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Social odor choice buffers drug craving

Neuropsychopharmacology volume 49, pages 731–739 (2024)Cite this article

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Abstract

Social interactions are rewarding and protective against substance use disorders, but it is unclear which specific aspect of the complex sensory social experience drives these effects. Here, we investigated the role of olfactory sensory experience on social interaction, social preference over cocaine, and cocaine craving in rats. First, we conducted bulbectomy on both male and female rats to evaluate the necessity of olfactory system experience on the acquisition and maintenance of volitional social interaction. Next, we assessed the effect of bulbectomy on rats given a choice between social interaction and cocaine. Finally, we evaluated the influence of olfactory sensory experience by training rats on volitional partner-associated odors, assessing their preference for partner odors over cocaine to achieve voluntary abstinence and assessing its effect on the incubation of cocaine craving. Bulbectomy impaired operant social interaction without affecting food and cocaine self-administration. Rats with intact olfactory systems preferred social interaction over cocaine, while rats with impaired olfactory sense showed a preference for cocaine. Providing access to a partner odor in a choice procedure led to cocaine abstinence, preventing incubation of cocaine craving, in contrast to forced abstinence or non-contingent exposure to cocaine and partner odors. Our data suggests the olfactory sensory experience is necessary and sufficient for volitional social reward. Furthermore, the active preference for partner odors over cocaine buffers drug craving. Based on these findings, translational research should explore the use of social sensory-based treatments utilizing odor-focused foundations for individuals with substance use disorders.

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Fig. 1: Olfactory sensory system is critical for acquisition of volitional social interaction.
Fig. 2: Olfactory sensory system is critical for maintenance of volitional social interaction.
Fig. 3: Olfactory sensory system is critical for social preference.
Fig. 4: Social odors mediate volitional social reward.
Fig. 5: Active odor preference prevents incubation of cocaine craving.

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References

  1. Galef BG. Animal communication: sniffing is about more than just smell. Curr Biol. 2013;23:272–73.

    Article  Google Scholar 

  2. Diamond ME, Arabzadeh E. Whisker sensory system - from receptor to decision. Prog Neurobiol. 2013;103:28–40.

    Article  PubMed  Google Scholar 

  3. Ravreby I, Snitz K, Sobel N. There is chemistry in social chemistry. Sci Adv. 2022;8:eabn0154.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Gaby JM, Zayas V. Smelling is telling: human olfactory cues influence social judgments in semi-realistic interactions. Chem Senses. 2017;42:405–18.

    Article  PubMed  Google Scholar 

  5. Boesveldt S, Parma V. The importance of the olfactory system in human well-being, through nutrition and social behavior. Cell Tissue Res. 2021;383:559–67.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Sela L, Sobel N. Human olfaction: a constant state of change-blindness. Exp Brain Res. 2010;205:13–29.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Zelano C, Sobel N. Humans as an animal model for systems-level organization of olfaction. Neuron. 2005;48:431–54.

    Article  CAS  PubMed  Google Scholar 

  8. Roberts SC, Havlicek J, Schaal B. Human olfactory communication: current challenges and future prospects. Philos Trans R Soc Lond B Biol Sci. 2020;375:20190258.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Popik P, Vetulani J, Bisaga A, van Ree JM. Recognition cue in the rat’s social memory paradigm. J Basic Clin Physiol Pharm. 1991;2:315–27.

    Article  CAS  Google Scholar 

  10. Pena RR, Medeiros DC, Guarnieri LO, Guerra JB, Carvalho VR, Mendes E, et al. Home-cage odors spatial cues elicit theta phase/gamma amplitude coupling between olfactory bulb and dorsal hippocampus. Neuroscience. 2017;363:97–106.

    Article  CAS  PubMed  Google Scholar 

  11. Contestabile A, Casarotto G, Girard B, Tzanoulinou S, Bellone C. Deconstructing the contribution of sensory cues in social approach. Eur J Neurosci. 2021;53:3199–211.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gerber N, Schweinfurth MK, Taborsky M. The smell of cooperation: rats increase helpful behaviour when receiving odour cues of a conspecific performing a cooperative task. Proc Biol Sci. 2020;287:20202327.

    PubMed  PubMed Central  Google Scholar 

  13. Lin DY, Zhang SZ, Block E, Katz LC. Encoding social signals in the mouse main olfactory bulb. Nature. 2005;434:470–7.

    Article  CAS  PubMed  ADS  Google Scholar 

  14. Herz RS. Odor-associative learning and emotion: effects on perception and behavior. Chem Senses. 2005;30:i250–1.

    Article  PubMed  Google Scholar 

  15. Prakash N, Matos HY, Sebaoui S, Tsai L, Tran T, Aromolaran A, et al. Connectivity and molecular profiles of Foxp2- and Dbx1-lineage neurons in the accessory olfactory bulb and medial amygdala. J Comp Neurol. 2023.

  16. Herz RS. A naturalistic analysis of autobiographical memories triggered by olfactory visual and auditory stimuli. Chem Senses. 2004;29:217–24. https://doi.org/10.1002/cne.25545.

    Article  PubMed  Google Scholar 

  17. Leschak CJ, Eisenberger NI. The role of social relationships in the link between olfactory dysfunction and mortality. PLoS One. 2018;13:e0196708.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Moberg PJ, Agrin R, Gur RE, Gur RC, Turetsky BI, Doty RL. Olfactory dysfunction in schizophrenia: a qualitative and quantitative review. Neuropsychopharmacology. 1999;21:325–40.

    Article  CAS  PubMed  Google Scholar 

  19. Guay S, Nachar N, Lavoie ME, Marchand A, O’Connor KP. The buffering power of overt socially supportive and unsupportive behaviors from the significant other on posttraumatic stress disorder individuals’ emotional state. Anxiety Stress Coping. 2017;30:52–65.

    Article  PubMed  Google Scholar 

  20. Hamaideh S, Al-Magaireh D, Abu-Farsakh B, Al-Omari H. Quality of life, social support, and severity of psychiatric symptoms in Jordanian patients with schizophrenia. J Psychiatr Ment Health Nurs. 2014;21:455–65.

    Article  CAS  PubMed  Google Scholar 

  21. Mahmut M, Stevenson R. Olfactory abilities and psychopathy: higher psychopathy scores are associated with poorer odor discrimination and identification. Chem Percept. 2012;5:300–07.

    Article  Google Scholar 

  22. Mishor E, Amir D, Weiss T, Honigstein D, Weissbrod A, Livne E, et al. Sniffing the human body volatile hexadecanal blocks aggression in men but triggers aggression in women. Sci Adv. 2021;7:eabg1530.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  23. Squires S, Chichester C, Cirelli D, Divadio L, Hulcher S. Sensory alterations in alcohol abuse. Top Clin Nurs. 1985;6:51–63.

    CAS  PubMed  Google Scholar 

  24. Schafer L, Schriever VA, Croy I. Human olfactory dysfunction: causes and consequences. Cell Tissue Res. 2021;383:569–79.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Papazian EJ, Pinto JM. Olfactory loss and aging: connections with health and well-being. Chem Senses. 2021;46:bjab045.

    Article  PubMed  Google Scholar 

  26. Agarwal K, Luk JW, Manza P, McDuffie C, To L, Jaime-Lara RB, et al. Chemosensory alterations and impact on quality of life in persistent alcohol drinkers. Alcohol Alcohol. 2023;58:84–92.

    Article  PubMed  Google Scholar 

  27. Sayette MA, Marchetti MA, Herz RS, Martin LM, Bowdring MA. Pleasant olfactory cues can reduce cigarette craving. J Abnorm Psychol. 2019;128:327–40.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Klein B, Bautze V, Maier AM, Deussing J, Breer H, Strotmann J. Activation of the mouse odorant receptor 37 subsystem coincides with a reduction of novel environment-induced activity within the paraventricular nucleus of the hypothalamus. Eur J Neurosci. 2015;41:793–801.

    Article  PubMed  Google Scholar 

  29. Niu H, Zheng Y, Rizak JD, Fan Y, Huang W, Ma Y, et al. The effects of lesion of the olfactory epithelium on morphine-induced sensitization and conditioned place preference in mice. Behav Brain Res. 2012;233:71–8.

    Article  CAS  PubMed  Google Scholar 

  30. Venniro M, Zhang M, Caprioli D, Hoots JK, Golden SA, Heins C, et al. Volitional social interaction prevents drug addiction in rat models. Nat Neurosci. 2018;21:1520–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Venniro M, Russell TI, Zhang M, Shaham Y. Operant social reward decreases incubation of heroin craving in male and female rats. Biol Psychiatry. 2019;86:848–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Venniro M, Russell TI, Ramsey LA, Richie CT, Lesscher HMB, Giovanetti SM, et al. Abstinence-dependent dissociable central amygdala microcircuits control drug craving. Proc Natl Acad Sci USA. 2020;117:8126–34.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  33. Venniro M, Panlilio LV, Epstein DH, Shaham Y. The protective effect of operant social reward on cocaine self-administration, choice, and relapse is dependent on delay and effort for the social reward. Neuropsychopharmacology. 2021;46:2350–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Venniro M, Shaham Y. An operant social self-administration and choice model in rats. Nat Protoc. 2020;15:1542–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ramsey LA, Holloman FM, Hope BT, Shaham Y, Venniro M. Waving through the window: a model of volitional social interaction in female mice. Biol Psychiatry. 2022;91:988–97.

  36. Ramsey LA, Holloman FM, Lee SS, Venniro M. An operant social self-administration and choice model in mice. Nat Protoc. 2023;18:1669–86.

    Article  CAS  PubMed  Google Scholar 

  37. Ahmed SH. Validation crisis in animal models of drug addiction: beyond non-disordered drug use toward drug addiction. Neurosci Biobehav Rev. 2010;35:172–84.

    Article  CAS  PubMed  Google Scholar 

  38. Lenoir M, Serre F, Cantin L, Ahmed SH. Intense sweetness surpasses cocaine reward. PLoS One. 2007;2:e698.

    Article  PubMed  PubMed Central  ADS  Google Scholar 

  39. Venniro M, Marino RAM, Chow JJ, Caprioli D, Epstein DH, Ramsey LA, et al. The protective effect of social reward on opioid and psychostimulant reward and relapse: behavior, pharmacology, and brain regions. J Neurosci. 2022;42:9298–314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Venniro M, Reverte I, Ramsey LA, Papastrat KM, D’Ottavio G, Milella MS, et al. Factors modulating the incubation of drug and non-drug craving and their clinical implications. Neurosci Biobehav Rev. 2021;131:847–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Fredriksson I, Venniro M, Reiner DJ, Chow JJ, Bossert JM, Shaham Y. Animal models of drug relapse and craving after voluntary abstinence: a review. Pharm Rev. 2021;73:1050–83.

    Article  CAS  PubMed  Google Scholar 

  42. de Waal FBM, Preston SD. Mammalian empathy: behavioural manifestations and neural basis. Nat Rev Neurosci. 2017;18:498–509.

    Article  PubMed  Google Scholar 

  43. Chadman KK, Yang M, Crawley JN. Criteria for validating mouse models of psychiatric diseases. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:1–11.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Venniro M, Banks ML, Heilig M, Epstein DH, Shaham Y. Improving translation of animal models of addiction and relapse by reverse translation. Nat Rev Neurosci. 2020;21:625–43.

    Article  CAS  PubMed  Google Scholar 

  45. Robinson TE, Berridge KC. The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev. 1993;18:247–91.

    Article  CAS  PubMed  Google Scholar 

  46. Edwards DA, Thompson ML, Burge KG. Olfactory bulb removal vs peripherally induced anosmia: differential effects on the aggressive behavior of male mice. Behav Biol. 1972;7:823–8.

    Article  CAS  PubMed  Google Scholar 

  47. Li Q, Takeuchi Y, Wang J, Gellert L, Barcsai L, Pedraza LK, et al. Reinstating olfactory bulb-derived limbic gamma oscillations alleviates depression-like behavioral deficits in rodents. Neuron 2023;111:2065–75.e5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Leinders-Zufall T, Lane AP, Puche AC, Ma W, Novotny MV, Shipley MT, et al. Ultrasensitive pheromone detection by mammalian vomeronasal neurons. Nature. 2000;405:792–6.

    Article  CAS  PubMed  ADS  Google Scholar 

  49. Albrechet-Souza L, Gilpin NW. The predator odor avoidance model of post-traumatic stress disorder in rats. Behav Pharm. 2019;30:105–14.

    Article  Google Scholar 

  50. Verbitsky A, Dopfel D, Zhang N. Rodent models of post-traumatic stress disorder: behavioral assessment. Transl Psychiatry. 2020;10:132.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Caprioli D, Venniro M, Zeric T, Li X, Adhikary S, Madangopal R, et al. Effect of the novel positive allosteric modulator of metabotropic glutamate receptor 2 azd8529 on incubation of methamphetamine craving after prolonged voluntary abstinence in a rat model. Biol Psychiatry. 2015;78:463–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Caprioli D, Venniro M, Zhang M, Bossert JM, Warren BL, Hope BT, et al. Role of dorsomedial striatum neuronal ensembles in incubation of methamphetamine craving after voluntary abstinence. J Neurosci. 2017;37:1014–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Venniro M, Zhang M, Shaham Y, Caprioli D. Incubation of methamphetamine but not heroin craving after voluntary abstinence in male and female rats. Neuropsychopharmacology. 2017;42:1126–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Aklin WM, Wong CJ, Hampton J, Svikis DS, Stitzer ML, Bigelow GE, et al. A therapeutic workplace for the long-term treatment of drug addiction and unemployment: eight-year outcomes of a social business intervention. J Subst Abus Treat. 2014;47:329–38.

    Article  Google Scholar 

  55. Silverman K, DeFulio A, Sigurdsson SO. Maintenance of reinforcement to address the chronic nature of drug addiction. Prev Med. 2012;55:S46–53.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Azrin NH. Improvements in the community-reinforcement approach to alcoholism. Behav Res Ther. 1976;14:339–48.

    Article  CAS  PubMed  Google Scholar 

  57. Stitzer ML, Jones HE, Tuten M, Wong C. Community reinforcement approach and contingency management interventions for substance abuse. In W M Cox, E Klinger, editors. Handbook of Motivational Counseling: Goal-Based Approaches to Assessment and Intervention with Addiction and Other Problems. Chichester, UK: John Wiley & Sons, Ltd; 2011.

  58. Lash SJ, Burden JL, Monteleone BR, Lehmann LP. Social reinforcement of substance abuse treatment aftercare participation: Impact on outcome. Addict Behav. 2004;29:337–42.

    Article  PubMed  Google Scholar 

  59. Masuo Y, Satou T, Takemoto H, Koike K. Smell and stress response in the brain: review of the connection between chemistry and neuropharmacology. Molecules. 2021;26:2571.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Spence C. The scent of attraction and the smell of success: crossmodal influences on person perception. Cogn Res Princ Implic. 2021;6:46.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Roberts RO, Christianson TJ, Kremers WK, Mielke MM, Machulda MM, Vassilaki M, et al. Association between olfactory dysfunction and amnestic mild cognitive impairment and alzheimer disease dementia. JAMA Neurol. 2016;73:93–101.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Wiggins LD, Robins DL, Bakeman R, Adamson LB. Brief report: sensory abnormalities as distinguishing symptoms of autism spectrum disorders in young children. J Autism Dev Disord. 2009;39:1087–91.

    Article  PubMed  Google Scholar 

  63. Rupp CI, Kurz M, Kemmler G, Mair D, Hausmann A, Hinterhuber H, et al. Reduced olfactory sensitivity, discrimination, and identification in patients with alcohol dependence. Alcohol Clin Exp Res. 2003;27:432–9.

    Article  PubMed  Google Scholar 

  64. Doty RL. Olfactory dysfunction in neurodegenerative diseases: is there a common pathological substrate? Lancet Neurol. 2017;16:478–88.

    Article  PubMed  Google Scholar 

  65. Tonacci A, Bruno RM, Ghiadoni L, Pratali L, Berardi N, Tognoni G, et al. Olfactory evaluation in Mild Cognitive Impairment: correlation with neurocognitive performance and endothelial function. Eur J Neurosci. 2017;45:1279–88.

    Article  PubMed  Google Scholar 

  66. Hollander E, Bartz J, Chaplin W, Phillips A, Sumner J, Soorya L, et al. Oxytocin increases retention of social cognition in autism. Biol Psychiatry. 2007;61:498–503.

    Article  CAS  PubMed  Google Scholar 

  67. Slotnick B. Animal cognition and the rat olfactory system. Trends Cogn Sci. 2001;5:216–22.

    Article  CAS  PubMed  Google Scholar 

  68. Munger SD, Leinders-Zufall T, McDougall LM, Cockerham RE, Schmid A, Wandernoth P, et al. An olfactory subsystem that detects carbon disulfide and mediates food-related social learning. Curr Biol. 2010;20:1438–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Dr. Yavin Shaham for input and support during the manuscript preparation.

Funding

The research was supported by a grant from NIDCD [DC010915] (ACP), a grant from NIDA [DA047976] (MV) and BBRF Young Investigator Grant [28897] (MV).

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Authors and Affiliations

  1. Department of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA

    Kimberly M. Papastrat, Cody A. Lis, Hanna Pickard, Adam C. Puche & Marco Venniro

  2. Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA

    Kimberly M. Papastrat, Cody A. Lis, Adam C. Puche & Marco Venniro

  3. Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy

    Daniele Caprioli

  4. Santa Lucia Foundation (IRCCS Fondazione Santa Lucia), Rome, Italy

    Daniele Caprioli

  5. Department of Philosophy & Berman Institute of Bioethics, Johns Hopkins University, Baltimore, MD, USA

    Hanna Pickard

  6. Intramural Research Program, NIDA, NIH, Baltimore, MD, USA

    Leslie A. Ramsey

  7. Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA

    Marco Venniro

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  1. Kimberly M. Papastrat
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Contributions

KMP, ACP, and MV conceptualized the project; KMP, CAL, and MV designed the experiments and collected the behavioral data; KMP, and MV analyzed the data; KMP, CAL, DC, HP, ACP, LAR, and MV contributed to different aspects of the write-up of the paper.

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Correspondence to Marco Venniro.

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Papastrat, K.M., Lis, C.A., Caprioli, D. et al. Social odor choice buffers drug craving. Neuropsychopharmacol. 49, 731–739 (2024). https://doi.org/10.1038/s41386-023-01778-y

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