlsx
Figure 4—figure supplement 1
Additional principal component analysis (PCA) analysis with the representation of the individual rats (N=377) along the first two principal components.
(A) Rerun the PCA from Figure 4E without irritability shows escalation, motivation, and compulsivity loading onto the first PC that explains a significant portion of the variance. (B) The same PCA …
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Figure 4—figure supplement 1—source data 1
Raw data utilized for generating Figure 4—figure supplement 1.
Principal component analysis (PCA) analyses are split by panel.
- https://cdn.elifesciences.org/articles/90422/elife-90422-fig4-figsupp1-data1-v1.xlsx
Figure 5
Different degrees of vulnerability to cocaine addictive behaviors.
(A) Cocaine infusions during short (2 hr, short access: ShA) and long (6 hr, long access: LgA) access of cocaine self-administration (N=128 Low + 128 Mild + 127 Moderate + 128 Severe; ***p<0.0001). …
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Figure 5—source data 1
Raw data utilized for generating Figure 5.
Groups split by addiction index. ‘Rat info Raw data’ tab contains the raw data table with all data analyzed, other tabs have the data split per panel in the figure as indicated. (A) Number of cocaine infusions per hour of cocaine self-administration during short (2 hr, short access: ShA) and long (6 hr, long access: LgA) access, quartered by addiction index (N=128 Low + 128 Mild + 127 Moderate + 128 Severe). (B) Average number of daily infusions for the last 3 days of LgA. (C) Number of cocaine infusions under progressive ratio (PR) tested after ShA or LgA (period). (D) Number of infusions despite footshock after LgA.
- https://cdn.elifesciences.org/articles/90422/elife-90422-fig5-data1-v1.xlsx
Author response image 1
Tables
Author response table 1
| PC1 | PC2 | |
|---|---|---|
| Escalation Index | 0.605 | -0.089 |
| Motivation Index | 0.594 | -0.071 |
| Compulsivity Index | 0.524 | 0.020 |
| Irritability Index | 0.086 | 0.993 |
