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Unpleasant Sound Elicits Negative Emotion and Reinstates Drug Seeking

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Abstract

Although previous studies have suggested an association between unpleasant sounds and the use of drugs, scientific evidence supporting this is lacking. This study investigated in rats (male Sprague-Dawley rats) if aversive sounds modulate dopamine (DA) transmission in the mesolimbic reward system and cocaine reinforcement. For sound stimulation, we used artificial low-frequency ultrasound (ALFUS) in the frequency ranges (22–38 kHz) which produces an aversive response in rats. Rats displayed increased anxiety-like behaviors, 22-kHz ultrasonic vocalizations (USVs), and stress responses with ALFUS. In vivo extracellular recording and immunohistochemistry revealed that ALFUS stimulation activated central amygdalar neurons and amygdalar GABAergic neurons. Amygdalar lesions prevented an increase of 22-kHz USVs by ALFUS. Dopamine levels in NAc decreased during ALFUS stimulation. In rats self-administering cocaine, ALFUS caused reinstatement of cocaine seeking after a period of extinction. Thus, ALFUS stimulation induced negative emotional states in association with a decrease in mesolimbic DA function and reinstatement of cocaine-seeking behaviors, suggesting that exposure to unpleasant sounds enhances negative emotional states and may induce relapse in addicts.

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References

  1. Hamann SB, Ely TD, Hoffman JM, Kilts CD (2002) Ecstasy and agony: activation of the human amygdala in positive and negative emotion. Psychol Sci 13(2):135–141. https://doi.org/10.1111/1467-9280.00425

    Article  PubMed  Google Scholar 

  2. Kumar S, von Kriegstein K, Friston K, Griffiths TD (2012) Features versus feelings: dissociable representations of the acoustic features and valence of aversive sounds. J Neurosci 32(41):14184–14192. https://doi.org/10.1523/JNEUROSCI.1759-12.2012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Zald DH, Pardo JV (2002) The neural correlates of aversive auditory stimulation. NeuroImage 16(3 Pt 1):746–753

    Article  Google Scholar 

  4. Ompad D, Fuller C (2005) The urban environment, drug use, and health. In: Handbook of Urban Health. Springer, pp 127–154. https://doi.org/10.1007/0-387-25822-1_7

  5. Stansfeld S, Gallacher J, Babisch W, Shipley M (1996) Road traffic noise and psychiatric disorder: prospective findings from the Caerphilly Study. BMJ 313(7052):266–267

    Article  CAS  Google Scholar 

  6. Stansfeld SA, Matheson MP (2003) Noise pollution: non-auditory effects on health. Br Med Bull 68:243–257

    Article  Google Scholar 

  7. Stasiewicz PR, Lisman SA (1989) Effects of infant cries on alcohol consumption in college males at risk for child abuse. Child Abuse Negl 13(4):463–470

    Article  CAS  Google Scholar 

  8. Koob GF (2015) The dark side of emotion: the addiction perspective. Eur J Pharmacol 753:73–87. https://doi.org/10.1016/j.ejphar.2014.11.044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Barker DJ, Bercovicz D, Servilio LC, Simmons SJ, Ma S, Root DH, Pawlak AP, West MO (2014) Rat ultrasonic vocalizations demonstrate that the motivation to contextually reinstate cocaine-seeking behavior does not necessarily involve a hedonic response. Addict Biol 19(5):781–790. https://doi.org/10.1111/adb.12044

    Article  PubMed  Google Scholar 

  10. Heilig M, Egli M, Crabbe JC, Becker HC (2010) Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked? Addict Biol 15(2):169–184. https://doi.org/10.1111/j.1369-1600.2009.00194.x

    Article  PubMed  PubMed Central  Google Scholar 

  11. El Hage C, Rappeneau V, Etievant A, Morel AL, Scarna H, Zimmer L, Berod A (2012) Enhanced anxiety observed in cocaine withdrawn rats is associated with altered reactivity of the dorsomedial prefrontal cortex. PLoS One 7(8):e43535. https://doi.org/10.1371/journal.pone.0043535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Markou A, Koob GF (1991) Postcocaine anhedonia. An animal model of cocaine withdrawal. Neuropsychopharmacology 4(1):17–26

    CAS  PubMed  Google Scholar 

  13. Sinha R, Fox HC, Hong KA, Bergquist K, Bhagwagar Z, Siedlarz KM (2009) Enhanced negative emotion and alcohol craving, and altered physiological responses following stress and cue exposure in alcohol dependent individuals. Neuropsychopharmacology 34(5):1198–1208. https://doi.org/10.1038/npp.2008.78

    Article  CAS  PubMed  Google Scholar 

  14. Galea S, Nandi A, Vlahov D (2004) The social epidemiology of substance use. Epidemiol Rev 26:36–52

    Article  Google Scholar 

  15. Knipschild P, Oudshoorn N (1977) VII. Medical effects of aircraft noise: drug survey. Int Arch Occup Environ Health 40(3):197–200

    Article  CAS  Google Scholar 

  16. Kupferschmidt DA, Brown ZJ, Erb S (2011) A procedure for studying the footshock-induced reinstatement of cocaine seeking in laboratory rats. J Vis Exp (47). doi:https://doi.org/10.3791/2265

  17. Gilpin NW, Herman MA, Roberto M (2015) The central amygdala as an integrative hub for anxiety and alcohol use disorders. Biol Psychiatry 77(10):859–869. https://doi.org/10.1016/j.biopsych.2014.09.008

    Article  PubMed  Google Scholar 

  18. Venniro M, Caprioli D, Zhang M, Whitaker LR, Zhang S, Warren BL, Cifani C, Marchant NJ et al (2017) The anterior insular cortex→ central amygdala glutamatergic pathway is critical to relapse after contingency management. Neuron 96(2):414–427.e418

    Article  CAS  Google Scholar 

  19. Goosens KA, Maren S (2001) Contextual and auditory fear conditioning are mediated by the lateral, basal, and central amygdaloid nuclei in rats. Learn Mem 8(3):148–155

    Article  CAS  Google Scholar 

  20. Manohar S, Spoth J, Radziwon K, Auerbach BD, Salvi R (2017) Noise-induced hearing loss induces loudness intolerance in a rat Active Sound Avoidance Paradigm (ASAP). Hear Res 353:197–203. https://doi.org/10.1016/j.heares.2017.07.001

    Article  PubMed  PubMed Central  Google Scholar 

  21. Valdez GR, Sabino V, Koob GF (2004) Increased anxiety-like behavior and ethanol self-administration in dependent rats: reversal via corticotropin-releasing factor-2 receptor activation. Alcohol Clin Exp Res 28(6):865–872

    Article  CAS  Google Scholar 

  22. Kim NJ, Ryu Y, Lee BH, Chang S, Fan Y, Gwak YS, Yang CH, Bills KB, Steffensen SC, Koo JS (2018) Acupuncture inhibition of methamphetamine-induced behaviors, dopamine release and hyperthermia in the nucleus accumbens: mediation of group II mGluR. Addict Biol 24(2):206–217

    Article  Google Scholar 

  23. Kim DH, Ryu YH, Hahm DH, Sohn BY, Shim I, Kwon OS, Chang S, Gwak YS, Kim MS, Kim JH, Lee BH, Jang EY, Zhao RJ, Chung JM, Yang CH, Kim HY (2017) Acupuncture points can be identified as cutaneous neurogenic inflammatory spots. Sci Rep in press. doi:https://doi.org/10.1038/s41598-017-14359-z

  24. Jin W, Kim MS, Jang EY, Lee JY, Lee JG, Kim HY, Yoon SS, Lee BH et al (2018) Acupuncture reduces relapse to cocaine-seeking behavior via activation of GABA neurons in the ventral tegmental area. Addict Biol 23(1):165–181. https://doi.org/10.1111/adb.12499

    Article  CAS  PubMed  Google Scholar 

  25. Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates in stereotaxic coordinates, 6th edn. Academic Press, San Diego

    Google Scholar 

  26. Pang YY, Chen XY, Xue Y, Han XH, Chen L (2015) Effects of secretin on neuronal activity and feeding behavior in central amygdala of rats. Peptides 66:1–8. https://doi.org/10.1016/j.peptides.2015.01.012

    Article  CAS  PubMed  Google Scholar 

  27. Chang S, Ryu Y, Gwak YS, Kim NJ, Kim JM, Lee JY, Kim SA, Lee BH et al (2017) Spinal pathways involved in somatosensory inhibition of the psychomotor actions of cocaine. Sci Rep 7(1):5359. https://doi.org/10.1038/s41598-017-05681-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Jang EY, Ryu YH, Lee BH, Chang SC, Yeo MJ, Kim SH, Folsom RJ, Schilaty ND et al (2015) Involvement of reactive oxygen species in cocaine-taking behaviors in rats. Addict Biol 20(4):663–675. https://doi.org/10.1111/adb.12159

    Article  CAS  PubMed  Google Scholar 

  29. Marek R, Strobel C, Bredy TW, Sah P (2013) The amygdala and medial prefrontal cortex: partners in the fear circuit. J Physiol 591(10):2381–2391

    Article  CAS  Google Scholar 

  30. Borta A, Wohr M, Schwarting RK (2006) Rat ultrasonic vocalization in aversively motivated situations and the role of individual differences in anxiety-related behavior. Behav Brain Res 166(2):271–280. https://doi.org/10.1016/j.bbr.2005.08.009

    Article  CAS  PubMed  Google Scholar 

  31. Brudzynski SM (2013) Ethotransmission: communication of emotional states through ultrasonic vocalization in rats. Curr Opin Neurobiol 23(3):310–317. https://doi.org/10.1016/j.conb.2013.01.014

    Article  CAS  PubMed  Google Scholar 

  32. Kim EJ, Kim ES, Covey E, Kim JJ (2010) Social transmission of fear in rats: the role of 22-kHz ultrasonic distress vocalization. PLoS One 5(12):e15077. https://doi.org/10.1371/journal.pone.0015077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wöhr M, Schwarting RK (2007) Ultrasonic communication in rats: can playback of 50-kHz calls induce approach behavior? PLoS One 2(12):e1365

    Article  Google Scholar 

  34. Noble RE (2002) Diagnosis of stress. Metab Clin Exp 51(6 Suppl 1):37–39

    Article  CAS  Google Scholar 

  35. Aseltine RH Jr, Gore S, Gordon J (2000) Life stress, anger and anxiety, and delinquency: an empirical test of general strain theory. J Health Soc Behav 41(3):256–275

    Article  Google Scholar 

  36. Fiedler N, Laumbach R, Kelly-McNeil K, Lioy P, Fan ZH, Zhang J, Ottenweller J, Ohman-Strickland P et al (2005) Health effects of a mixture of indoor air volatile organics, their ozone oxidation products, and stress. Environ Health Perspect 113(11):1542–1548

    Article  CAS  Google Scholar 

  37. Lee PS, Sohn JN, Lee YM, Park EY, Park JS (2005) A correlational study among perceived stress, anger expression, and depression in cancer patients. Taehan Kanho Hakhoe Chi 35(1):195–205

    CAS  PubMed  Google Scholar 

  38. Daniels W, Richter L, Stein D (2004) The effects of repeated intra-amygdala CRF injections on rat behavior and HPA axis function after stress. Metab Brain Dis 19(1–2):15–23

    Article  CAS  Google Scholar 

  39. Bressan RA, Crippa JA (2005) The role of dopamine in reward and pleasure behaviour--review of data from preclinical research. Acta Psychiatr Scand Suppl 111(427):14–21. https://doi.org/10.1111/j.1600-0447.2005.00540.x

    Article  Google Scholar 

  40. Albein-Urios N, Verdejo-Roman J, Asensio S, Soriano-Mas C, Martinez-Gonzalez JM, Verdejo-Garcia A (2014) Re-appraisal of negative emotions in cocaine dependence: dysfunctional corticolimbic activation and connectivity. Addict Biol 19(3):415–426. https://doi.org/10.1111/j.1369-1600.2012.00497.x

    Article  PubMed  Google Scholar 

  41. Witkiewitz K, Villarroel NA (2009) Dynamic association between negative affect and alcohol lapses following alcohol treatment. J Consult Clin Psychol 77(4):633–644. https://doi.org/10.1037/a0015647

    Article  PubMed  PubMed Central  Google Scholar 

  42. Shiffman S, Waters AJ (2004) Negative affect and smoking lapses: a prospective analysis. J Consult Clin Psychol 72(2):192–201. https://doi.org/10.1037/0022-006X.72.2.192

    Article  PubMed  Google Scholar 

  43. Logrip ML, Zorrilla EP, Koob GF (2012) Stress modulation of drug self-administration: implications for addiction comorbidity with post-traumatic stress disorder. Neuropharmacology 62(2):552–564. https://doi.org/10.1016/j.neuropharm.2011.07.007

    Article  CAS  PubMed  Google Scholar 

  44. Erb S, Shaham Y, Stewart J (1996) Stress reinstates cocaine-seeking behavior after prolonged extinction and a drug-free period. Psychopharmacology 128(4):408–412

    Article  CAS  Google Scholar 

  45. Shaham Y, Stewart J (1995) Stress reinstates heroin-seeking in drug-free animals: an effect mimicking heroin, not withdrawal. Psychopharmacology 119(3):334–341

    Article  CAS  Google Scholar 

  46. LeDoux JE (2014) Coming to terms with fear. Proc Natl Acad Sci U S A 111(8):2871–2878. https://doi.org/10.1073/pnas.1400335111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Mahan AL, Ressler KJ (2012) Fear conditioning, synaptic plasticity and the amygdala: implications for posttraumatic stress disorder. Trends Neurosci 35(1):24–35. https://doi.org/10.1016/j.tins.2011.06.007

    Article  CAS  PubMed  Google Scholar 

  48. Warlow SM, Robinson MJF, Berridge KC (2017) Optogenetic central amygdala stimulation intensifies and narrows motivation for cocaine. J Neurosci 37(35):8330–8348. https://doi.org/10.1523/JNEUROSCI.3141-16.2017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ahn S, Phillips AG (2002) Modulation by central and basolateral amygdalar nuclei of dopaminergic correlates of feeding to satiety in the rat nucleus accumbens and medial prefrontal cortex. J Neurosci 22(24):10958–10965

    Article  CAS  Google Scholar 

  50. Grimsley JM, Hazlett EG, Wenstrup JJ (2013) Coding the meaning of sounds: contextual modulation of auditory responses in the basolateral amygdala. J Neurosci 33(44):17538–17548. https://doi.org/10.1523/JNEUROSCI.2205-13.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Phelps EA, LeDoux JE (2005) Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron 48(2):175–187. https://doi.org/10.1016/j.neuron.2005.09.025

    Article  CAS  PubMed  Google Scholar 

  52. Wassum KM, Izquierdo A (2015) The basolateral amygdala in reward learning and addiction. Neurosci Biobehav Rev 57:271–283. https://doi.org/10.1016/j.neubiorev.2015.08.017

    Article  PubMed  PubMed Central  Google Scholar 

  53. McCutcheon JE, Ebner SR, Loriaux AL, Roitman MF (2012) Encoding of aversion by dopamine and the nucleus accumbens. Front Neurosci 6:137. https://doi.org/10.3389/fnins.2012.00137

    Article  PubMed  PubMed Central  Google Scholar 

  54. Twining RC, Wheeler DS, Ebben AL, Jacobsen AJ, Robble MA, Mantsch JR, Wheeler RA (2015) Aversive stimuli drive drug seeking in a state of low dopamine tone. Biol Psychiatry 77(10):895–902. https://doi.org/10.1016/j.biopsych.2014.09.004

    Article  CAS  PubMed  Google Scholar 

  55. Ungless MA, Magill PJ, Bolam JP (2004) Uniform inhibition of dopamine neurons in the ventral tegmental area by aversive stimuli. Science 303(5666):2040–2042. https://doi.org/10.1126/science.1093360

    Article  CAS  PubMed  Google Scholar 

  56. Everitt BJ, Cardinal RN, Hall J, Parkinson J, Robbins T (2000) Chapter 10: differential involvement of amygdala subsystems in appetitive conditioning and drug addiction. In: Aggleton JP (ed) The amygdala: a functional analysis, 2nd edn. Oxford University Press, New York, pp 353–390

    Google Scholar 

  57. Howland JG, Taepavarapruk P, Phillips AG (2002) Glutamate receptor-dependent modulation of dopamine efflux in the nucleus accumbens by basolateral, but not central, nucleus of the amygdala in rats. J Neurosci 22(3):1137–1145

    Article  CAS  Google Scholar 

  58. Wang GJ, Smith L, Volkow ND, Telang F, Logan J, Tomasi D, Wong CT, Hoffman W et al (2012) Decreased dopamine activity predicts relapse in methamphetamine abusers. Mol Psychiatry 17(9):918–925. https://doi.org/10.1038/mp.2011.86

    Article  CAS  PubMed  Google Scholar 

  59. Tsibulsky VL, Norman AB (1999) Satiety threshold: a quantitative model of maintained cocaine self-administration. Brain Res 839(1):85–93

    Article  CAS  Google Scholar 

  60. Wise RA, Newton P, Leeb K, Burnette B, Pocock D, Justice JB Jr (1995) Fluctuations in nucleus accumbens dopamine concentration during intravenous cocaine self-administration in rats. Psychopharmacology 120(1):10–20

    Article  CAS  Google Scholar 

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Acknowledgements

General: SC and HYK designed the experiment. SC, YF, JHS, YR, SCS, HKK, JMK, MSK, BHL, and EYJ performed the experiments and analyzed the data. SC, CHY, and HYK drafted the manuscript. HYK was responsible for the overall direction of the project and for the edits to the manuscript.

Funding

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2018R1A5A2025272, 2018R1E1A2A02086499, and 2018R1A6A3A01013294), the KBRI basic research program through the Korea Brain Research Institute funded by the Ministry of Science and ICT (19-BR-03-01), and the Korea Institute of Oriental Medicine (KIOM) (KSN1812181).

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  1. Suchan Chang and Yu Fan contributed equally to this work.

Authors and Affiliations

  1. Department of Physiology, College of Korean Medicine, Daegu Haany University, Daegu, 42158, South Korea

    Suchan Chang, Yu Fan, Joo Hyun Shin, Mi Seon Kim, Hyung Kyu Kim, Jin Mook Kim, Bong Hyo Lee, Eun Young Jang, Chae Ha Yang & Hee Young Kim

  2. Korean Medicine Fundamental Research Division, Korea Institute of Oriental Medicine, Daejeon, 34054, South Korea

    Yeonhee Ryu

  3. Department of Psychology and Neuroscience (1050 SWKT), Brigham Young University, Provo, UT, 84602, USA

    Scott C. Steffensen

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  1. Suchan Chang
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Chang, S., Fan, Y., Shin, J.H. et al. Unpleasant Sound Elicits Negative Emotion and Reinstates Drug Seeking. Mol Neurobiol 56, 7594–7607 (2019). https://doi.org/10.1007/s12035-019-1609-z

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