Skip to main content

Advertisement

SpringerLink
Log in

The selective TAAR1 partial agonist RO5263397 promoted novelty recognition memory in mice

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor that has a particular role in regulating dopaminergic, serotonergic, and glutamatergic transmission. TAAR1 agonists have shown pro-cognitive activities. However, it remains largely unknown of the effects of TAAR1 agonists on memory performance.

Objectives

Here, by using the mice novel object recognition (NOR) test, we examined the effects of the selective TAAR1 partial agonist RO5263397 on recognition memory.

Results

We found that RO5263397 significantly enhanced the retrieval of short-term memory (STM; 20 min after training) both in male and female mice. RO5263397 promoted the retrieval of STM in the wild-type (WT) littermates but not TAAR1-KO mice, indicating that the effects of RO5263397 were dependent on TAAR1. Interestingly, compared to their WT litters, TAAR1-KO mice showed similar levels of STM, suggesting that genetic deletion of taar1 gene did not affect the STM retrieval. Furthermore, RO5263397 also promoted the retrieval of long-term NOR memory (24 h after training).

Conclusions

These results indicate that TAAR1 activation promotes NOR memory retrieval. Consistent with previous studies, our finding further suggests that TAAR1 agonists have pro-cognitive properties.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Aben B, Stapert S, Blokland A (2012) About the distinction between working memory and short-term memory. Front Psychol 3:301

    Article  PubMed  PubMed Central  Google Scholar 

  • Accorroni A, Rutigliano G, Sabatini M, Frascarelli S, Borso M, Novelli E, Bandini L, Ghelardoni S, Saba A, Zucchi R, Origlia N (2020) Exogenous 3-iodothyronamine rescues the entorhinal cortex from beta-amyloid toxicity. Thyroid 30:147–160

    Article  PubMed  CAS  Google Scholar 

  • Achat-Mendes C, Lynch LJ, Sullivan KA, Vallender EJ, Miller GM (2012) Augmentation of methamphetamine-induced behaviors in transgenic mice lacking the trace amine-associated receptor 1. Pharmacol Biochem Behav 101:201–207

    Article  PubMed  CAS  Google Scholar 

  • Antunes M, Biala G (2012) The novel object recognition memory: neurobiology, test procedure, and its modifications. Cogn Process 13:93–110

    Article  PubMed  CAS  Google Scholar 

  • Berry MD (2007) The potential of trace amines and their receptors for treating neurological and psychiatric diseases. Rev Recent Clin Trials 2:3–19

    Article  PubMed  CAS  Google Scholar 

  • Berry MD, Gainetdinov RR, Hoener MC, Shahid M (2017) Pharmacology of human trace amine-associated receptors: therapeutic opportunities and challenges. Pharmacol Ther 180:161–180

    Article  PubMed  CAS  Google Scholar 

  • Burchett SA, Hicks TP (2006) The mysterious trace amines: protean neuromodulators of synaptic transmission in mammalian brain. Prog Neurobiol 79:223–246

    Article  PubMed  CAS  Google Scholar 

  • Cisneros IE, Ghorpade A (2014) Methamphetamine and HIV-1-induced neurotoxicity: role of trace amine associated receptor 1 cAMP signaling in astrocytes. Neuropharmacology 85:499–507

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cowan N (2008) What are the differences between long-term, short-term, and working memory? Prog Brain Res 169:323–338

    Article  PubMed  PubMed Central  Google Scholar 

  • Damiana Leo SE, Agnes Villers, Raul Gainetdinov, Laurence Ris (2019) Trace amine associate receptor 1 (TAAR1) as a new target for the treatment of cognitive dysfunction in Alzheimer disease. Front Neurosci Conference Abstract: 13th National Congress of the Belgian Society for Neuroscience

  • Davis RL, Zhong Y (2017) The Biology of Forgetting-A Perspective. Neuron 95:490–503

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Di Cara B, Maggio R, Aloisi G, Rivet JM, Lundius EG, Yoshitake T, Svenningsson P, Brocco M, Gobert A, De Groote L, Cistarelli L, Veiga S, De Montrion C, Rodriguez M, Galizzi JP, Lockhart BP, Coge F, Boutin JA, Vayer P, Verdouw PM, Groenink L, Millan MJ (2011) Genetic deletion of trace amine 1 receptors reveals their role in auto-inhibiting the actions of ecstasy (MDMA). J Neurosci 31:16928–16940

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ebbinghaus H (2013) Memory: a contribution to experimental psychology. Ann Neurosci 20:155–156

    Article  PubMed  Google Scholar 

  • Ennaceur A (2010) One-trial object recognition in rats and mice: methodological and theoretical issues. Behav Brain Res 215:244–254

    Article  PubMed  CAS  Google Scholar 

  • Ennaceur A, Delacour J (1988) A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data. Behav Brain Res 31:47–59

    Article  PubMed  CAS  Google Scholar 

  • Ennaceur A, Meliani K (1992) A new one-trial test for neurobiological studies of memory in rats. III. Spatial vs. non-spatial working memory. Behav Brain Res 51:83–92

    Article  PubMed  CAS  Google Scholar 

  • Espinoza S, Lignani G, Caffino L, Maggi S, Sukhanov I, Leo D, Mus L, Emanuele M, Ronzitti G, Harmeier A, Medrihan L, Sotnikova TD, Chieregatti E, Hoener MC, Benfenati F, Tucci V, Fumagalli F, Gainetdinov RR (2015) TAAR1 modulates cortical glutamate NMDA receptor function. Neuropsychopharmacology 40:2217–2227

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gainetdinov RR, Hoener MC, Berry MD (2018) Trace amines and their receptors. Pharmacol Rev 70:549–620

    Article  PubMed  CAS  Google Scholar 

  • Gale SD, Baxter L, Thompson J (2016) Greater memory impairment in dementing females than males relative to sex-matched healthy controls. J Clin Exp Neuropsychol 38:527–533

    Article  PubMed  PubMed Central  Google Scholar 

  • Goodman J, Packard MG (2016) Memory Systems and the Addicted Brain. Front Psychiatry 7:24

    Article  PubMed  PubMed Central  Google Scholar 

  • Goonawardena AV, Morairty SR, Dell R, Orellana GA, Hoener MC, Wallace TL, Kilduff TS (2019) Trace amine-associated receptor 1 agonism promotes wakefulness without impairment of cognition in Cynomolgus macaques. Neuropsychopharmacology 44:1485–1493

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Goulart BK, de Lima MN, de Farias CB, Reolon GK, Almeida VR, Quevedo J, Kapczinski F, Schroder N, Roesler R (2010) Ketamine impairs recognition memory consolidation and prevents learning-induced increase in hippocampal brain-derived neurotrophic factor levels. Neuroscience 167:969–973

    Article  PubMed  CAS  Google Scholar 

  • Hammond RS, Tull LE, Stackman RW (2004) On the delay-dependent involvement of the hippocampus in object recognition memory. Neurobiol Learn Mem 82:26–34

    Article  PubMed  Google Scholar 

  • Herlitz A, Nilsson LG, Backman L (1997) Gender differences in episodic memory. Mem Cognit 25:801–811

    Article  PubMed  CAS  Google Scholar 

  • Jonides J, Lewis RL, Nee DE, Lustig CA, Berman MG, Moore KS (2008) The mind and brain of short-term memory. Annu Rev Psychol 59:193–224

    Article  PubMed  PubMed Central  Google Scholar 

  • Kolb B, Whishaw IQ (1996) Fundamentals of human neuropsychology, 4th edn. W.H. Freeman, New York

    Google Scholar 

  • Leger M, Quiedeville A, Bouet V, Haelewyn B, Boulouard M, Schumann-Bard P, Freret T (2013) Object recognition test in mice. Nat Protoc 8:2531–2537

    Article  PubMed  CAS  Google Scholar 

  • Lindemann L, Meyer CA, Jeanneau K, Bradaia A, Ozmen L, Bluethmann H, Bettler B, Wettstein JG, Borroni E, Moreau JL, Hoener MC (2008) Trace amine-associated receptor 1 modulates dopaminergic activity. J Pharmacol Exp Ther 324:948–956

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Seaman R Jr, Johnson B, Wu R, Vu J, Tian J, Zhang Y, Li JX (2021) Activation of trace amine-associated receptor 1 selectively attenuates the reinforcing effects of morphine. Br J Pharmacol 178:933–945

    Article  PubMed  CAS  Google Scholar 

  • Liu JF, Li JX (2018) TAAR1 in Addiction: Looking Beyond the Tip of the Iceberg. Front Pharmacol 9:279

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu JF, Seaman R Jr, Siemian JN, Bhimani R, Johnson B, Zhang Y, Zhu Q, Hoener MC, Park J, Dietz DM, Li JX (2018) Role of trace amine-associated receptor 1 in nicotine’s behavioral and neurochemical effects. Neuropsychopharmacology 43:2435–2444

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu JF, Thorn DA, Zhang Y, Li JX (2016) Effects of trace amine-associated receptor 1 agonists on the expression, reconsolidation, and extinction of cocaine reward memory. Int J Neuropsychopharmacol 19

  • Manni ME, De Siena G, Saba A, Marchini M, Landucci E, Gerace E, Zazzeri M, Musilli C, Pellegrini-Giampietro D, Matucci R, Zucchi R, Raimondi L (2013) Pharmacological effects of 3-iodothyronamine (T1AM) in mice include facilitation of memory acquisition and retention and reduction of pain threshold. Br J Pharmacol 168:354–362

    Article  PubMed  CAS  Google Scholar 

  • Pauls F, Petermann F, Lepach AC (2013) Gender differences in episodic memory and visual working memory including the effects of age. Memory 21:857–874

    Article  PubMed  Google Scholar 

  • Pei Y, Asif-Malik A, Canales JJ (2016) Trace amines and the trace amine-associated receptor 1: Pharmacology, Neurochemistry, and Clinical Implications. Front Neurosci 10:148

    Article  PubMed  PubMed Central  Google Scholar 

  • Revel FG, Moreau JL, Gainetdinov RR, Bradaia A, Sotnikova TD, Mory R, Durkin S, Zbinden KG, Norcross R, Meyer CA, Metzler V, Chaboz S, Ozmen L, Trube G, Pouzet B, Bettler B, Caron MG, Wettstein JG, Hoener MC (2011) TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity. Proc Natl Acad Sci U S A 108:8485–8490

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Revel FG, Moreau JL, Gainetdinov RR, Ferragud A, Velazquez-Sanchez C, Sotnikova TD, Morairty SR, Harmeier A, Groebke Zbinden K, Norcross RD, Bradaia A, Kilduff TS, Biemans B, Pouzet B, Caron MG, Canales JJ, Wallace TL, Wettstein JG, Hoener MC (2012) Trace amine-associated receptor 1 partial agonism reveals novel paradigm for neuropsychiatric therapeutics. Biol Psychiatry 72:934–942

    Article  PubMed  CAS  Google Scholar 

  • Revel FG, Moreau JL, Pouzet B, Mory R, Bradaia A, Buchy D, Metzler V, Chaboz S, Groebke Zbinden K, Galley G, Norcross RD, Tuerck D, Bruns A, Morairty SR, Kilduff TS, Wallace TL, Risterucci C, Wettstein JG, Hoener MC (2013) A new perspective for schizophrenia: TAAR1 agonists reveal antipsychotic- and antidepressant-like activity, improve cognition and control body weight. Mol Psychiatry 18:543–556

    Article  PubMed  CAS  Google Scholar 

  • Rutigliano G, Accorroni A, Zucchi R (2017) The Case for TAAR1 as a Modulator of Central Nervous System Function. Front Pharmacol 8:987

    Article  PubMed  CAS  Google Scholar 

  • Sara SJ (2000) Strengthening the shaky trace through retrieval. Nat Rev Neurosci 1:212–213

    Article  PubMed  CAS  Google Scholar 

  • Silvers JM, Harrod SB, Mactutus CF, Booze RM (2007) Automation of the novel object recognition task for use in adolescent rats. J Neurosci Methods 166:99–103

    Article  PubMed  PubMed Central  Google Scholar 

  • Taglialatela G, Hogan D, Zhang WR, Dineley KT (2009) Intermediate- and long-term recognition memory deficits in Tg2576 mice are reversed with acute calcineurin inhibition. Behav Brain Res 200:95–99

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Thorn DA, Jing L, Qiu Y, Gancarz-Kausch AM, Galuska CM, Dietz DM, Zhang Y, Li JX (2014) Effects of the trace amine-associated receptor 1 agonist RO5263397 on abuse-related effects of cocaine in rats. Neuropsychopharmacology 39:2309–2316

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • White NM (1996) Addictive drugs as reinforcers: multiple partial actions on memory systems. Addiction 91: 921–49; discussion 951–65

  • Wolinsky TD, Swanson CJ, Smith KE, Zhong H, Borowsky B, Seeman P, Branchek T, Gerald CP (2007) The Trace Amine 1 receptor knockout mouse: an animal model with relevance to schizophrenia. Genes Brain Behav 6:628–639

    Article  PubMed  CAS  Google Scholar 

  • Wu R, Liu J, Wang K, Huang Y, Zhang Y, Li JX (2020) Effects of a trace amine-associated receptor 1 agonist RO 5263397 on ethanol-induced behavioral sensitization. Behav Brain Res 390:112641

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang Y, Li JT, Wang H, Niu WP, Zhang CC, Zhang Y, Wang XD, Si TM, Su YA (2021) Role of trace amineassociated receptor 1 in the medial prefrontal cortex in chronic social stress-induced cognitive deficits in mice. Pharmacol Res 167:105571

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr. Gregory M Miller at Northeastern University (Boston, MA, USA) for providing with us the breeding pairs of TAAR1 knockout mice.

Funding

This work was supported by the National Institutes of Health National Institute on Drug Abuse (grant number R01DA047967 to J-X.L.).

Author information

Author notes

  1. Ruyan Wu, Jianfeng Liu, and Robert Seaman Jr contributed equally.

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University At Buffalo, The State University of New York, 955 Main Street, Buffalo, NY, 14214, USA

    Ruyan Wu, Jianfeng Liu, Robert Seaman Jr, Bernard Johnson & Jun-Xu Li

  2. Medical College of Yangzhou University, Yangzhou, China

    Ruyan Wu

  3. Research Triangle Institute, Research Triangle Park, NC, USA

    Yanan Zhang

Authors
  1. Ruyan Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jianfeng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert Seaman Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bernard Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yanan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jun-Xu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

R.W., J. L., and J-X.L. designed the study; R.W., J. L., R.S., and B.J. conducted experiments; Y.Z. provided the TAAR1 agonist RO5263397; R.W., J.L., and J-X.L. prepared the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Jun-Xu Li.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Disclaimer

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, R., Liu, J., Seaman, R. et al. The selective TAAR1 partial agonist RO5263397 promoted novelty recognition memory in mice. Psychopharmacology 238, 3221–3228 (2021). https://doi.org/10.1007/s00213-021-05937-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-021-05937-1

Keywords

Search

Navigation