Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Oxytocin attenuates the retrieval of methamphetamine-associated reward memories by enhancing adult hippocampal neurogenesis in mice

Molecular Psychiatry volume 30, pages 5664–5679 (2025)Cite this article

Subjects

Abstract

The present study was designated to investigate the effect of oxytocin (OXT) on the retrieval of methamphetamine (METH)-associated reward memories induced by drugs in mice and its underlying mechanisms related to adult hippocampal neurogenesis (AHN) and memory engrams. The data showed that repeated hippocampal microinjections of OXT (1.25 and 2.5 μg) for 8 consecutive days significantly prevented the retrieval of METH-associated reward memories induced by drugs in a time-, dose- and receptor-dependent manner in mice. At the meanwhile, OXT was found to markedly elevate AHN levels, enhancing the proliferation, survival and maturation of newborn neurons by using NestinCreERT2::Rosa26-tdTomato mice and BrdU labeling. Notably, reduction or depletion of AHN by temozolomide (TMZ) or NestinCreERT2 mice combined with adeno-associated viruses (AAVs) (AAV-CAG-DIO-rtTA-EGFP and AAV-TRE-DTA) could attenuate the inhibition of OXT on the retrieval of METH-associated reward memories in mice. By using activity-dependent labeling strategy in mice, it was observed that the retrieval of METH-associated reward memories was mediated by activation of METH-associated memory engrams in the dentate gyrus (DG) region of the hippocampus. Repeated hippocampal microinjections of OXT effectively prevented the activation of these memory engrams, which could be abolished after reducing AHN by TMZ. In summary, this study revealed that OXT effectively prevented the retrieval of METH-associated reward memories induced by drugs in mice, which may be related to its enhancement on AHN as well as inhibition on METH-associated memory engrams in DG.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: OXT prevented the retrieval of METH-associated reward memories induced by drugs in mice.
Fig. 2: OXT enhanced DCX+ cells expression in METH-treated mice.
Fig. 3: OXT prevented the retrieval of METH-associated reward memories induced by drugs through enhancing AHN in mice.
Fig. 4: OXT promoted the proliferation of newborn neurons in DG of METH-treated mice.
Fig. 5: OXT enhanced the survival and maturation of newborn neurons in DG of METH-treated mice.
Fig. 6: OXT suppressed the reactivation of METH-associated memory engrams within DG of mice in related to enhancing AHN.

Similar content being viewed by others

Data availability

All data needed for the conclusion in the present study were presented in the manuscript and Supplementary Materials. Additional data to this paper may be requested from the corresponding authors.

References

  1. Morley KC, Cornish JL, Faingold A, Wood K, Haber PS. Pharmacotherapeutic agents in the treatment of methamphetamine dependence. Expert Opin Investig Drugs. 2017;26:563–78.

    PubMed  CAS  Google Scholar 

  2. Bauml KT, Trissl L. Selective memory retrieval can revive forgotten memories. Proc Natl Acad Sci USA. 2022;119:e2114377119.

    PubMed  PubMed Central  Google Scholar 

  3. Keyes PC, Adams EL, Chen Z, Bi L, Nachtrab G, Wang VJ, et al. Orchestrating opiate-associated memories in thalamic circuits. Neuron. 2020;107:1113–23 e1114.

    PubMed  PubMed Central  CAS  Google Scholar 

  4. Tsai ST, Liew HK, Li HM, Lin SZ, Chen SY. Harnessing neurogenesis and neuroplasticity with stem cell treatment for addictive disorders. Cell Transpl. 2019;28:1127–31.

    Google Scholar 

  5. Che X, Bai Y, Cai J, Liu Y, Li Y, Yin M, et al. Hippocampal neurogenesis interferes with extinction and reinstatement of methamphetamine-associated reward memory in mice. Neuropharmacology. 2021;196:108717.

    PubMed  CAS  Google Scholar 

  6. Toni N, Schinder AF. Maturation and functional integration of new granule cells into the adult hippocampus. Cold Spring Harb Perspect Biol. 2015;8:a018903.

    PubMed  Google Scholar 

  7. Toni N, Teng EM, Bushong EA, Aimone JB, Zhao C, Consiglio A, et al. Synapse formation on neurons born in the adult hippocampus. Nat Neurosci. 2007;10:727–34.

    PubMed  CAS  Google Scholar 

  8. Toni N, Laplagne DA, Zhao C, Lombardi G, Ribak CE, Gage FH, et al. Neurons born in the adult dentate gyrus form functional synapses with target cells. Nat Neurosci. 2008;11:901–7.

    PubMed  PubMed Central  CAS  Google Scholar 

  9. Josselyn SA, Tonegawa S. Memory engrams: recalling the past and imagining the future. Science. 2020;367:eaaw4325.

    PubMed  PubMed Central  CAS  Google Scholar 

  10. Akers KG, Martinez-Canabal A, Restivo L, Yiu AP, De Cristofaro A, Hsiang HL, et al. Hippocampal neurogenesis regulates forgetting during adulthood and infancy. Science. 2014;344:598–602.

    PubMed  CAS  Google Scholar 

  11. Roy DS, Muralidhar S, Smith LM, Tonegawa S. Silent memory engrams as the basis for retrograde amnesia. Proc Natl Acad Sci USA. 2017;114:E9972–E9979.

    PubMed  PubMed Central  CAS  Google Scholar 

  12. Wang C, Yue H, Hu Z, Shen Y, Ma J, Li J, et al. Microglia mediate forgetting via complement-dependent synaptic elimination. Science. 2020;367:688–94.

    PubMed  CAS  Google Scholar 

  13. Ko SY, Frankland PW. Neurogenesis-dependent transformation of hippocampal engrams. Neurosci Lett. 2021;762:136176.

    PubMed  CAS  Google Scholar 

  14. Guskjolen A, Kenney JW, de la Parra J, Yeung BA, Josselyn SA, Frankland PW. Recovery of “Lost” infant memories in mice. Curr Biol. 2018;28:2283–90.e2283.

    PubMed  CAS  Google Scholar 

  15. Lopez-Oropeza G, Duran P, Martinez-Canabal A. Maternal enrichment increases infantile spatial amnesia mediated by postnatal neurogenesis modulation. Front Behav Neurosci. 2022;16:971359.

    PubMed  PubMed Central  CAS  Google Scholar 

  16. Vasudevan K, Hassell JE Jr, Maren S. Hippocampal engrams and contextual memory. Adv Neurobiol. 2024;38:45–66.

    PubMed  PubMed Central  Google Scholar 

  17. Zhou Y, Zhu H, Liu Z, Chen X, Su X, Ma C, et al. A ventral CA1 to nucleus accumbens core engram circuit mediates conditioned place preference for cocaine. Nat Neurosci. 2019;22:1986–99.

    PubMed  CAS  Google Scholar 

  18. Trouche S, Perestenko PV, van de Ven GM, Bratley CT, McNamara CG, Campo-Urriza N, et al. Recoding a cocaine-place memory engram to a neutral engram in the hippocampus. Nat Neurosci. 2016;19:564–7.

    PubMed  PubMed Central  CAS  Google Scholar 

  19. Qi S, Tan SM, Wang R, Higginbotham JA, Ritchie JL, Ibarra CK, et al. Optogenetic inhibition of the dorsal hippocampus CA3 region during early-stage cocaine-memory reconsolidation disrupts subsequent context-induced cocaine seeking in rats. Neuropsychopharmacology. 2022;47:1473–83.

    PubMed  PubMed Central  CAS  Google Scholar 

  20. Xia L, Nygard SK, Sobczak GG, Hourguettes NJ, Bruchas MR. Dorsal-CA1 hippocampal neuronal ensembles encode nicotine-reward contextual associations. Cell Rep. 2017;19:2143–56.

    PubMed  PubMed Central  CAS  Google Scholar 

  21. Dai Z, Liu Y, Nie L, Chen W, Xu X, Li Y, et al. Locus coeruleus input-modulated reactivation of dentate gyrus opioid-withdrawal engrams promotes extinction. Neuropsychopharmacology. 2023;48:327–40.

    PubMed  CAS  Google Scholar 

  22. Cincotta C, Ruesch E, Senne R, Ramirez S. Hippocampal fear engrams modulate ethanol-induced maladaptive contextual generalization in mice. Hippocampus. 2022;32:707–15.

    PubMed  PubMed Central  CAS  Google Scholar 

  23. Sharma SR, Gonda X, Dome P, Tarazi FI. What’s love got to do with it: role of oxytocin in trauma, attachment and resilience. Pharmacol Ther. 2020;214:107602.

    PubMed  CAS  Google Scholar 

  24. Gulliver D, Werry E, Reekie TA, Katte TA, Jorgensen W, Kassiou M. Targeting the oxytocin system: new pharmacotherapeutic approaches. Trends Pharmacol Sci. 2019;40:22–37.

    PubMed  CAS  Google Scholar 

  25. Yoon S, Kim YK. The Role of the oxytocin system in anxiety disorders. Adv Exp Med Biol. 2020;1191:103–20.

    PubMed  CAS  Google Scholar 

  26. Georgiou P, Zanos P, Garcia-Carmona JA, Hourani S, Kitchen I, Laorden ML, et al. Methamphetamine abstinence induces changes in mu-opioid receptor, oxytocin and CRF systems: association with an anxiogenic phenotype. Neuropharmacology. 2016;105:520–32.

    PubMed  CAS  Google Scholar 

  27. Zanos P, Wright SR, Georgiou P, Yoo JH, Ledent C, Hourani SM, et al. Chronic methamphetamine treatment induces oxytocin receptor up-regulation in the amygdala and hypothalamus via an adenosine A2A receptor-independent mechanism. Pharmacol Biochem Behav. 2014;119:72–79.

    PubMed  CAS  Google Scholar 

  28. Everett N, Baracz S, Cornish J. Oxytocin treatment in the prelimbic cortex reduces relapse to methamphetamine-seeking and is associated with reduced activity in the rostral nucleus accumbens core. Pharmacol Biochem Behav. 2019;183:64–71.

    PubMed  CAS  Google Scholar 

  29. Everett NA, McGregor IS, Baracz SJ, Cornish JL. The role of the vasopressin V1A receptor in oxytocin modulation of methamphetamine primed reinstatement. Neuropharmacology. 2018;133:1–11.

    PubMed  CAS  Google Scholar 

  30. Everett NA, Baracz SJ, Cornish JL. The effect of chronic oxytocin treatment during abstinence from methamphetamine self-administration on incubation of craving, reinstatement, and anxiety. Neuropsychopharmacology. 2020;45:597–605.

    PubMed  Google Scholar 

  31. Hicks C, Cornish JL, Baracz SJ, Suraev A, McGregor IS. Adolescent pre-treatment with oxytocin protects against adult methamphetamine-seeking behavior in female rats. Addict Biol. 2016;21:304–15.

    PubMed  CAS  Google Scholar 

  32. Cox BM, Bentzley BS, Regen-Tuero H, See RE, Reichel CM, Aston-Jones G. Oxytocin acts in nucleus accumbens to attenuate methamphetamine seeking and demand. Biol Psychiatry. 2017;81:949–58.

    PubMed  CAS  Google Scholar 

  33. Han WY, Du P, Fu SY, Wang F, Song M, Wu CF, et al. Oxytocin via its receptor affects restraint stress-induced methamphetamine CPP reinstatement in mice: Involvement of the medial prefrontal cortex and dorsal hippocampus glutamatergic system. Pharmacol Biochem Behav. 2014;119:80–87.

    PubMed  CAS  Google Scholar 

  34. Baracz SJ, Rourke PI, Pardey MC, Hunt GE, McGregor IS, Cornish JL. Oxytocin directly administered into the nucleus accumbens core or subthalamic nucleus attenuates methamphetamine-induced conditioned place preference. Behav Brain Res. 2012;228:185–93.

    PubMed  CAS  Google Scholar 

  35. Cai J, Che X, Xu T, Luo Y, Yin M, Lu X, et al. Repeated oxytocin treatment during abstinence inhibited context- or restraint stress-induced reinstatement of methamphetamine-conditioned place preference and promoted adult hippocampal neurogenesis in mice. Exp Neurol. 2022;347:113907.

    PubMed  CAS  Google Scholar 

  36. Che X, Cai J, Liu Y, Xu T, Yang J, Wu C. Oxytocin signaling in the treatment of drug addiction: therapeutic opportunities and challenges. Pharmacol Ther. 2021;223:107820.

    PubMed  CAS  Google Scholar 

  37. Fan XY, Yang JY, Dong YX, Hou Y, Liu S, Wu CF. Oxytocin inhibits methamphetamine-associated learning and memory alterations by regulating DNA methylation at the synaptophysin promoter. Addict Biol. 2020;25:e12697.

    PubMed  Google Scholar 

  38. Qi J, Han WY, Yang JY, Wang LH, Dong YX, Wang F, et al. Oxytocin regulates changes of extracellular glutamate and GABA levels induced by methamphetamine in the mouse brain. Addict Biol. 2012;17:758–69.

    PubMed  CAS  Google Scholar 

  39. Yang JY, Qi J, Han WY, Wang F, Wu CF. Inhibitory role of oxytocin in psychostimulant-induced psychological dependence and its effects on dopaminergic and glutaminergic transmission. Acta Pharmacol Sin. 2010;31:1071–4.

    PubMed  PubMed Central  CAS  Google Scholar 

  40. Qi J, Yang JY, Wang F, Zhao YN, Song M, Wu CF. Effects of oxytocin on methamphetamine-induced conditioned place preference and the possible role of glutamatergic neurotransmission in the medial prefrontal cortex of mice in reinstatement. Neuropharmacology. 2009;56:856–65.

    PubMed  CAS  Google Scholar 

  41. Qi J, Yang JY, Song M, Li Y, Wang F, Wu CF. Inhibition by oxytocin of methamphetamine-induced hyperactivity related to dopamine turnover in the mesolimbic region in mice. Naunyn Schmiedebergs Arch Pharmacol. 2008;376:441–8.

    PubMed  CAS  Google Scholar 

  42. Wang G, Wang W, Zhang Y, Gou X, Zhang Q, Huang Y, et al. Ethanol changes Nestin-promoter induced neural stem cells to disturb newborn dendritic spine remodeling in the hippocampus of mice. Neural Regen Res. 2024;19:416–24.

    PubMed  CAS  Google Scholar 

  43. Han W, Wang F, Qi J, Wang F, Zhang L, Zhao S, et al. NMDA receptors in the medial prefrontal cortex and the dorsal hippocampus regulate methamphetamine-induced hyperactivity and extracellular amino acid release in mice. Behav Brain Res. 2012;232:44–52.

    PubMed  CAS  Google Scholar 

  44. Leng H, Zhang X, Wang Q, Luan X, Sun X, Guo F, et al. Regulation of stress-induced gastric ulcers via central oxytocin and a potential mechanism through the VTA-NAc dopamine pathway. Neurogastroenterol Motil. 2019;31:e13655.

    PubMed  Google Scholar 

  45. Zhang RR, Cui QY, Murai K, Lim YC, Smith ZD, Jin S, et al. Tet1 regulates adult hippocampal neurogenesis and cognition. Cell Stem Cell. 2013;13:237–45.

    PubMed  PubMed Central  Google Scholar 

  46. Ladron de Guevara-Miranda D, Moreno-Fernandez RD, Gil-Rodriguez S, Rosell-Valle C, Estivill-Torrus G, Serrano A, et al. Lysophosphatidic acid-induced increase in adult hippocampal neurogenesis facilitates the forgetting of cocaine-contextual memory. Addict Biol. 2019;24:458–70.

    PubMed  CAS  Google Scholar 

  47. Dogbevia GK, Robetamanith M, Sprengel R, Hasan MT. Flexible, AAV-equipped genetic modules for inducible control of gene expression in mammalian brain. Mol Ther Nucleic Acids. 2016;5:e309.

    PubMed  PubMed Central  CAS  Google Scholar 

  48. Hasan MT, Althammer F, Silva da Gouveia M, Goyon S, Eliava M, Lefevre A, et al. A fear memory engram and its plasticity in the hypothalamic oxytocin system. Neuron. 2019;103:133–46 e138.

    PubMed  CAS  Google Scholar 

  49. Rotheneichner P, Romanelli P, Bieler L, Pagitsch S, Zaunmair P, Kreutzer C, et al. Tamoxifen activation of cre-recombinase has no persisting effects on adult neurogenesis or learning and anxiety. Front Neurosci. 2017;11:27.

    PubMed  PubMed Central  Google Scholar 

  50. Paxinos G, Franklin KBJ. Paxinos and Franklin’s the mouse brain in stereotaxic coordinates. 5th Edition. San Diego: Elsevier Academic Press; 2019.

  51. Zhang Z, Yang J, Liu C, Xie J, Qiu S, Yang X, et al. Pseudoginsenoside-F11 alleviates cognitive deficits and Alzheimer’s disease-type pathologies in SAMP8 mice. Pharmacol Res. 2019;139:512–23.

    PubMed  CAS  Google Scholar 

  52. Zhu H, Pleil KE, Urban DJ, Moy SS, Kash TL, Roth BL. Chemogenetic inactivation of ventral hippocampal glutamatergic neurons disrupts consolidation of contextual fear memory. Neuropsychopharmacology. 2014;39:1880–92.

    PubMed  PubMed Central  CAS  Google Scholar 

  53. Cuartero MI, de la Parra J, Perez-Ruiz A, Bravo-Ferrer I, Duran-Laforet V, Garcia-Culebras A, et al. Abolition of aberrant neurogenesis ameliorates cognitive impairment after stroke in mice. J Clin Invest. 2019;129:1536–50.

    PubMed  PubMed Central  Google Scholar 

  54. Chen BK, Murawski NJ, Cincotta C, McKissick O, Finkelstein A, Hamidi AB, et al. Artificially enhancing and suppressing hippocampus-mediated memories. Curr Biol. 2019;29:1885–94.e1884.

    PubMed  PubMed Central  CAS  Google Scholar 

  55. Yuan L, Sun S, Pan X, Zheng L, Li Y, Yang J, et al. Pseudoginsenoside-F11 improves long-term neurological function and promotes neurogenesis after transient cerebral ischemia in mice. Neurochem Int. 2020;133:104586.

    PubMed  CAS  Google Scholar 

  56. Marco A, Meharena HS, Dileep V, Raju RM, Davila-Velderrain J, Zhang AL, et al. Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble. Nat Neurosci. 2020;23:1606–17.

    PubMed  PubMed Central  CAS  Google Scholar 

  57. Lin YT, Chen CC, Huang CC, Nishimori K, Hsu KS. Oxytocin stimulates hippocampal neurogenesis via oxytocin receptor expressed in CA3 pyramidal neurons. Nat Commun. 2017;8:537.

    PubMed  PubMed Central  Google Scholar 

  58. Kempermann G, Song H, Gage FH. Adult neurogenesis in the hippocampus. Hippocampus. 2023;33:269–70.

    PubMed  PubMed Central  Google Scholar 

  59. Mishra R, Phan T, Kumar P, Morrissey Z, Gupta M, Hollands C, et al. Augmenting neurogenesis rescues memory impairments in Alzheimer’s disease by restoring the memory-storing neurons. J Exp Med. 2022;219:e20220391.

    PubMed  PubMed Central  CAS  Google Scholar 

  60. Chen R, Wang Z, Lin Q, Hou X, Jiang Y, Le Q, et al. Destabilization of fear memory by Rac1-driven engram-microglia communication in hippocampus. Brain Behav Immun. 2024;119:621–36.

    PubMed  CAS  Google Scholar 

  61. Ramirez S, Liu X, MacDonald CJ, Moffa A, Zhou J, Redondo RL, et al. Activating positive memory engrams suppresses depression-like behaviour. Nature. 2015;522:335–9.

    PubMed  PubMed Central  CAS  Google Scholar 

  62. Galinato MH, Takashima Y, Fannon MJ, Quach LW, Morales Silva RJ, Mysore KK, et al. Neurogenesis during abstinence is necessary for context-driven methamphetamine-related memory. J Neurosci. 2018;38:2029–42.

    PubMed  PubMed Central  CAS  Google Scholar 

  63. Calpe-Lopez C, Garcia-Pardo MP, Aguilar MA. Cannabidiol treatment might promote resilience to cocaine and methamphetamine use disorders: a review of possible mechanisms. Molecules. 2019;24:2583.

    PubMed  PubMed Central  CAS  Google Scholar 

  64. Jiang C, Xu Y, Zhong J, Wu J, He J, Xu W, et al. Chloral hydrate alters brain activation induced by methamphetamine-associated cue and prevents relapse. Front Mol Neurosci. 2022;15:934167.

    PubMed  PubMed Central  CAS  Google Scholar 

  65. Xue YX, Luo YX, Wu P, Shi HS, Xue LF, Chen C, et al. A memory retrieval-extinction procedure to prevent drug craving and relapse. Science. 2012;336:241–5.

    PubMed  PubMed Central  CAS  Google Scholar 

  66. Cox BM, Young AB, See RE, Reichel CM. Sex differences in methamphetamine seeking in rats: impact of oxytocin. Psychoneuroendocrinology. 2013;38:2343–53.

    PubMed  PubMed Central  CAS  Google Scholar 

  67. Qian H, Shang Q, Liang M, Gao B, Xiao J, Wang J, et al. MicroRNA-31-3p/RhoA signaling in the dorsal hippocampus modulates methamphetamine-induced conditioned place preference in mice. Psychopharmacology. 2021;238:3207–19.

    PubMed  CAS  Google Scholar 

  68. Mohammadi M, Eskandari K, Azizbeigi R, Haghparast A. The inhibitory effect of cannabidiol on the rewarding properties of methamphetamine in part mediates by interacting with the hippocampal D1-like dopamine receptors. Prog Neuropsychopharmacol Biol Psychiatry. 2023;126:110778.

    PubMed  CAS  Google Scholar 

  69. Epp JR, Silva Mera R, Kohler S, Josselyn SA, Frankland PW. Neurogenesis-mediated forgetting minimizes proactive interference. Nat Commun. 2016;7:10838.

    PubMed  PubMed Central  CAS  Google Scholar 

  70. Mandyam CD, Wee S, Crawford EF, Eisch AJ, Richardson HN, Koob GF. Varied access to intravenous methamphetamine self-administration differentially alters adult hippocampal neurogenesis. Biol Psychiatry. 2008;64:958–65.

    PubMed  PubMed Central  CAS  Google Scholar 

  71. Razavi Y, Keyhanfar F, Haghparast A, Shabani R, Mehdizadeh M. Cannabidiol promotes neurogenesis in the dentate gyrus during an abstinence period in rats following chronic exposure to methamphetamine. Metab Brain Dis. 2021;36:1381–90.

    PubMed  CAS  Google Scholar 

  72. Castilla-Ortega E, Blanco E, Serrano A, Ladron de Guevara-Miranda D, Pedraz M, Estivill-Torrus G, et al. Pharmacological reduction of adult hippocampal neurogenesis modifies functional brain circuits in mice exposed to a cocaine conditioned place preference paradigm. Addict Biol. 2016;21:575–88.

    PubMed  CAS  Google Scholar 

  73. Ishikawa R, Fukushima H, Frankland PW, Kida S. Hippocampal neurogenesis enhancers promote forgetting of remote fear memory after hippocampal reactivation by retrieval. Elife. 2016;5:e17464.

    PubMed  PubMed Central  Google Scholar 

  74. Raj B, Farrell JA, Liu J, El Kholtei J, Carte AN, Navajas Acedo J, et al. Emergence of neuronal diversity during vertebrate brain development. Neuron. 2020;108:1058–74.e1056.

    PubMed  PubMed Central  CAS  Google Scholar 

  75. Leuner B, Caponiti JM, Gould E. Oxytocin stimulates adult neurogenesis even under conditions of stress and elevated glucocorticoids. Hippocampus. 2012;22:861–8.

    PubMed  CAS  Google Scholar 

  76. Kee N, Teixeira CM, Wang AH, Frankland PW. Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nat Neurosci. 2007;10:355–62.

    PubMed  CAS  Google Scholar 

  77. Piatti VC, Davies-Sala MG, Esposito MS, Mongiat LA, Trinchero MF, Schinder AF. The timing for neuronal maturation in the adult hippocampus is modulated by local network activity. J Neurosci. 2011;31:7715–28.

    PubMed  PubMed Central  CAS  Google Scholar 

  78. Song J, Sun J, Moss J, Wen Z, Sun GJ, Hsu D, et al. Parvalbumin interneurons mediate neuronal circuitry-neurogenesis coupling in the adult hippocampus. Nat Neurosci. 2013;16:1728–30.

    PubMed  PubMed Central  CAS  Google Scholar 

  79. Matos MR, Visser E, Kramvis I, van der Loo RJ, Gebuis T, Zalm R, et al. Memory strength gates the involvement of a CREB-dependent cortical fear engram in remote memory. Nat Commun. 2019;10:2315.

    PubMed  PubMed Central  Google Scholar 

  80. Mu Y, Gage FH. Adult hippocampal neurogenesis and its role in Alzheimer’s disease. Mol Neurodegener. 2011;6:85.

    PubMed  PubMed Central  Google Scholar 

  81. Frankland PW, Kohler S, Josselyn SA. Hippocampal neurogenesis and forgetting. Trends Neurosci. 2013;36:497–503.

    PubMed  CAS  Google Scholar 

  82. Zhou Y, Yan E, Cheng D, Zhu H, Liu Z, Chen X, et al. The projection from ventral CA1, not prefrontal cortex, to nucleus accumbens core mediates recent memory retrieval of cocaine-conditioned place preference. Front Behav Neurosci. 2020;14:558074.

    PubMed  PubMed Central  CAS  Google Scholar 

  83. Legault M, Rompre PP, Wise RA. Chemical stimulation of the ventral hippocampus elevates nucleus accumbens dopamine by activating dopaminergic neurons of the ventral tegmental area. J Neurosci. 2000;20:1635–42.

    PubMed  PubMed Central  CAS  Google Scholar 

  84. Todd CL, Grace AA. Modulation of ventral tegmental area dopamine cell activity by the ventral subiculum and entorhinal cortex. Ann N Y Acad Sci. 1999;877:688–90.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The present research was supported by the National Natural Science Foundation of China (82273916) from Jingyu Yang, the National Natural Science Foundation of China Youth Fund Project (82204373), the Youth Scientific Research Project of Educational Commission of Liaoning Province (JYTQN2023320), the General Project of Liaoning Provincial Department of Science and Technology (2024-MSLH-427) and the Youqing Support Project of Shenyang Pharmaceutical University (YQ202201) from Xiaohang Che. The graphic abstract was created with the help of Adobe Illustrator CS6 software.

Author information

Author notes

  1. These authors contributed equally: Jialing Cai, Xiaohang Che.

Authors and Affiliations

  1. Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, PR China

    Jialing Cai, Xiaohang Che, Yanling Deng, Zhenkun Guo, Meixue Yin, Xincheng Li, Xiaoling Liu, Yuanchao Luo, Tianyu Xu, Wenzhe Zhu, Nina An, Yijun Bai, Chunfu Wu & Jingyu Yang

  2. Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, PR China

    Yuting Li

Authors
  1. Jialing Cai
    View author publications

    Search author on:PubMed Google Scholar

  2. Xiaohang Che
    View author publications

    Search author on:PubMed Google Scholar

  3. Yanling Deng
    View author publications

    Search author on:PubMed Google Scholar

  4. Zhenkun Guo
    View author publications

    Search author on:PubMed Google Scholar

  5. Meixue Yin
    View author publications

    Search author on:PubMed Google Scholar

  6. Yuting Li
    View author publications

    Search author on:PubMed Google Scholar

  7. Xincheng Li
    View author publications

    Search author on:PubMed Google Scholar

  8. Xiaoling Liu
    View author publications

    Search author on:PubMed Google Scholar

  9. Yuanchao Luo
    View author publications

    Search author on:PubMed Google Scholar

  10. Tianyu Xu
    View author publications

    Search author on:PubMed Google Scholar

  11. Wenzhe Zhu
    View author publications

    Search author on:PubMed Google Scholar

  12. Nina An
    View author publications

    Search author on:PubMed Google Scholar

  13. Yijun Bai
    View author publications

    Search author on:PubMed Google Scholar

  14. Chunfu Wu
    View author publications

    Search author on:PubMed Google Scholar

  15. Jingyu Yang
    View author publications

    Search author on:PubMed Google Scholar

Contributions

CJL and CXH contributed equally to this work. CJL, CXH, LYT, YJY and WCF contributed to the conception and design of the present study. CJL, CXH, DYL, GZK, YMX, LXC, ZWZ, ANN and BYJ performed the experiment. LXL, LYC and XTY performed the statistical analysis of the experimental data. CJL and CXH wrote the first draft of the manuscript. DYL and YMX wrote the sections of the manuscript. All authors contributed to manuscript revision, read and approved the submitted version.

Corresponding authors

Correspondence to Chunfu Wu or Jingyu Yang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

All methods performed in this study were conducted in accordance with the relevant guidelines and regulations. Ethical approval was obtained from the Experimental Animal Research Committee of Shenyang Pharmaceutical University and performed in accordance to the Guidelines for Care and Use of Laboratory Animals (Registration no. SYPU-IACUC-GZR2020-04.13-110). The study does not include human participants. The study does not include data from humans.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cai, J., Che, X., Deng, Y. et al. Oxytocin attenuates the retrieval of methamphetamine-associated reward memories by enhancing adult hippocampal neurogenesis in mice. Mol Psychiatry 30, 5664–5679 (2025). https://doi.org/10.1038/s41380-025-03222-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41380-025-03222-7

Search

Advanced search

Quick links