, Volume 235, Issue 4, pp 1179–1189 | Cite as

Intravenous cocaine self-administration in a panel of inbred mouse strains differing in acute locomotor sensitivity to cocaine

  • Amanda J. Roberts
  • Linzy Casal
  • Salvador Huitron-Resendiz
  • Trey Thompson
  • Lisa M. Tarantino
Original Investigation



Initial sensitivity to drugs of abuse often predicts subsequent use and abuse, but this relationship is not always observed in human studies. Moreover, studies examining the relationship between initial locomotor sensitivity and the rewarding and reinforcing effects of drugs in animal models have also been equivocal. Understanding the relationship between initial drug effects and propensity to continue use, potentially resulting in the development of a substance use disorder, may help to identify key targets for prevention and treatment.


We examined intravenous cocaine self-administration in a set of mouse strains that were previously identified to be at the phenotypic extremes for cocaine-induced locomotor activation to determine if initial locomotor sensitivity predicted acquisition, extinction, dose response, or progressive ratio (PR) breakpoint.


We selected eight inbred mouse strains based on locomotor sensitivity to 20 mg/kg cocaine. These strains, designated as low and high responders, were tested in an intravenous self-administration paradigm that included acquisition of 0.5 mg/(kg*inf) under a FR1 schedule, extinction, re-acquisition, dose response to 0.125, 0.25, 0.5, 1, and 2 mg/(kg*inf), and progressive ratio.


We observed overall differences in self-administration behavior between high and low responders. Low responders self-administered less cocaine and had lower breakpoints under the PR schedule. However, we also observed strain differences within each group. Self-administration in the low responder, LG/J, more closely resembled the behavior of the high-responding group, and the high responder, P/J, had self-administration behavior that more closely resembled the low-responding group.


We conclude that acute cocaine-induced locomotor activation does predict self-administration behavior, but in a strain-specific manner. These data support the idea that genetic background influences the relationship among addiction-related behaviors.


Cocaine Inbred mice Locomotor sensitivity Intravenous self-administration 


Funding statement

The work described in this manuscript was funded by a grant from the National Institute on Drug Abuse, R01DA023690.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

213_2018_4834_Fig7_ESM.gif (11 kb)
Supplemental Figure 1

Cocaine-induced locomotor activation dose response for saline control, 30 and 40 mg/kg. Asterisks indicate significant difference from C57BL/6 J at the same dose. Error bars are SEM. (GIF 10 kb)

213_2018_4834_MOESM1_ESM.eps (122 kb)
High resolution image (EPS 122 kb)
213_2018_4834_Fig8_ESM.gif (16 kb)
Supplemental Figure 2

Number of inactive lever presses (A) and time out responding (B) during the last day of extinction (“D10”) and the final day of re-acquisition (“R”). Data points are individual animals and error bars are SEM. (C) Number of infusions self-administered on the last day of acquisition and during reacquisition. Each data point is a strain mean. (GIF 15 kb)

213_2018_4834_MOESM2_ESM.eps (278 kb)
High resolution image (EPS 277 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Animal Models Core Facility, The Scripps Research InstituteLa JollaUSA
  2. 2.Neurosurgery and Behavior, Allen Institute for Brain ScienceSeattleUSA
  3. 3.Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of PharmacyUniversity of North CarolinaChapel HillUSA
  4. 4.Department of Genetics, School of MedicineUniversity of North CarolinaChapel HillUSA

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