Advertisement

Psychopharmacology

, Volume 233, Issue 17, pp 3173–3186 | Cite as

Maladaptive choices by defeated rats: link between rapid approach to social threat and escalated cocaine self-administration

  • Christopher O. Boyson
  • Elizabeth N. Holly
  • Andrew R. Burke
  • Sandra Montagud-Romero
  • Joseph F. DeBold
  • Klaus A. MiczekEmail author
Original Investigation

Abstract

Rationale

Intermittent social defeat stress engenders persistent neuroadaptations and can result in later increased cocaine taking and seeking. However, there are individual differences in stress-escalated cocaine self-administration behavior, which may be a direct result of individual differences in the manner in which rats experience social defeat stress.

Objective

The present study dissected the discrete behavioral phases of social defeat and analyzed which behavioral characteristics may be predictive of subsequent cocaine self-administration.

Methods

Male Long-Evans rats underwent nine intermittent social defeat episodes over 21 days in a three-compartment apparatus permitting approach to and escape from a confrontation with an aggressive resident rat. Rats then self-administered intravenous cocaine, which culminated in a 24-h unlimited access “binge.” Behaviors during social defeat and cocaine self-administration were evaluated by principal component analysis (PCA).

Results

PCA revealed that the latency to enter the threatening environment was highly predictive of later cocaine self-administration during the 24-h binge. This behavior was not associated with other cocaine-predictive traits, such as reactivity to novelty in an open field, saccharin preference, and motor impulsivity. Additionally, there was no effect of latency to enter a threatening environment on physiological measures of stress, including plasma corticosterone and corticotropin releasing factor (CRF) in the extended amygdala. However, latency to enter the threatening environment was negatively correlated with brain-derived neurotropic factor (BDNF) and its receptor, tyrosine kinase B (TrkB) in the hippocampus.

Conclusion

These data suggest that latency to enter a threatening environment is a novel behavioral characteristic predictive of later cocaine self-administration.

Keywords

Social defeat stress Cocaine self-administration BDNF Impulsivity Behavior Individual differences 

Notes

Compliance with ethical standards

Conflicts of interest

All authors declare no conflicts of interest.

Supplementary material

213_2016_4363_MOESM1_ESM.docx (134 kb)
ESM 1 (DOCX 133 kb)

References

  1. Bardo MT, Neisewander JL, Kelly TH (2013) Individual differences and social influences on the neurobehavioral pharmacology of abused drugs. Pharmacol Rev 65:255–90CrossRefPubMedPubMedCentralGoogle Scholar
  2. Belin D, Mar AC, Dalley JW, Robbins TW, Everitt BJ (2008) High impulsivity predicts the switch to compulsive cocaine-taking. Science 320:1352–5CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bergstrom A, Jayatissa MN, Mork A, Wiborg O (2008) Stress sensitivity and resilience in the chronic mild stress rat model of depression; an in situ hybridization study. Brain Res 1196:41–52CrossRefPubMedGoogle Scholar
  4. Blanchard MM, Mendelsohn D, Stamp JA (2009) The HR/LR model: further evidence as an animal model of sensation seeking. Neurosci Biobehav Rev 33:1145–54CrossRefPubMedGoogle Scholar
  5. Boyson CO, Holly EN, Shimamoto A, Albrechet-Souza L, Weiner LA, DeBold JF, Miczek KA (2014) Social stress and CRF-dopamine interactions in the VTA: role in long-term escalation of cocaine self-administration. J Neurosci 34:6659–67CrossRefPubMedPubMedCentralGoogle Scholar
  6. Carroll ME, Morgan AD, Lynch WJ, Campbell UC, Dess NK (2002) Intravenous cocaine and heroin self-administration in rats selectively bred for differential saccharin intake: phenotype and sex differences. Psychopharmacology (Berl) 161:304–13CrossRefGoogle Scholar
  7. Cordeira JW, Frank L, Sena-Esteves M, Pothos EN, Rios M (2010) Brain-derived neurotrophic factor regulates hedonic feeding by acting on the mesolimbic dopamine system. J Neurosci 30:2533–41CrossRefPubMedPubMedCentralGoogle Scholar
  8. Covington HE 3rd, Miczek KA (2001) Repeated social-defeat stress, cocaine or morphine. Effects on behavioral sensitization and intravenous cocaine self-administration “binges”. Psychopharmacology (Berl) 158:388–98CrossRefGoogle Scholar
  9. Covington HE 3rd, Miczek KA (2005) Intense cocaine self-administration after episodic social defeat stress, but not after aggressive behavior: dissociation from corticosterone activation. Psychopharmacology (Berl) 183:331–40CrossRefGoogle Scholar
  10. Covington HE 3rd, Tropea TF, Rajadhyaksha AM, Kosofsky BE, Miczek KA (2008) NMDA receptors in the rat VTA: a critical site for social stress to intensify cocaine taking. Psychopharmacology (Berl) 197:203–16CrossRefGoogle Scholar
  11. Deroche-Gamonet V, Belin D, Piazza PV (2004) Evidence for addiction-like behavior in the rat. Science 305:1014–7CrossRefPubMedGoogle Scholar
  12. Duclot F, Kabbaj M (2013) Individual differences in novelty seeking predict subsequent vulnerability to social defeat through a differential epigenetic regulation of brain-derived neurotrophic factor expression. J Neurosci 33:11048–60CrossRefPubMedPubMedCentralGoogle Scholar
  13. Fortin DA, Srivastava T, Dwarakanath D, Pierre P, Nygaard S, Derkach VA, Soderling TR (2012) Brain-derived neurotrophic factor activation of CaM-kinase kinase via transient receptor potential canonical channels induces the translation and synaptic incorporation of GluA1-containing calcium-permeable AMPA receptors. J Neurosci 32:8127–37CrossRefPubMedPubMedCentralGoogle Scholar
  14. Haenisch B, Bilkei-Gorzo A, Caron MG, Bonisch H (2009) Knockout of the norepinephrine transporter and pharmacologically diverse antidepressants prevent behavioral and brain neurotrophin alterations in two chronic stress models of depression. J Neurochem 111:403–16CrossRefPubMedPubMedCentralGoogle Scholar
  15. Hamidovic A, Childs E, Conrad M, King A, de Wit H (2010) Stress-induced changes in mood and cortisol release predict mood effects of amphetamine. Drug Alcohol Depend 109:175–80CrossRefPubMedPubMedCentralGoogle Scholar
  16. Helms CM, Gubner NR, Wilhelm CJ, Mitchell SH, Grandy DK (2008) D4 receptor deficiency in mice has limited effects on impulsivity and novelty seeking. Pharmacol Biochem Behav 90:387–93CrossRefPubMedPubMedCentralGoogle Scholar
  17. Holly EN, Boyson CO, Montagud-Romero S, Stein DJ, Gobrogge KL, DeBold JF, Miczek KA (2016) Episodic social stress-escalated cocaine self-administration: role of phasic and tonic corticotropin releasing factor in the anterior and posterior ventral tegmental area. J Neurosci 36:4093–105CrossRefPubMedGoogle Scholar
  18. Kabbaj M, Norton CS, Kollack-Walker S, Watson SJ, Robinson TE, Akil H (2001) Social defeat alters the acquisition of cocaine self-administration in rats: role of individual differences in cocaine-taking behavior. Psychopharmacology (Berl) 158:382–7CrossRefGoogle Scholar
  19. Komatsu H, Ohara A, Sasaki K, Abe H, Hattori H, Hall FS, Uhl GR, Sora I (2011) Decreased response to social defeat stress in mu-opioid-receptor knockout mice. Pharmacol Biochem Behav 99:676–82CrossRefPubMedPubMedCentralGoogle Scholar
  20. Koolhaas JM, de Boer SF, Coppens CM, Buwalda B (2010) Neuroendocrinology of coping styles: towards understanding the biology of individual variation. Front Neuroendocrinol 31:307–21CrossRefPubMedGoogle Scholar
  21. Madara JC, Levine ES (2008) Presynaptic and postsynaptic NMDA receptors mediate distinct effects of brain-derived neurotrophic factor on synaptic transmission. J Neurophysiol 100:3175–84CrossRefPubMedPubMedCentralGoogle Scholar
  22. McEwen BS (1999) Stress and hippocampal plasticity. Annu Rev Neurosci 22:105–22CrossRefPubMedGoogle Scholar
  23. Miczek KA, Mutschler NH (1996) Activational effects of social stress on IV cocaine self-administration in rats. Psychopharmacology (Berl) 128:256–64CrossRefGoogle Scholar
  24. Miczek KA, Nikulina EM, Shimamoto A, Covington HE 3rd (2011) Escalated or suppressed cocaine reward, tegmental BDNF, and accumbal dopamine caused by episodic versus continuous social stress in rats. J Neurosci 31:9848–57CrossRefPubMedPubMedCentralGoogle Scholar
  25. Murray JE, Dilleen R, Pelloux Y, Economidou D, Dalley JW, Belin D, Everitt BJ (2014) Increased impulsivity retards the transition to dorsolateral striatal dopamine control of cocaine seeking. Biol Psychiatry 76:15–22CrossRefPubMedPubMedCentralGoogle Scholar
  26. National Research Council (2011) Guide for the care and use of laboratory animals, 8th edn. The National Academies Press, WashingtonGoogle Scholar
  27. Park H, Poo MM (2013) Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci 14:7–23CrossRefPubMedGoogle Scholar
  28. Patki G, Solanki N, Atrooz F, Allam F, Salim S (2013) Depression, anxiety-like behavior and memory impairment are associated with increased oxidative stress and inflammation in a rat model of social stress. Brain Res 1539:73–86CrossRefPubMedPubMedCentralGoogle Scholar
  29. Piazza PV, Deminiere JM, Le Moal M, Simon H (1989) Factors that predict individual vulnerability to amphetamine self-administration. Science 245:1511–3CrossRefPubMedGoogle Scholar
  30. Shimamoto A, Holly EN, Boyson CO, DeBold JF, Miczek KA (2015) Individual differences in anhedonic and accumbal dopamine responses to chronic social stress and their link to cocaine self-administration in female rats. Psychopharmacology (Berl) 232:825–34CrossRefGoogle Scholar
  31. Sinha R (2001) How does stress increase risk of drug abuse and relapse? Psychopharmacology (Berl) 158:343–59CrossRefGoogle Scholar
  32. Swanson LW, Sawchenko PE, Rivier J, Vale WW (1983) Organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinology 36:165–86CrossRefPubMedGoogle Scholar
  33. Taliaz D, Loya A, Gersner R, Haramati S, Chen A, Zangen A (2011) Resilience to chronic stress is mediated by hippocampal brain-derived neurotrophic factor. J Neurosci 31:4475–83CrossRefPubMedGoogle Scholar
  34. Tidey JW, Miczek KA (1997) Acquisition of cocaine self-administration after social stress: role of accumbens dopamine. Psychopharmacology (Berl) 130:203–12CrossRefGoogle Scholar
  35. Wood SK, Walker HE, Valentino RJ, Bhatnagar S (2010) Individual differences in reactivity to social stress predict susceptibility and resilience to a depressive phenotype: role of corticotropin-releasing factor. Endocrinology 151:1795–805CrossRefPubMedPubMedCentralGoogle Scholar
  36. Zhang JC, Yao W, Dong C, Yang C, Ren Q, Ma M, Han M, Hashimoto K (2015) Comparison of ketamine, 7,8-dihydroxyflavone, and ANA-12 antidepressant effects in the social defeat stress model of depression. Psychopharmacology (Berl) 232:4325–35CrossRefGoogle Scholar
  37. Zorrilla EP, Logrip ML, Koob GF (2014) Corticotropin releasing factor: a key role in the neurobiology of addiction. Front Neuroendocrinol 35:234–44CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Christopher O. Boyson
    • 1
  • Elizabeth N. Holly
    • 1
    • 2
    • 3
    • 4
  • Andrew R. Burke
    • 1
    • 5
  • Sandra Montagud-Romero
    • 1
    • 6
  • Joseph F. DeBold
    • 1
  • Klaus A. Miczek
    • 1
    • 7
    • 8
    • 9
    Email author
  1. 1.Department of PsychologyTufts UniversityMedfordUSA
  2. 2.McGovern Institute for Brain ResearchMassachusetts Institute of TechnologyCambridgeUSA
  3. 3.Department of Brain and Cognitive SciencesMassachusetts Institute of TechnologyCambridgeUSA
  4. 4.Current affiliation: Department of Neuroscience, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  5. 5.Current affiliation: Department of PsychiatryIndiana University School of MedicineIndianapolisUSA
  6. 6.Unidad de Investigación Psicobiología de las Drogodependencias, Departmento de PsicobiologíaUniversitat de ValènciaValènciaSpain
  7. 7.Department of PsychiatryTufts University School of MedicineBostonUSA
  8. 8.Department of PharmacologyTufts University School of MedicineBostonUSA
  9. 9.Department of NeuroscienceTufts University School of MedicineBostonUSA

Personalised recommendations