Volume 28, Issue 1 (March 2024)                   Physiol Pharmacol 2024, 28(1): 66-79 | Back to browse issues page

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Beirami E, Seyedhosseini Tamijani S M. Effects of CA1 α2-adrenergic receptors on morphine-induced exploratory behaviors. Physiol Pharmacol 2024; 28 (1) : 9
URL: http://ppj.phypha.ir/article-1-2138-en.html
Abstract:   (612 Views)
Introduction: The adrenergic and opioidergic systems play a crucial role in regulating cognitive and non-cognitive behaviors. The aim of this study was to evaluate the effects of CA1 α2-adrenoceptors on the exploratory behaviors induced by morphine.
Methods: This assessment was conducted in rats using the elevated plus-maze test based on a test-retest paradigm. Bilateral guide cannulas were stereotaxically implanted in the CA1 regions of rats to allow intra-CA1 α2-adrenoceptors agonist (clonidine) or antagonist (yohimbine) microinjections.
Results: Pre-test administration of morphine (6 mg/kg) showed an anxiolytic-like response. The extension of this effect during the retest session, 24h later, indicated impairment of aversive memory. Pre-test microinjection of clonidine (4 µg/rat) induced anxiolytic-like behavior on the test day in the absence or presence of a subthreshold dose of morphine (4 mg/kg) and increased avoidance to the open-arms during the retest session, but it was not significant compared with control group. Pre-test microinjection of yohimbine (4 µg/rat) induced an anxiogenic-like behavior on test day in the absence or presence of an effective dose of morphine (6mg/kg) and increased avoidance to the open-arms during the retest session. Concurrent microinjection of a subthreshold dose of yohimbine (1 μg/rat) with an effective dose of clonidine or with an effective dose of clonidine plus a subthreshold dose of morphine blocked anxiolytic-like behaviors, but did not change avoidance to the open-arms.
Conclusion: According to our findings, it appears that CA1 α2-adrenoceptors affect anxiolytic-like effects of morphine, but they do not appear to play a significant role in the morphine-induced memory impairment.
Article number: 9
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1. Ari C, D’Agostino DP, Diamond DM, Kindy M, Park C, Kovács Z. Elevated Plus maze test combined with video tracking software to investigate the anxiolytic effect of exogenous ketogenic supplements. J Vis Exp 2019; 143 (143): 10. [DOI:10.3791/58396]
2. Ashabi G, Oryan S, Ahmadi R, Valizadegan F. The effects of hippocampal opioidergic and septal GABAergic system interactions on anxiety-like behavior in rats. Life Sci 2011; 89 (21-22): 821-6. [DOI:10.1016/j.lfs.2011.09.009]
3. Azami NS, Piri M, Oryan S, Jahanshahi M, Babapour V, Zarrindast MR. Involvement of dorsal hippocampal alpha-adrenergic receptors in the effect of scopolamine on memory retrieval in inhibitory avoidance task. Neurobiol Learn Mem 2010; 93 (4): 455-462. [DOI:10.1016/j.nlm.2010.01.003]
4. Bashiri H, Rezayof A, Sahebgharani M, Tavangar SM, Zarrindast MR. Modulatory effects of the basolateral amygdala α2-adrenoceptors on nicotine-induced anxiogenic-like behaviours of rats in the elevated plus maze. Neuropharmacology 2016; 105: 478-486. [DOI:10.1016/j.neuropharm.2016.02.010]
5. Beirami E, Oryan S, Valizadegan F, Zarrindast MR. Performance evaluation of interference morphine and β-Adrenergic system of dorasal hippocampus on anxiety-related behaviour in male wistar rat. J Mazand Univ Med Sci 2012; 22 (91): 50-59. http://jmums.mazums.ac.ir/article-1-1300-en.html
6. Berridge CW, Arnsten AFT. Catecholamine mechanisms in the prefrontal cortex: proven strategies for enhancing higher cognitive function. Curr Opin Behav Sci 2015; 4: 33-40. [DOI:10.1016/j.cobeha.2015.01.002]
7. Bertoglio LJ, Anzini C, Lino-de-Oliveira C, Carobrez AP. Enhanced dorsolateral periaqueductal gray activity counteracts the anxiolytic response to midazolam on the elevated plus-maze Trial 2 in rats. Behav Brain Res 2005; 162 (1): 99-107. [DOI:10.1016/j.bbr.2005.03.010]
8. Bertoglio LJ, Joca SR, Guimaraes FS. Further evidence that anxiety and memory are regionally dissociated within the hippocampus. Behav Brain Res 2006; 175 (1): 183-188. [DOI:10.1016/j.bbr.2006.08.021]
9. Bodnar RJ. Endogenous opiates and behavior. Peptides 2021; 141: 170547. [DOI:10.1016/j.peptides.2021.170547]
10. Bourin M. Animal models for screening anxiolytic-like drugs: a perspective. Dialogues Clin Neurosci 2015; 17 (3): 295–303. [DOI:10.31887/DCNS.2015.17.3/mbourin]
11. Bush DEA, Caparosa EM, Gekker A, Ledoux J. Beta-adrenergic receptors in the lateral nucleus of the amygdala contribute to the acquisition but not the consolidation of auditory fear conditioning. Front Behav Neurosci 2010; 4: 154. [DOI:10.3389/fnbeh.2010.00154]
12. Carlson ES, Hunker AC, Sandberg SG, Locke TM, Geller GM, Schindler AG, et al. Catecholaminergic innervation of the lateral nucleus of the cerebellum modulates cognitive behaviors. J Neurosci 2021; 41 (15): 3512-3530. [DOI:10.1523/JNEUROSCI.2406-20.2021]
13. Carobrez AP, Bertoglio LJ. Ethological and temporal analyses of anxiety-like behavior: the elevated plus-maze model 20 years on. Neurosci Biobehav Rev 2005; 29 (8): 1193-205. [DOI:10.1016/j.neubiorev.2005.04.017]
14. Chabot-Doré AJ, Schuster DJ, Stone LS, Wilcox GL. Analgesic synergy between opioid and α2 –adrenoceptors. Br J Pharmacol 2015; 172 (2): 388-402. [DOI:10.1111/bph.12695]
15. Cheng YJ, Lin CH, Lane HY. Involvement of cholinergic, adrenergic, and glutamatergic network modulation with cognitive dysfunction in Alzheimer’s Disease. Int J Mol Sci 2021; 22 (5), 2283. [DOI:10.3390/ijms22052283]
16. Clark KL, Noudoost B. The role of prefrontal catecholamines in attention and working memory. Front Neural Circuits 2014; 8: 33. [DOI:10.3389/fncir.2014.00033]
17. Farahmandfar M, Kadivar M, Naghdi N. Possible interaction of hippocampal nitric oxide and calcium/calmodulin-dependent protein kinase II on reversal of spatial memory impairment induced by morphine. Eur J Pharmacol 2015; 751: 99-111. [DOI:10.1016/j.ejphar.2015.01.042]
18. Farahmandfar M, Karimian SM, Zarrindast MR, Kadivar M, Afrouzi H, Naghdi N. Morphine sensitization increases the extracellular level of glutamate in CA1 of rat hippocampus via μ-opioid receptor. Neurosci Lett 2011; 494 (2): 130-4. [DOI:10.1016/j.neulet.2011.02.074]
19. Feng Y, He X, Yang Y, Chao D, Lazarus LH, Xia Y. Current research on opioid receptor function. Curr Drug Targets 2012; 13: 230-246. [DOI:10.2174/138945012799201612]
20. Gianlorenço ACL, Canto-de-Souza A, Mattioli R. Microinjection of histamine into the cerebellar vermis impairs emotional memory consolidation in mice. Brain Res Bull 2011; 86 (1-2): 134-8. [DOI:10.1016/j.brainresbull.2011.05.014]
21. Hagena H, Hansen N, Manahan-Vaughan D. β-Adrenergic control of hippocampal function: subserving the choreography of synaptic information storage and memory. Cereb Cortex 2016; 26 (4): 1349-64. [DOI:10.1093/cercor/bhv330]
22. Heidari MH, Amini A, Bahrami Z, Shahriari A, Movafag A, Heidari R. Effect of chronic morphine consumption on synaptic plasticity of rat’s hippocampus: a transmission electron microscopy study. Neurol Res Int 2013; 2013: 290414. [DOI:10.1155/2013/290414]
23. Jain A, Mishra A, Shakkarpude J, Lakhani P. Beta endorphins: The natural opioids. Int J Chem Stud 2019; 7 (3): 323-332. https://www.researchgate.net/publication/343850641
24. Karunanithi S, Lavidis NA. Effect of chronic morphine treatment on alpha (2)-adrenoceptor mediated autoinhibition of transmitter release from sympathetic varicosities of the mouse vas deferens. Br J Pharmacol 2001; 132 (2): 403–410. [DOI:10.1038/sj.bjp.0703842]
25. Khalifeh S, Khodamoradi M, Hajali V, Ghazvini H, Eliasy L, Kheradmand A, et al. Naloxone ameliorates spatial memory deficits and hyperthermia induced by a neurotoxic methamphetamine regimen in male rats. Galen Med J 2019; 8: e1182. [DOI:10.31661/gmj.v0i0.1182]
26. Kibaly C, Xu C, Cahill CM, Evans CJ, Law PY. Non-nociceptive roles of opioids in the CNS: opioids’ effects on neurogenesis, learning, memory and affect. Nat Rev Neurosci 2019; 20 (1): 5-18. [DOI:10.1038/s41583-018-0092-2]
27. Konen LM, Wright AL, Royle GA, Morris GP, Lau BK, Seow PW, et al. A new mouse line with reduced GluA2 Q/R site RNA editing exhibits loss of dendritic spines, hippocampal CA1-neuron loss, learning and memory impairments and NMDA receptor-independent seizure vulnerability. Mol Brain 2020; 13 (1): 27. [DOI:10.1186/s13041-020-0545-1]
28. Leão AHFF, Medeiros AM, Apolinário GKS, Cabral A, Ribeiro AM, Barbosa FF, et al. Hippocampal-dependent memory in the plus-maze discriminative avoidance task: The role of spatial cues and CA1 activity. Behav Brain Res 2016; 304: 24-33. [DOI:10.1016/j.bbr.2016.02.012]
29. Li YL, Wei S, Liu Q, Gong Q, Zhang QJ, Zheng TG, et al. Mu-opioid receptors in septum mediate the development of behavioural sensitization to a single morphine exposure in male rats. Addict Biol 2021; e13066. [DOI:10.1111/adb.13066]
30. Liu Q, Li Y, Liu Y, Zhao Y, Li X, Zhang Y, et al. A dopamine D1 receptor agonist improved learning and memory in morphine-treated rats. Neurol Res 2018; 40 (12): 1080-1087. [DOI:10.1080/01616412.2018.1519946]
31. McGaugh JL. The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annu Rev Neurosci 2004; 27: 1-28. [DOI:10.1146/annurev.neuro.27.070203.144157]
32. Mello-Carpes PB, de Vargas LDS, Gayer MC, Roehrs R, Izquierdo I. Hippocampal noradrenergic activation is necessary for object recognition memory consolidation and can promote BDNF increase and memory persistence. Neurobiol Learn Mem 2016; 127: 84-92. [DOI:10.1016/j.nlm.2015.11.014]
33. Michel MC, Michel-Reher MB, Hein P. A systematic review of inverse agonism at adrenoceptor subtypes. Cells 2020; 9 (9): 1923. [DOI:10.3390/cells9091923]
34. Miladi-Gorji H, Rashidy-Pour A, Fathollahi Y, Semnanian S, Jadidi M. Effects of voluntary exercise on hippocampal long-term potentiation in morphine-dependent rats. Neuroscience 2014; 256: 83-90. [DOI:10.1016/j.neuroscience.2013.09.056]
35. Millan MJ. The neurobiology and control of anxious states. Prog Neurobiol 2003; 70 (2): 83-244. [DOI:10.1016/s0301-0082(03)00087-x]
36. Montes GC, da Silva BNM, Rezende B, Sudo RT, Ferreira VF, da Silva FDC, et al. The hypnotic, anxiolytic, and antinociceptive profile of a novel µ-opioid agonist. Molecules 2017; 22 (5): 800. [DOI:10.3390/molecules22050800]
37. Murchison CF, Zhang XY, Zhang WP, Ouyang M, Lee A, Thomas SA. A distinct role for norepinephrine in memory retrieval. Cell 2004; 117 (1): 131-43. [DOI:10.1016/s0092-8674(04)00259-4]
38. Nguyen PV, Connor SA. Noradrenergic regulation of hippocampus-dependent memory. Cent Nerv Syst Agents Med Chem 2019; 19 (3): 187-196. [DOI:10.2174/1871524919666190719163632]
39. Paxinos, G., Watson, C., 2007. The Rat Brain in Stereotaxic Coordinates (6rd ed.). Academic Press.London.UK.
40. Peng SY, Li B, Xi K, Wang JJ, Zhu JN. Presynaptic α2-adrenoceptor modulates glutamatergic synaptic transmission in rat nucleus accumbens in vitro. Neurosci Lett 2018; 665: 117-122. [DOI:10.1016/j.neulet.2017.11.060]
41. Porto GP, Milanesi LH, Rubin MA, Mello CF. Effect of morphine on the persistence of long-term memory in rats. Psychopharmacology (Berl) 2015; 232 (10): 1747-53. [DOI:10.1007/s00213-014-3811-z]
42. Pytka K, Podkowa K, Rapacz A, Podkowa A, Żmudzka E, Olczyk A, et al. The role of serotonergic, adrenergic and dopaminergic receptors in antidepressant-like effect. Pharmacol Rep 2015; 68 (2): 263-74. [DOI:10.1016/j.pharep.2015.08.007]
43. Reiss D, Maduna T, Maurin H, Audouard E, Gaveriaux-Ruff C. Mu opioid receptor in microglia contributes to morphine analgesic tolerance, hyperalgesia, and withdrawal in mice. J Neurosci Res 2020; 00: 1-17. [DOI:10.1002/jnr.24626]
44. Rezayof A, Assadpour S, Alijanpour S. Morphine-induced anxiolytic-like effect in morphine-sensitized mice: involvement of ventral hippocampal nicotinic acetylcholine receptors. Pharmacol Biochem Behav 2013; 103 (3): 460-6. [DOI:10.1016/j.pbb.2012.10.003]
45. Roozendaal B, Hermans EJ. Norepinephrine effects on the encoding and consolidation of emotional memory: improving synergy between animal and human studies. Curr Opin Behav Sci 2017; 14: 115-122. [DOI:10.1016/j.cobeha.2017.02.001]
46. Salmanzadeh F, Fathollahi Y, Semnanian S, Shafizadeh M. Dependence on morphine impairs the induction of long-term potentiation in the CA1 region of rat hippocampal slices. Brain Res 2003; 965 (1-2): 108-13. [DOI:10.1016/s0006-8993(02)04144-6]
47. Schneider AM, Simson PE, Daimon CM, Mrozewski J, Vogt NM, Keefe J, Kirby LG. Stress-dependent opioid and adrenergic modulation of newly retrieved fear memory. Neurobiol Learn Mem 2004; 109: 1-6. [DOI:10.1016/j.nlm.2013.11.013]
48. Shi MM, Fan KM, Qiao YN, Xu JH, Qiu LJ, Li X, et al. Hippocampal µ-opioid receptors on GABAergic neurons mediate stress-induced impairment of memory retrieval. Mol Psychiatry 2020; 25 (5): 977-992. [DOI:10.1038/s41380-019-0435-z]
49. Shin IC, Kim HC, Swanson J, Hong JT, Oh KW. Anxiolytic effects of acute morphine can be modulated by nitric oxide systems. Pharmacology 2003; 68: 183-189. [DOI:10.1159/000070457]
50. Sierra-Fonseca JA, Parise LF, Flores-Ramirez FJ, Robles EH, Garcia-Carachure I, Iñiguez SD. Dorsal hippocampus erk2 signaling mediates anxiolytic-related behavior in male rats. Chronic stress 2019; 3: 1-7. [DOI:10.1177/2470547019897030]
51. Śmiałowska M, Zięba B, Domin H. A role of noradrenergic receptors in anxiolytic-like effect of high CRF in the rat frontal cortex. Neuropeptides 2021; 88: 102162. [DOI:10.1016/j.npep.2021.102162]
52. Stemmelin J, Cohen C, Terranova JP, Lopez-Grancha M, Pichat P, Bergis O, et al. Stimulation of the beta3-adrenoceptor as a novel treatment strategy for anxiety and depressive disorders. Neuropsychopharmacology 2008; 33: 574-587. [DOI:10.1038/sj.npp.1301424]
53. Stern CA, Do Monte FH, Gazarini L, Carobrez AP, Bertoglio LJ. Activity in prelimbic cortex is required for adjusting the anxiety response level during the elevated plus-maze retest. Neuroscience 2010; 170 (1): 214-22. [DOI:10.1016/j.neuroscience.2010.06.080]
54. Tang L, Pruitt PJ, Yu Q, Homayouni R, Daugherty AM, Damoiseaux JS, et al. Differential functional connectivity in anterior and posterior hippocampus supporting the development of memory formation. Front Hum Neurosci 2020; 14: 204. [DOI:10.3389/fnhum.2020.00204]
55. Torkaman-Boutorabi A, Sheidadoust H, Hashemi-Hezaveh SM, Zarrindast MR. Influence of morphine on medial prefrontal cortex alpha2 adrenergic system in passive avoidance learning in rats. Pharmacol Biochem Behav 2015; 133: 92-8. [DOI:10.1016/j.pbb.2015.03.018]
56. Uematsu A, Kitamura A, Iwatsuki K, Uneyama H, Tsurugizawa T. Correlation between activation of the prelimbic cortex, basolateral amygdala, and agranular insular cortex during taste memory formation. Cereb Cortex 2015; 25 (9): 2719–2728. [DOI:10.1093/cercor/bhu069]
57. Uskur T, Barlas MA, Akkan AG, Shahzadi A, Uzbay T. Dexmedetomidine induces conditioned place preference in rats: Involvement of opioid receptors. Behav Brain Res 2016; 296: 163-168. [DOI:10.1016/j.bbr.2015.09.017]
58. Valizadegan F, Oryan S, Nasehi M, Zarrindast MR. Interaction between morphine and noradrenergic system of basolateral amygdala on anxiety and memory in the elevated plus-maze test based on a test-retest paradigm. Arch Iran Med 2013; 16 (5): 281-287.
59. Vargas KM, Da Cunha C, Andreatini R. Amphetamine and pentylenetetrazole given post-trial 1 enhance one-trial tolerance to the anxiolytic effect of diazepam in the elevated plus-maze in mice. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30 (8): 1394-402. [DOI:10.1016/j.pnpbp.2006.05.004]
60. Wu Z, Wang T, Li L, Hui Y, Zhang Q, Yuan H. Activation and blockade of α2-adrenoceptors in the prelimbic cortex regulate anxiety-like behaviors in hemiparkinsonian rats. Biochem Biophys Res Commun 2019; 519 (4): 697-704. [DOI:10.1016/j.bbrc.2019.09.038]
61. Zhang G, Wu X, Zhang YM, Liu H, Jiang Q, Pang G, et al. Activation of serotonin 5-HT (2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in morphine-dependent mice. Neuropharmacology 2016; 101: 246-54. [DOI:10.1016/j.neuropharm.2015.09.031]
62. Zhang J, He J, Chen YM, Wang JH, Ma YY. Morphine and propranolol co-administration impair consolidation of Y-maze spatial recognition memory. Brain Res 2008; 1230: 150-7. [DOI:10.1016/j.brainres.2008.06.061]
63. Zhong F, Liu L, Wei JL, Hu ZL, Li L, Wang S, et al. Brain-Derived Neurotrophic Factor Precursor in the Hippocampus Regulates Both Depressive and Anxiety-Like Behaviors in Rats. Front Psychiatry 2019; 9: 776. [DOI:10.3389/fpsyt.2018.00776]

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