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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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Related in: MedlinePlus

Amphetamine potentiates CR, but not NCR, lever presses in both the 5- and 90-s groups.Presses on the CR and NCR levers following an acute injection of saline (panel A), 0.25 (panel B) and 0.5 (panel C) mg/kg amphetamine. Values are mean ± SEM. n's = 5/group. s, seconds; CR, conditioned reward lever; NCR, non-conditioned reward lever; AMPH, amphetamine. *p<0.05 compared with NCR within the same group. α p<0.05 compared with CR under saline.
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pone-0026481-g004: Amphetamine potentiates CR, but not NCR, lever presses in both the 5- and 90-s groups.Presses on the CR and NCR levers following an acute injection of saline (panel A), 0.25 (panel B) and 0.5 (panel C) mg/kg amphetamine. Values are mean ± SEM. n's = 5/group. s, seconds; CR, conditioned reward lever; NCR, non-conditioned reward lever; AMPH, amphetamine. *p<0.05 compared with NCR within the same group. α p<0.05 compared with CR under saline.

Mentions: Figure 4 shows CR versus NCR lever presses as a function of group, following an injection of saline (A), 0.25 (B) and 0.5 (C) mg/kg AMPH. There was no main effect of group (F(1, 8) = 0.337, p = 0.58). There was a significant main effect of lever (F(1, 8) = 14.72, p = 0.005). Further investigation of the effect of lever revealed that in the 5-s group, CR lever presses were greater than NCR lever presses following an injection of 0.25 mg/kg AMPH [(B) t(4) = 3.63, p = 0.02], but not following saline [(A) t(4) = 0.70, p = 0.52] or an injection of 0.5 mg/kg AMPH [(C) t(4) = 1.95, p = 0.12]. For the 90-s group, CR lever presses were greater than NCR lever presses following an injection of either 0.25 mg/kg [(B) t(4) = 3.48, p = 0.025] or 0.5 mg/kg AMPH [(C) t(4) = 2.97, p = 0.041], but not following an injection of saline [(A) t(4) = 2.87, p = 0.05]. Thus, both groups showed no lever discrimination following an injection of saline, but pressed more on the CR vs. NCR lever following an acute AMPH challenge. In addition, there was a significant lever x AMPH dose interaction (F(1, 8) = 9.67, p = 0.014), indicating that the effect of AMPH on lever pressing depended on lever type. To investigate the lever x AMPH dose interaction, we collapsed the 5- and 90-s groups together and used Helmert contrasts to compare saline to the two AMPH doses and the two AMPH doses to each other. This confirmed that both 0.25 and 0.5 mg/kg AMPH increased CR lever pressing relative to saline (F(1, 9) = 14.293, p = 0.004), and that there was no difference between the two AMPH doses (F(1, 9) = 1.41, p = 0.27).


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)

Amphetamine potentiates CR, but not NCR, lever presses in both the 5- and 90-s groups.Presses on the CR and NCR levers following an acute injection of saline (panel A), 0.25 (panel B) and 0.5 (panel C) mg/kg amphetamine. Values are mean ± SEM. n's = 5/group. s, seconds; CR, conditioned reward lever; NCR, non-conditioned reward lever; AMPH, amphetamine. *p<0.05 compared with NCR within the same group. α p<0.05 compared with CR under saline.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3198427&req=5

pone-0026481-g004: Amphetamine potentiates CR, but not NCR, lever presses in both the 5- and 90-s groups.Presses on the CR and NCR levers following an acute injection of saline (panel A), 0.25 (panel B) and 0.5 (panel C) mg/kg amphetamine. Values are mean ± SEM. n's = 5/group. s, seconds; CR, conditioned reward lever; NCR, non-conditioned reward lever; AMPH, amphetamine. *p<0.05 compared with NCR within the same group. α p<0.05 compared with CR under saline.
Mentions: Figure 4 shows CR versus NCR lever presses as a function of group, following an injection of saline (A), 0.25 (B) and 0.5 (C) mg/kg AMPH. There was no main effect of group (F(1, 8) = 0.337, p = 0.58). There was a significant main effect of lever (F(1, 8) = 14.72, p = 0.005). Further investigation of the effect of lever revealed that in the 5-s group, CR lever presses were greater than NCR lever presses following an injection of 0.25 mg/kg AMPH [(B) t(4) = 3.63, p = 0.02], but not following saline [(A) t(4) = 0.70, p = 0.52] or an injection of 0.5 mg/kg AMPH [(C) t(4) = 1.95, p = 0.12]. For the 90-s group, CR lever presses were greater than NCR lever presses following an injection of either 0.25 mg/kg [(B) t(4) = 3.48, p = 0.025] or 0.5 mg/kg AMPH [(C) t(4) = 2.97, p = 0.041], but not following an injection of saline [(A) t(4) = 2.87, p = 0.05]. Thus, both groups showed no lever discrimination following an injection of saline, but pressed more on the CR vs. NCR lever following an acute AMPH challenge. In addition, there was a significant lever x AMPH dose interaction (F(1, 8) = 9.67, p = 0.014), indicating that the effect of AMPH on lever pressing depended on lever type. To investigate the lever x AMPH dose interaction, we collapsed the 5- and 90-s groups together and used Helmert contrasts to compare saline to the two AMPH doses and the two AMPH doses to each other. This confirmed that both 0.25 and 0.5 mg/kg AMPH increased CR lever pressing relative to saline (F(1, 9) = 14.293, p = 0.004), and that there was no difference between the two AMPH doses (F(1, 9) = 1.41, p = 0.27).

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