High and escalating levels of cocaine intake are dissociable from subsequent incentive motivation for the drug in rats
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Taking high and increasing amounts of cocaine is thought to be necessary for the development of addiction. Consequently, a widely used animal model of drug self-administration involves giving animals continuous drug access during long sessions (LgA), as this produces high and escalating levels of intake. However, human cocaine addicts likely use the drug with an intermittent rather than continuous pattern, producing spiking brain cocaine levels.
Using an intermittent-access (IntA) cocaine self-administration procedure in rats, we studied the relationship between escalation of cocaine intake and later incentive motivation for the drug, as measured by responding under a progressive ratio schedule of cocaine reinforcement.
First, under IntA, rats escalated their cocaine use both within and between sessions. However, escalation did not predict later incentive motivation for the drug. Second, incentive motivation for cocaine was similar in IntA-rats limited to low- and non-escalating levels of drug intake (IntA-Lim) and in IntA-rats that took high and escalating levels of drug. Finally, IntA-Lim rats took much less cocaine than rats given continuous drug access during each self-administration session (LgA-rats). However, IntA-Lim rats later responded more for cocaine under a progressive ratio schedule of reinforcement.
Taking large and escalating quantities of cocaine does not appear necessary to increase incentive motivation for the drug. Taking cocaine in an intermittent pattern—even in small amounts—is more effective in producing this addiction-relevant change. Thus, beyond the amount of drug taken, the temporal kinetics of drug use predict change in drug use over time.
KeywordsAddiction Intravenous drug self-administration Intermittent access Long access Escalation of cocaine intake Binge-like cocaine intake Progressive ratio
We are thankful to Dr. David C. S. Roberts for the scientific inspiration leading to this work and to Dr. Terry E. Robinson for wise comments on this manuscript.
F.A performed research and analyzed the data. F.A and A.N.S designed the research and wrote the paper. F.A and K.B.G wrote and tested the computer code needed to apply the IntA drug self-administration procedure to the operant conditioning cages in the laboratory.
This work was supported by grants to A.N.S from the Canadian Foundation for Innovation (grant number 24326) and the Canadian Institutes of Health Research (grant number 157572). A.N.S is supported by a salary grant from the Fonds de Recherche du Québec—Santé (grant number 28988). F.A is supported by a PhD fellowship from the Groupe de Recherche sur le Système Nerveux Central. A.N.S is a consultant for Nektar Therapeutics.
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Conflict of interest
The authors declare that they have no conflicts of interest.
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