Intravenous cocaine self-administration in a panel of inbred mouse strains differing in acute locomotor sensitivity to cocaine
- 31 Downloads
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.
KeywordsCocaine Inbred mice Locomotor sensitivity Intravenous self-administration
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
- Ahmari SE (2016) Using mice to model obsessive compulsive disorder: from genes to circuits. Neuroscience 321:121–137. https://doi.org/10.1016/j.neuroscience.2015.11.009 CrossRefPubMedGoogle Scholar
- (CASA), National Ctr on Addiction and Substance Abuse at Columbia University (2009) Shoveling up II: the impact of substance abuse on federal, state and local budgets. Columbia University, New YorkGoogle Scholar
- Churchill GA, Airey DC, Allayee H, Angel JM, Attie AD, Beatty J, . . . Complex Trait, Consortium (2004) The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nat Genet, 36(11):1133–1137. https://doi.org/10.1038/ng1104-1133
- Contet C, Whisler KN, Jarrell H, Kenny PJ, Markou A (2010) Patterns of responding differentiate intravenous nicotine self-administration from responding for a visual stimulus in C57BL/6J mice. Psychopharmacology 212(3):283–299. https://doi.org/10.1007/s00213-010-1950-4 CrossRefPubMedPubMedCentralGoogle Scholar
- Dickson PE, Ndukum J, Wilcox T, Clark J, Roy B, Zhang L, . . . Chesler EJ (2015) Association of novelty-related behaviors and intravenous cocaine self-administration in Diversity Outbred mice. Psychopharmacology, 232(6):1011–1024. https://doi.org/10.1007/s00213-014-3737-5
- Gutierrez-Cuesta J, Burokas A, Mancino S, Kummer S, Martin-Garcia E, Maldonado R (2014) Effects of genetic deletion of endogenous opioid system components on the reinstatement of cocaine-seeking behavior in mice. Neuropsychopharmacology 39(13):2974–2988. https://doi.org/10.1038/npp.2014.149 CrossRefPubMedPubMedCentralGoogle Scholar
- Haertzen CA, Kocher TR, Miyasato K (1983) Reinforcements from the first drug experience can predict later drug habits and/or addiction: results with coffee, cigarettes, alcohol, barbiturates, minor and major tranquilizers, stimulants, marijuana, hallucinogens, heroin, opiates and cocaine. Drug Alcohol Depend 11(2):147–165. https://doi.org/10.1016/0376-8716(83)90076-5 CrossRefPubMedGoogle Scholar
- Kumar V, Kim K, Joseph C, Kourrich S, Yoo SH, Huang HC, Vitaterna MH, Pardo-Manuel de Villena F, Churchill G, Bonci A, Takahashi JS (2013) C57BL/6N mutation in cytoplasmic FMRP interacting protein 2 regulates cocaine response. Science 342(6165):1508–1512. https://doi.org/10.1126/science.1245503 CrossRefPubMedPubMedCentralGoogle Scholar
- Mandt BH, Johnston NL, Zahniser NR, Allen RM (2012) Acquisition of cocaine self-administration in male Sprague-Dawley rats: effects of cocaine dose but not initial locomotor response to cocaine. Psychopharmacology 219(4):1089–1097. https://doi.org/10.1007/s00213-011-2438-6 CrossRefPubMedGoogle Scholar
- Miller T, Hendrie D (2008) Substance abuse prevention dollars and cents: a cost-benefit analysis. ((SMA) 07-4298). RockvilleGoogle Scholar
- Paneda C, Huitron-Resendiz S, Frago LM, Chowen JA, Picetti R, de Lecea L, Roberts AJ (2009) Neuropeptide S reinstates cocaine-seeking behavior and increases locomotor activity through corticotropin-releasing factor receptor 1 in mice. J Neurosci 29(13):4155–4161. https://doi.org/10.1523/JNEUROSCI.5256-08.2009 CrossRefPubMedPubMedCentralGoogle Scholar
- Parker CC, Chen H, Flagel SB, Geurts AM, Richards JB, Robinson TE . . ., Palmer AA (2014). Rats are the smart choice: rationale for a renewed focus on rats in behavioral genetics. Neuropharmacology 76 Pt B:250-258. https://doi.org/10.1016/j.neuropharm.2013.05.047
- Roberts AJ, Polis IY, Gold LH (1997) Intravenous self-administration of heroin, cocaine, and the combination in Balb/c mice. European Journal of Pharmacology, 326(2-3), 119-125. Doi. https://doi.org/10.1016/S0014-2999(97)85405-2
- Thanos PK, Subrize M, Lui W, Puca Z, Ananth M, Michaelides M, . . . Volkow ND (2011) D-cycloserine facilitates extinction of cocaine self-administration in C57 mice. Synapse 65(10):1099–1105. https://doi.org/10.1002/syn.20944
- Ward SJ, Rosenberg M, Dykstra LA, Walker EA (2009) The CB1 antagonist rimonabant (SR141716) blocks cue-induced reinstatement of cocaine seeking and other context and extinction phenomena predictive of relapse. Drug Alcohol Depend 105(3):248–255. https://doi.org/10.1016/j.drugalcdep.2009.07.002 CrossRefPubMedPubMedCentralGoogle Scholar
- Wiltshire T, Ervin RB, Duan H, Bogue MA, Zamboni WC, Cook S, . . . Tarantino LM (2015) Initial locomotor sensitivity to cocaine varies widely among inbred mouse strains. Genes Brain Behav 14(3): 271–280. https://doi.org/10.1111/gbb.12209
- Yamamoto DJ, Nelson AM, Mandt BH, Larson GA, Rorabaugh JM, Ng CM, . . . Zahniser NR (2013). Rats classified as low or high cocaine locomotor responders: a unique model involving striatal dopamine transporters that predicts cocaine addiction-like behaviors. Neurosci Biobehav Rev 37(8):1738–1753. https://doi.org/10.1016/j.neubiorev.2013.07.002
- Yan Y, Nitta A, Mizoguchi H, Yamada K, Nabeshima T (2006) Relapse of methamphetamine-seeking behavior in C57BL/6J mice demonstrated by a reinstatement procedure involving intravenous self-administration. Behav Brain Res 168(1):137–143. https://doi.org/10.1016/j.bbr.2005.11.030 CrossRefPubMedGoogle Scholar
- Yazdani N, Parker CC, Shen Y, Reed ER, Guido MA, Kole LA, . . . Bryant CD (2015) Hnrnph1 is a quantitative trait gene for methamphetamine sensitivity. PLoS Genet 11(12): e1005713. https://doi.org/10.1371/journal.pgen.1005713