High impulsivity predicts the switch to compulsive cocaine-taking.
paper
Cited
Public
Unavailable
- Authors
- Belin, David; Mar, Adam C; Dalley, Jeffrey W; Robbins, Trevor W; Everitt, Barry J
- Year
- 2008
- Journal
- Science (New York, N.Y.)
- PMID
- 18535246
- DOI
- 10.1126/science.1158136
- PMCID
- PMC2478705
Both impulsivity and novelty-seeking have been suggested to be behavioral markers of the propensity to take addictive drugs. However, their relevance for the vulnerability to compulsively seek and take drugs, which is a hallmark feature of addiction, is unknown. We report here that, whereas high reactivity to novelty predicts the propensity to initiate cocaine self-administration, high impulsivity predicts the development of addiction-like behavior in rats, including persistent or compulsive drug-taking in the face of aversive outcomes. This study shows experimental evidence that a shift from impulsivity to compulsivity occurs during the development of addictive behavior, which provides insights into the genesis and neural mechanisms of drug addiction.
Impulsivity and novelty-induced locomotor activity: two distinct phenotypesA-B. During long ITI sessions in the 5-CSRTT, HI rats showed more premature responses than LI rats [Group: F3,36 = 14.4, p < 0.01, Schedule: F8,288 = 130.22, p < 0.01, Schedule Γ Group: F24, 288 = 7.01, p < 0.01] (***: p < 0.001) (A) and HR (p < 0.01) or LR rats (p < 0.05) (B). HR rats did not differ from LR rats nor from LI subjects (B). C-D. HR rats were more reactive to novelty than LR rats [first 30 min (left histogram) or total duration of the session (right histogram): Group: F3,35 = 12.17, p < 0.01, F3,35 = 17.63, p < 0.01, respectively, Group Γ Time: F6,70 = 1.26, ns and F30,350 < 1, respectively], (p < 0.001). HI and LI subjects differed from both HR (p < 0.01) and LR rats (# p < 0.01) but never from each other. * versus HR, p < 0.05, ** p < 0.01, *** p < 0.01. Black and grey dotted lines represent the average premature responses during the last two long inter-trial intervals for HI and LI rats, respectively.
Novelty-induced locomotor activity predicts the propensity to acquire cocaine SAA. HR rats showed an upward shift of the cocaine dose-response curve compared to LR littermates [Group: F1, 16 = 4.9, p < 0.05, Dose: F6, 96 = 11.73, p < 0.01, and Group Γ Dose: F6, 96 = 4.39, p < 0.01], HR rats infusing more cocaine at the lowest three doses than vehicle (p < 0.01). B. HI and LI subjects did not differ in their number of cocaine infusions self-administered [Group: F1,16 < 1, Dose: F6, 96 = 10.79, p < 0.01, Group Γ Dose: F6, 96<1].
Highly impulsive rats closely resemble 3 criteria ratsAfter protracted self-administration 0, 1, 2 or 3 criteria rats were identified. A. When ranked on a linear addiction scale [R2 = 0.99, Group: F3,19 = 34.43, p < 0.01], 3 criteria rats had addiction scores (2.8 Β± 0.6) above the standard deviation (2.1), and higher than all the other groups (vs 0 and 1 criteria rats: Β€ p < 0.01, vs 2 criteria rats: # p β€ 0.05). B. HI rats displayed higher addiction scores than LI rats [F1,9 = 7.55, p < 0.05: *] whereas HR did not differ from LR rats. Only HI rats did not differ from 3 criteria rats for their addiction score [F5,30 = 10.13, p < 0.01], displaying higher addiction scores than 0 criteria (p < 0.01), and HR rats (p < 0.05). HR, LR and LI rats did not differ from 0 criteria rats.
Impulsivity predicts the transition to compulsivityHI rats (n = 5) displayed higher resistance to punishment than LI rats (n = 6) [F1, 9 = 12.79, p < 0.01] whereas HR (n = 5) rats did not differ from LR rats (n = 5). When compared to 0 and 3 criteria rats for their resistance to punishment [Group: F5,30 = 10.13, p < 0.01], only HI rats were similar to 3 criteria rats, showing greater resistance to punishment than 0 criteria, LI and HR rats (p < 0.05). LI and HR rats differed from 3 criteria but not from 0 criteria rats (A). **p < 0.01. B. Impulsivity predicts compulsive cocaine self-administration (R=0.42, p<0.05). Grey and black shadings represent LI and HI rats, respectively.
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