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Differential Roles of Intra-accumbal Orexin Receptors in Acquisition and Expression of Methamphetamine-Induced Conditioned Place Preference in the Rats

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A large amount of document has revealed that the orexin system in the reward circuity, including the nucleus accumbens (NAc), contributes to the modification of drug reinforcement. It has proven that the orexin receptors (OXRs) are expressed on dopamine terminals in the NAc; therefore, it can modulate reward-related behaviors. In the present study, the conditioned place preference (CPP) paradigm was used to evaluate the role of OXRs in the NAc in the acquisition and expression of methamphetamine (METH)-induced CPP. Based on previous studies, animals received METH (1 mg/kg; sc) on a 5-day schedule to induce CPP. The rats bilaterally received SB334867, OX1R antagonist, or TCS OX2 29, OX2R antagonist, (1, 10, and 30 nM/0.5 µl DMSO 12%) over five days of conditioning by METH to display the role of OXRs in reward acquisition. Moreover, the rats bilaterally received SB334867 or TCS OX2 29 in the NAc before the post-conditioning test to consider the impact of OXR antagonists on the expression of METH-induced CPP. The data revealed that the administration of SB334867 or TCS OX2 29 in the NAc led to a decrease in the acquisition of METH-induced CPP. Additionally, intra-accumbal injection of OX1R antagonist inhibited the expression of METH-induced CPP, while the OX2R antagonist failed to change this expression. Finally, the intra-NAc microinjection of both OXR antagonists was more effective in inhibiting acquisition than blocking the expression phase of METH. Data from the current study confirms that OXRs in the NAc regulate the reward-related effects of METH.

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References

  1. Morais APD, Pita IR, Fontes-Ribeiro CA, Pereira FC (2018) The neurobiological mechanisms of physical exercise in methamphetamine addiction. CNS Neurosci Ther 24:85–97

    PubMed  Google Scholar 

  2. Koob GF, Volkow ND (2016) Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry 3:760–773

    PubMed  PubMed Central  Google Scholar 

  3. Luscher C, Malenka RC (2011) Drug-evoked synaptic plasticity in addiction: from molecular changes to circuit remodeling. Neuron 69:650–663

    PubMed  PubMed Central  Google Scholar 

  4. Mieda M, Yanagisawa M (2002) Sleep, feeding, and neuropeptides: roles of orexins and orexin receptors. Curr Opin Neurobiol 12:339–345

    CAS  PubMed  Google Scholar 

  5. Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18:9996–10015

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92:573–585

    CAS  PubMed  Google Scholar 

  7. D’Almeida V, Hipolide DC, Raymond R, Barlow KB, Parkes JH, Pedrazzoli M, Tufik S, Nobrega JN (2005) Opposite effects of sleep rebound on orexin OX1 and OX2 receptor expression in rat brain. Brain Res Mol Brain Res 136:148–157

    PubMed  Google Scholar 

  8. Marcus JN, Aschkenasi CJ, Lee CE, Chemelli RM, Saper CB, Yanagisawa M, Elmquist JK (2001) Differential expression of orexin receptors 1 and 2 in the rat brain. J Comp Neurol 435:6–25

    CAS  PubMed  Google Scholar 

  9. Mukai K, Kim J, Nakajima K, Oomura Y, Wayner MJ, Sasaki K (2009) Electrophysiological effects of orexin/hypocretin on nucleus accumbens shell neurons in rats: an in vitro study. Peptides 30:1487–1496

    CAS  PubMed  Google Scholar 

  10. Bentzley BS, Aston-Jones G (2015) Orexin-1 receptor signaling increases motivation for cocaine-associated cues. Eur J Neurosci 41:1149–1156

    PubMed  PubMed Central  Google Scholar 

  11. Espana RA, Melchior JR, Roberts DC, Jones SR (2011) Hypocretin 1/orexin A in the ventral tegmental area enhances dopamine responses to cocaine and promotes cocaine self-administration. Psychopharmacology 214:415–426

    CAS  PubMed  Google Scholar 

  12. Gentile TA, Simmons SJ, Barker DJ, Shaw JK, Espana RA, Muschamp JW (2018) Suvorexant, an orexin/hypocretin receptor antagonist, attenuates motivational and hedonic properties of cocaine. Addict Biol 23:247–255

    CAS  PubMed  Google Scholar 

  13. Quarta D, Valerio E, Hutcheson DM, Hedou G, Heidbreder C (2010) The orexin-1 receptor antagonist SB-334867 reduces amphetamine-evoked dopamine outflow in the shell of the nucleus accumbens and decreases the expression of amphetamine sensitization. Neurochem Int 56:11–15

    CAS  PubMed  Google Scholar 

  14. Shaw JK, Ferris MJ, Locke JL, Brodnik ZD, Jones SR, Espana RA (2017) Hypocretin/orexin knock-out mice display disrupted behavioral and dopamine responses to cocaine. Addict Biol 22:1695–1705

    CAS  PubMed  Google Scholar 

  15. Steiner MA, Lecourt H, Jenck F (2013) The dual orexin receptor antagonist almorexant, alone and in combination with morphine, cocaine and amphetamine, on conditioned place preference and locomotor sensitization in the rat. Int J Neuropsychopharmacol 16:417–432

    CAS  PubMed  Google Scholar 

  16. Karimi-Haghighi S, Haghparast A (2018) Cannabidiol inhibits priming-induced reinstatement of methamphetamine in REM sleep deprived rats. Prog Neuropsychopharmacol Biol Psychiatry 82:307–313

    CAS  PubMed  Google Scholar 

  17. Attarzadeh-Yazdi G, Arezoomandan R, Haghparast A (2014) Minocycline, an antibiotic with inhibitory effect on microglial activation, attenuates the maintenance and reinstatement of methamphetamine-seeking behavior in rat. Prog Neuropsychopharmacol Biol Psychiatry 53:142–148

    CAS  PubMed  Google Scholar 

  18. Farzinpour Z, Taslimi Z, Azizbeigi R, Karimi-Haghighi S, Haghparast A (2019) Involvement of orexinergic receptors in the nucleus accumbens, in the effect of forced swim stress on the reinstatement of morphine seeking behaviors. Behav Brain Res 356:279–287

    CAS  PubMed  Google Scholar 

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

    Google Scholar 

  20. Karimi-Haghighi S, Dargahi L, Haghparast A (2019) Cannabidiol modulates the expression of neuroinflammatory factors in stress- and drug-induced reinstatement of methamphetamine in extinguished rats. Addict Biol

  21. Arezoomandan R, Moradi M, Attarzadeh-Yazdi G, Tomaz C, Haghparast A (2016) Administration of activated glial condition medium in the nucleus accumbens extended extinction and intensified reinstatement of methamphetamine-induced conditioned place preference. Brain Res Bull 125:106–116

    CAS  PubMed  Google Scholar 

  22. Bayat AH, Haghparast A (2015) Effect of insulin deficiency on the rewarding properties of methamphetamine in streptozotocin-induced diabetic rats. Pharmacol Biochem Behav 128:8–13

    CAS  PubMed  Google Scholar 

  23. Alizamini MM, Farzinpour Z, Ezzatpanah S, Haghparast A (2017) Role of intra-accumbal orexin receptors in the acquisition of morphine-induced conditioned place preference in the rats. Neurosci Lett 660:1–5

    CAS  PubMed  Google Scholar 

  24. Seo J-Y, Ko Y-H, Ma S-X, Lee B-R, Lee S-Y, Jang C-G (2018) Repeated restraint stress reduces the acquisition and relapse of methamphetamine-conditioned place preference but not behavioral sensitization. Brain Res Bull 139:99–104

    CAS  PubMed  Google Scholar 

  25. Watabe-Uchida M, Zhu L, Ogawa SK, Vamanrao A, Uchida N (2012) Whole-brain mapping of direct inputs to midbrain dopamine neurons. Neuron 74:858–873

    CAS  PubMed  Google Scholar 

  26. Scofield MD, Heinsbroek JA, Gipson CD, Kupchik YM, Spencer S, Smith AC, Roberts-Wolfe D, Kalivas PW (2016) The nucleus accumbens: mechanisms of addiction across drug classes reflect the importance of glutamate homeostasis. Pharmacol Rev 68:816–871

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Pisanu A, Lecca D, Valentini V, Bahi A, Dreyer JL, Cacciapaglia F, Scifo A, Piras G, Cadoni C, Di Chiara G (2015) Impairment of acquisition of intravenous cocaine self-administration by RNA-interference of dopamine D1-receptors in the nucleus accumbens shell. Neuropharmacology 89:398–411

    CAS  PubMed  Google Scholar 

  28. Yu J, Yan Y, Li KL, Wang Y, Huang YH, Urban NN, Nestler EJ, Schluter OM, Dong Y (2017) Nucleus accumbens feedforward inhibition circuit promotes cocaine self-administration. Proc Natl Acad Sci USA 114:E8750–E8759

    CAS  PubMed  Google Scholar 

  29. Borgland SL, Taha SA, Sarti F, Fields HL, Bonci A (2006) Orexin A in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine. Neuron 49:589–601

    CAS  PubMed  Google Scholar 

  30. Espana RA, Oleson EB, Locke JL, Brookshire BR, Roberts DC, Jones SR (2010) The hypocretin-orexin system regulates cocaine self-administration via actions on the mesolimbic dopamine system. Eur J Neurosci 31:336–348

    PubMed  Google Scholar 

  31. Foltin RW, Evans SM (2018) Hypocretin/orexin antagonists decrease cocaine self-administration by female rhesus monkeys. Drug Alcohol Depend 188:318–327

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Hollander JA, Pham D, Fowler CD, Kenny PJ (2012) Hypocretin-1 receptors regulate the reinforcing and reward-enhancing effects of cocaine: pharmacological and behavioral genetics evidence. Front Behav Neurosci 6:47

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Levy KA, Brodnik ZD, Shaw JK, Perrey DA, Zhang Y, Espana RA (2017) Hypocretin receptor 1 blockade produces bimodal modulation of cocaine-associated mesolimbic dopamine signaling. Psychopharmacology 234:2761–2776

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Blomeley C, Garau C, Burdakov D (2018) Accumbal D2 cells orchestrate innate risk-avoidance according to orexin signals. Nat Neurosci 21:29–32

    CAS  PubMed  Google Scholar 

  35. Lei K, Wegner SA, Yu JH, Mototake A, Hu B, Hopf FW (2016) Nucleus Accumbens Shell and mPFC but Not Insula Orexin-1 Receptors Promote Excessive Alcohol Drinking. Front Neurosci 10:400

    PubMed  PubMed Central  Google Scholar 

  36. Qi K, Wei C, Li Y, Sui N (2013) Orexin receptors within the nucleus accumbens shell mediate the stress but not drug priming-induced reinstatement of morphine conditioned place preference. Front Behav Neurosci 7:144

    PubMed  PubMed Central  Google Scholar 

  37. Malendowicz LK, Tortorella C, Nussdorfer GG (1999) Orexins stimulate corticosterone secretion of rat adrenocortical cells, through the activation of the adenylate cyclase-dependent signaling cascade. J Steroid Biochem Mol Biol 70:185–188

    CAS  PubMed  Google Scholar 

  38. Kukkonen JP, Åkerman KE (2005) Intracellular signal pathways utilized by the hypocretin/orexin receptors. In: Hypocretins. Springer, New York, pp 221–231

  39. Martin G, Fabre V, Siggins GR, de Lecea L (2002) Interaction of the hypocretins with neurotransmitters in the nucleus accumbens. Regul Pept 104:111–117

    CAS  PubMed  Google Scholar 

  40. Adidharma W, Deats SP, Ikeno T, Lipton JW, Lonstein JS, Yan L (2019) Orexinergic modulation of serotonin neurons in the dorsal raphe of a diurnal rodent, Arvicanthis niloticus. Horm Behav 116:104584

    CAS  PubMed  Google Scholar 

  41. Steiner N, Rossetti C, Sakurai T, Yanagisawa M, de Lecea L, Magistretti PJ, Halfon O, Boutrel B (2018) Hypocretin/orexin deficiency decreases cocaine abuse liability. Neuropharmacology 133:395–403

    CAS  PubMed  Google Scholar 

  42. Mori K, Kim J, Sasaki K (2011) Electrophysiological effects of orexin-B and dopamine on rat nucleus accumbens shell neurons in vitro. Peptides 32:246–252

    CAS  PubMed  Google Scholar 

  43. Bernstein DL, Badve PS, Barson JR, Bass CE, Espana RA (2018) Hypocretin receptor 1 knockdown in the ventral tegmental area attenuates mesolimbic dopamine signaling and reduces motivation for cocaine. Addict Biol 23:1032–1045

    CAS  PubMed  Google Scholar 

  44. Chou TC, Lee CE, Lu J, Elmquist JK, Hara J, Willie JT, Beuckmann CT, Chemelli RM, Sakurai T, Yanagisawa M, Saper CB, Scammell TE (2001) Orexin (hypocretin) neurons contain dynorphin. J Neurosci 21:Rc168

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Bruijnzeel AW (2009) kappa-Opioid receptor signaling and brain reward function. Brain Res Rev 62:127–146

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Wee S, Koob GF (2010) The role of the dynorphin-kappa opioid system in the reinforcing effects of drugs of abuse. Psychopharmacology 210:121–135

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Mori T, Nomura M, Nagase H, Narita M, Suzuki T (2002) Effects of a newly synthesized kappa-opioid receptor agonist, TRK-820, on the discriminative stimulus and rewarding effects of cocaine in rats. Psychopharmacology 161:17–22

    CAS  PubMed  Google Scholar 

  48. Takamatsu Y, Yamamoto H, Hagino Y, Markou A, Ikeda K (2011) The Selective Serotonin Reuptake Inhibitor Paroxetine, but not Fluvoxamine, Decreases Methamphetamine Conditioned Place Preference in Mice. Curr Neuropharmacol 9:68–72

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Takamatsu Y, Yamamoto H, Ogai Y, Hagino Y, Markou A, Ikeda K (2006) Fluoxetine as a potential pharmacotherapy for methamphetamine dependence: studies in mice. Ann N Y Acad Sci 1074:295–302

    CAS  PubMed  Google Scholar 

  50. Famous KR, Schmidt HD, Pierce RC (2007) When administered into the nucleus accumbens core or shell, the NMDA receptor antagonist AP-5 reinstates cocaine-seeking behavior in the rat. Neurosci Lett 420:169–173

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Prince CD, Rau AR, Yorgason JT, Espana RA (2015) Hypocretin/Orexin regulation of dopamine signaling and cocaine self-administration is mediated predominantly by hypocretin receptor 1. ACS Chem Neurosci 6:138–146

    CAS  PubMed  Google Scholar 

  52. Smith RJ, See RE, Aston-Jones G (2009) Orexin/hypocretin signaling at the orexin 1 receptor regulates cue-elicited cocaine-seeking. Eur J Neurosci 30:493–503

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the Vice-Chancellor for Research & Technology of Shahid Beheshti University of Medical Sciences (Grant No. 17852-10432/98/03/04). Also, the authors would like to thank the Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences for valuable cooperation.

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  1. Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, P.O.Box: 19615-1178, Tehran, Iran

    Elahe Khosrowabadi, Saeideh Karimi-Haghighi, Shole Jamali & Abbas Haghparast

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  1. Elahe Khosrowabadi
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Khosrowabadi, E., Karimi-Haghighi, S., Jamali, S. et al. Differential Roles of Intra-accumbal Orexin Receptors in Acquisition and Expression of Methamphetamine-Induced Conditioned Place Preference in the Rats. Neurochem Res 45, 2230–2241 (2020). https://doi.org/10.1007/s11064-020-03084-1

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