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Intermittent access cocaine self-administration produces psychomotor sensitization: effects of withdrawal, sex and cross-sensitization

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Abstract

Rationale

With repeated administration, the psychomotor activating effects of drugs such as cocaine or amphetamine can change in very different ways—showing sensitization or tolerance—depending on whether they are administered more or less intermittently. This behavioral plasticity is thought to reflect, at least in part, changes in dopamine (DA) neurotransmission, and therefore, may provide insights into the development of substance use disorders. Indeed, the most widely used preclinical model of cocaine addiction, which involves Long Access (LgA) self-administration procedures, is reported to produce tolerance to cocaine’s psychomotor activating effects and effects on DA activity. In contrast, Intermittent Access (IntA) cocaine self-administration is more effective than LgA in producing addiction-like behavior, but sensitizes DA neurotransmission. There is, however, very little information concerning the effects of IntA experience on the psychomotor activating effects of cocaine.

Objective

The objective of this study was to determine whether IntA experience produces psychomotor sensitization with similar characteristics to that produced by the intermittent, noncontingent administration of cocaine.

Results

IntA to cocaine did indeed produce psychomotor sensitization that (1) was greater after a long (30 days) vs. short (1 day) period of withdrawal, (2) was greater in females than males, and (3) resulted in cross-sensitization to another psychomotor stimulant drug, amphetamine.

Conclusion

The tolerance sometimes associated with LgA cocaine self-administration has been cited in support of the idea that, in addiction, drug-seeking and drug-taking is motivated to overcome a DA deficiency and associated anhedonia. In contrast, the neurobehavioral sensitization associated with IntA cocaine self-administration favors an incentive-sensitization view.

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Acknowledgements

The authors thank Kendall Coden, Jack Hildenbrand, Joyce Xia, and Lauren Longyear for their contributions to data collection and/or analysis. We thank NIDA for the gift of cocaine from the NIDA drug supply program.

Funding

This research was supported by grant RO1 DA044204 from NIDA to TER and CRF and R21 DA045277 to CRF.

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Correspondence to Terry E. Robinson.

Ethics declarations

All procedures were approved by the University of Michigan Institutional Animal Care and Use Committee, in accordance with AAALAC and AVMA guidelines.

Conflict of interest

The authors declare that they have no conflict of interest.

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Carr, C.C., Ferrario, C.R. & Robinson, T.E. Intermittent access cocaine self-administration produces psychomotor sensitization: effects of withdrawal, sex and cross-sensitization. Psychopharmacology 237, 1795–1812 (2020). https://doi.org/10.1007/s00213-020-05500-4

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  • DOI: https://doi.org/10.1007/s00213-020-05500-4

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