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Less is more: prolonged intermittent access cocaine self-administration produces incentive-sensitization and addiction-like behavior

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Abstract

Rationale

Contemporary animal models of cocaine addiction focus on increasing the amount of drug consumption to produce addiction-like behavior. However, another critical factor is the temporal pattern of consumption, which in humans is characterized by intermittency, both within and between bouts of use.

Objective

To model this, we combined prolonged access to cocaine (∼70 days in total) with an intermittent access (IntA) self-administration procedure and used behavioral economic indicators to quantify changes in motivation for cocaine.

Results

IntA produced escalation of intake, a progressive increase in cocaine demand (incentive-sensitization), and robust drug- and cue-induced reinstatement of drug-seeking behavior. We also asked whether rats that vary in their propensity to attribute incentive salience to reward cues (sign-trackers [STs] vs. goal-trackers [GTs]) vary in the development of addiction-like behavior. Although STs were more motivated to take cocaine after limited drug experience, after IntA, STs and GTs no longer differed on any measure of addiction-like behavior.

Conclusions

Exposure to large quantities of cocaine is not necessary for escalation of intake, incentive-sensitization, or other addiction-like behaviors (IntA results in far less total cocaine consumption than ‘long access’ procedures). Also, the ST phenotype may increase susceptibility to addiction, not because STs are inherently susceptible to incentive-sensitization (perhaps all individuals are at risk), but because this phenotype promotes continued drug use, subjecting them to incentive-sensitization. Thus, the pharmacokinetics associated with the IntA procedure are especially effective in producing a number of addiction-like behaviors and may be valuable for studying associated neuroadaptations and for assessing individual variation in vulnerability.

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Acknowledgments

We thank Kent Berridge, Shelly Flagel, and Ben Saunders for their helpful comments on an earlier draft. We would also like to thank and acknowledge Dave Roberts and his students and colleagues for developing the IntA self-administration procedure, which inspired us to conduct this study.

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Authors and Affiliations

  1. Department of Psychology (Biopsychology Program), University of Michigan, 530 Church Street, East Hall, Ann Arbor, MI, 48109, USA

    Alex B. Kawa & Terry E. Robinson

  2. Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA

    Brandon S. Bentzley

Authors
  1. Alex B. Kawa
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  2. Brandon S. Bentzley
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  3. Terry E. Robinson
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Corresponding author

Correspondence to Terry E. Robinson.

Ethics declarations

All procedures were approved by the University of Michigan Committee on the Use and Care of Animals (UCUCA).

Funding

This research was supported by grants PO1 DA031656 and T32 DA007281 from NIDA.

Conflict of interest

The authors declare that they have no conflict of interest.

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Kawa, A.B., Bentzley, B.S. & Robinson, T.E. Less is more: prolonged intermittent access cocaine self-administration produces incentive-sensitization and addiction-like behavior. Psychopharmacology 233, 3587–3602 (2016). https://doi.org/10.1007/s00213-016-4393-8

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  • DOI: https://doi.org/10.1007/s00213-016-4393-8

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