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Cues paired with either rapid or slower self-administered cocaine injections acquire similar conditioned rewarding properties.

Samaha AN, Minogianis EA, Nachar W - PLoS ONE (2011)

Bottom Line: Rats in both the 5- and 90-second groups pressed more on the active versus inactive lever following extensive (24 sessions) but not following limited (3 sessions) self-administration training.There were no group differences in this behaviour.However, the rewarding properties of the cues were not "forgotten" because on withdrawal days 32-33, amphetamine selectively enhanced active-lever pressing, and did so to a similar extent in both groups.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada. Anna.samaha@umontreal.ca

ABSTRACT
The faster drugs of abuse reach the brain, the more addictive they can be. It is not known why this is. Environmental stimuli associated with drugs can promote the development and persistence of addiction by invigorating and precipitating drug-seeking behaviour. We determined, therefore, whether cues associated with the self-administration of rapidly delivered cocaine (injected intravenously over 5 versus 90 seconds) would acquire greater conditioned rewarding properties, as assessed by the performance of an operant response reinforced solely by the cues. Rats nose-poked for intravenous cocaine infusions delivered either over 5 or 90 seconds. Discrete visual cues accompanied each infusion. The rats could then press a lever to obtain the cues--now a conditioned reward--or an inactive lever. Rats in both the 5- and 90-second groups pressed more on the active versus inactive lever following extensive (24 sessions) but not following limited (3 sessions) self-administration training. There were no group differences in this behaviour. Following withdrawal from cocaine self-administration, lever discrimination progressively abated in both groups and was lost by withdrawal day 30. However, the rewarding properties of the cues were not "forgotten" because on withdrawal days 32-33, amphetamine selectively enhanced active-lever pressing, and did so to a similar extent in both groups. Thus, cues paired with rapid or slower cocaine delivery acquire similar conditioned rewarding properties. We conclude, therefore, that the rapid delivery of cocaine to the brain promotes addiction by mechanisms that might not involve a greater ability of drug cues to control behaviour.

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A cue paired with either rapid or slower cocaine injections acquires similar conditioned rewarding properties, and these properties abate with time.Presses on the CR and NCR levers on Day 1 (panel A), Days 10–11 (panel B) and Day 30 (panel C) of withdrawal from self-administered cocaine in the 5- and 90-s groups. Values are mean ± SEM. n's = 5/group. s, seconds; CR, conditioned reward lever; NCR, non-conditioned reward lever. *p<0.05 compared with NCR within the same group.
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pone-0026481-g003: A cue paired with either rapid or slower cocaine injections acquires similar conditioned rewarding properties, and these properties abate with time.Presses on the CR and NCR levers on Day 1 (panel A), Days 10–11 (panel B) and Day 30 (panel C) of withdrawal from self-administered cocaine in the 5- and 90-s groups. Values are mean ± SEM. n's = 5/group. s, seconds; CR, conditioned reward lever; NCR, non-conditioned reward lever. *p<0.05 compared with NCR within the same group.

Mentions: Figure 3 shows CR versus NCR lever presses as a function of group, one day (A), 10–11 days (B) and 30 days (C) following the last cocaine self-administration session. There was no main effect of group (F(1, 8) = 0.012, p = 0.92). There was a significant overall main effect of lever (F(1, 8) = 10.63, p = 0.012). Further investigation of the effect of lever revealed that in the 5-s group, CR lever presses were greater than NCR lever presses on Day 1 [(A) t(4) = 2.77, p = 0.049] and on Days 10–11 [(B) t(4) = 3.07, p = 0.037], but not on Day 30 [(C) t(4) = 1.15, p = 0.31] of cocaine withdrawal. In the 90-s group, CR lever presses were greater than NCR lever presses only on Day 1 of cocaine withdrawal [(A) t(4) = 3.30, p = 0.03; (B) t(4) = 2.00, p = 0.12; (C) t(4) = 1.26, p = 0.28]. This indicates that early following withdrawal from cocaine self-administration, both groups discriminated between the two levers and spontaneously acquired a new operant response, reinforced solely by the conditioned reward. However, in both groups, lever discrimination was no longer evident following more extended withdrawal from cocaine.


Cues paired with either rapid or slower self-administered cocaine injections acquire similar conditioned rewarding properties.

Samaha AN, Minogianis EA, Nachar W - PLoS ONE (2011)

A cue paired with either rapid or slower cocaine injections acquires similar conditioned rewarding properties, and these properties abate with time.Presses on the CR and NCR levers on Day 1 (panel A), Days 10–11 (panel B) and Day 30 (panel C) of withdrawal from self-administered cocaine in the 5- and 90-s groups. Values are mean ± SEM. n's = 5/group. s, seconds; CR, conditioned reward lever; NCR, non-conditioned reward lever. *p<0.05 compared with NCR within the same group.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3198427&req=5

pone-0026481-g003: A cue paired with either rapid or slower cocaine injections acquires similar conditioned rewarding properties, and these properties abate with time.Presses on the CR and NCR levers on Day 1 (panel A), Days 10–11 (panel B) and Day 30 (panel C) of withdrawal from self-administered cocaine in the 5- and 90-s groups. Values are mean ± SEM. n's = 5/group. s, seconds; CR, conditioned reward lever; NCR, non-conditioned reward lever. *p<0.05 compared with NCR within the same group.
Mentions: Figure 3 shows CR versus NCR lever presses as a function of group, one day (A), 10–11 days (B) and 30 days (C) following the last cocaine self-administration session. There was no main effect of group (F(1, 8) = 0.012, p = 0.92). There was a significant overall main effect of lever (F(1, 8) = 10.63, p = 0.012). Further investigation of the effect of lever revealed that in the 5-s group, CR lever presses were greater than NCR lever presses on Day 1 [(A) t(4) = 2.77, p = 0.049] and on Days 10–11 [(B) t(4) = 3.07, p = 0.037], but not on Day 30 [(C) t(4) = 1.15, p = 0.31] of cocaine withdrawal. In the 90-s group, CR lever presses were greater than NCR lever presses only on Day 1 of cocaine withdrawal [(A) t(4) = 3.30, p = 0.03; (B) t(4) = 2.00, p = 0.12; (C) t(4) = 1.26, p = 0.28]. This indicates that early following withdrawal from cocaine self-administration, both groups discriminated between the two levers and spontaneously acquired a new operant response, reinforced solely by the conditioned reward. However, in both groups, lever discrimination was no longer evident following more extended withdrawal from cocaine.

Bottom Line: Rats in both the 5- and 90-second groups pressed more on the active versus inactive lever following extensive (24 sessions) but not following limited (3 sessions) self-administration training.There were no group differences in this behaviour.However, the rewarding properties of the cues were not "forgotten" because on withdrawal days 32-33, amphetamine selectively enhanced active-lever pressing, and did so to a similar extent in both groups.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada. Anna.samaha@umontreal.ca

ABSTRACT
The faster drugs of abuse reach the brain, the more addictive they can be. It is not known why this is. Environmental stimuli associated with drugs can promote the development and persistence of addiction by invigorating and precipitating drug-seeking behaviour. We determined, therefore, whether cues associated with the self-administration of rapidly delivered cocaine (injected intravenously over 5 versus 90 seconds) would acquire greater conditioned rewarding properties, as assessed by the performance of an operant response reinforced solely by the cues. Rats nose-poked for intravenous cocaine infusions delivered either over 5 or 90 seconds. Discrete visual cues accompanied each infusion. The rats could then press a lever to obtain the cues--now a conditioned reward--or an inactive lever. Rats in both the 5- and 90-second groups pressed more on the active versus inactive lever following extensive (24 sessions) but not following limited (3 sessions) self-administration training. There were no group differences in this behaviour. Following withdrawal from cocaine self-administration, lever discrimination progressively abated in both groups and was lost by withdrawal day 30. However, the rewarding properties of the cues were not "forgotten" because on withdrawal days 32-33, amphetamine selectively enhanced active-lever pressing, and did so to a similar extent in both groups. Thus, cues paired with rapid or slower cocaine delivery acquire similar conditioned rewarding properties. We conclude, therefore, that the rapid delivery of cocaine to the brain promotes addiction by mechanisms that might not involve a greater ability of drug cues to control behaviour.

Show MeSH
Related in: MedlinePlus