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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

In Experiment 1, there were no differences in the amount of cocaine exposure, cocaine-cue exposure, or number of days to reach each infusion criterion between the 5- and 90-s groups.Total drug intake (panel A), number of cue-cocaine pairings (panel B) and days to reach infusion criteria (panel C). Note that total drug intake includes cocaine taken during self-administration training, when all rats self-administered cocaine injections delivered over 5 seconds. Rats were required to meet infusion criteria 10–25 for 2 days each and infusion criterion 30 for 5 days. Values are mean ± SEM. n's = 5/group. s, seconds. CS, conditioned stimulus; UCS; unconditioned stimulus.
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pone-0026481-g002: In Experiment 1, there were no differences in the amount of cocaine exposure, cocaine-cue exposure, or number of days to reach each infusion criterion between the 5- and 90-s groups.Total drug intake (panel A), number of cue-cocaine pairings (panel B) and days to reach infusion criteria (panel C). Note that total drug intake includes cocaine taken during self-administration training, when all rats self-administered cocaine injections delivered over 5 seconds. Rats were required to meet infusion criteria 10–25 for 2 days each and infusion criterion 30 for 5 days. Values are mean ± SEM. n's = 5/group. s, seconds. CS, conditioned stimulus; UCS; unconditioned stimulus.

Mentions: All rats were first required to acquire cocaine self-administration behaviour, where each cocaine infusion was delivered over 5 s and followed by an 85-s time out period during which drug was unavailable. Rats were then divided into the 5- and 90-s groups where each self-administered cocaine infusion was delivered either over 5 or 90 s and now accompanied by a light cue. During the cocaine-cue self-administration phase, rats were required to meet a progressively increasing criterion of 10, 15, 20 and 25 infusions/session, for 2 consecutive days each, and then an infusion criterion of 30 for 5 days. Figure 2 shows the total amount of cocaine consumed (A), the total number of cue-cocaine pairings earned (B) and the number of days to reach each infusion criterion (C) by rats in the 5- and 90-s groups. Note that the total amount of cocaine consumed includes cocaine taken during training, when all rats self-administered cocaine injections delivered over 5 s. The two groups were exposed to a similar total quantity of cocaine [(A), t(8) = 0.69, p = 0.51] and total number of cue-cocaine pairings [(B), t(8) = 1.4, p = 0.20]. In addition, there were no group differences in the mean ± SEM number of days to meet each infusion criterion [(C), F(1, 8) = 0.81, p = 0.39].


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)

In Experiment 1, there were no differences in the amount of cocaine exposure, cocaine-cue exposure, or number of days to reach each infusion criterion between the 5- and 90-s groups.Total drug intake (panel A), number of cue-cocaine pairings (panel B) and days to reach infusion criteria (panel C). Note that total drug intake includes cocaine taken during self-administration training, when all rats self-administered cocaine injections delivered over 5 seconds. Rats were required to meet infusion criteria 10–25 for 2 days each and infusion criterion 30 for 5 days. Values are mean ± SEM. n's = 5/group. s, seconds. CS, conditioned stimulus; UCS; unconditioned stimulus.
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Related In: Results  -  Collection

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pone-0026481-g002: In Experiment 1, there were no differences in the amount of cocaine exposure, cocaine-cue exposure, or number of days to reach each infusion criterion between the 5- and 90-s groups.Total drug intake (panel A), number of cue-cocaine pairings (panel B) and days to reach infusion criteria (panel C). Note that total drug intake includes cocaine taken during self-administration training, when all rats self-administered cocaine injections delivered over 5 seconds. Rats were required to meet infusion criteria 10–25 for 2 days each and infusion criterion 30 for 5 days. Values are mean ± SEM. n's = 5/group. s, seconds. CS, conditioned stimulus; UCS; unconditioned stimulus.
Mentions: All rats were first required to acquire cocaine self-administration behaviour, where each cocaine infusion was delivered over 5 s and followed by an 85-s time out period during which drug was unavailable. Rats were then divided into the 5- and 90-s groups where each self-administered cocaine infusion was delivered either over 5 or 90 s and now accompanied by a light cue. During the cocaine-cue self-administration phase, rats were required to meet a progressively increasing criterion of 10, 15, 20 and 25 infusions/session, for 2 consecutive days each, and then an infusion criterion of 30 for 5 days. Figure 2 shows the total amount of cocaine consumed (A), the total number of cue-cocaine pairings earned (B) and the number of days to reach each infusion criterion (C) by rats in the 5- and 90-s groups. Note that the total amount of cocaine consumed includes cocaine taken during training, when all rats self-administered cocaine injections delivered over 5 s. The two groups were exposed to a similar total quantity of cocaine [(A), t(8) = 0.69, p = 0.51] and total number of cue-cocaine pairings [(B), t(8) = 1.4, p = 0.20]. In addition, there were no group differences in the mean ± SEM number of days to meet each infusion criterion [(C), F(1, 8) = 0.81, p = 0.39].

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