EFFECTS OF AGMATINE ON ACOUSTIC STARTLE REFLEX AND AUDITORY SYSTEM IN RATS
DOI:
https://doi.org/10.21776/ub.mnj.2021.007.02.1Keywords:
Neurootology, Neuropharmacology, NeuropathologyAbstract
Background: A polyamine, agmatine, has been proposed as a new neurotransmitter in the brain.
Objective: The aim of this study was to evaluate the effects of acute and chronic agmatine treatment on the rat auditory system.
Methods: Male Wistar albino rats weighing between 280-330 grams were used. Animals were divided into four groups (n= 8 for each group). Acute and chronic agmatine (160 mg/kg) was administered to rats. Prepulse inhibition (PPI) of the acoustic startle reflex (ASR), distortion product otoacoustic emissions (DPOAEs), auditory brainstem responses (ABR) were evaluated in all groups.
Results: Both acute and chronic agmatine treatments also significantly disrupted PPI. Chronic but not acute treatment with agmatine produced some DPOAE and ABR changes in rats.
Conclusion: Our results suggested that chronic agmatine treatment for seven days resulted in some significant negative changes in cochlear function. Because the PPI of the ASR is also used as an indicator for psychoses, such as schizophrenia, in human and experimental animal studies, our findings also imply that the DPOAE and ABR tests may also be considered in the diagnosis and follow-up of patients with psychoses.
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Uzbay T. A new target for diagnosis and treatment of CNS disorders: Agmatinergic system. Curr Med Chem; 2012. 19:5116-5121. DOI: 10.2174/092986712803530601
Uzbay T, Kayir H, Goktalay G, Yildirim M. Agmatine disrupts prepulse inhibition of acoustic startle reflex in rats. J Psychopharmacol; 2010. 24:923-929.
DOI: 10.1177/0269881109102533
Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR. Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: A decade in review. Psychopharmacology; 2001. 156:117-154.
DOI: 10.1007/s002130100811
Braff DL, Swerdlow NR, Geyer MA. Symptom correlates of prepulse inhibition deficits in male schizophrenic patients. Am J Psychiatry; 1999. 156:596-602. DOI: 10.1176/ajp.156.4.596
Uzbay T, Goktalay G, Kayir H, et al. Increased plasma agmatine levels in patients with schizophrenia. J Psychiatr Res; 2013. 47:1054-1060.
DOI: 10.1016/j.jpsychires.2013.04.004
Liu P, Jing Y, Collie ND, Dean B, Bilkey DK, Zhang H. Altered brain arginine metabolism in schizophrenia. Transl Psychiatry; 2016. 6:e871. DOI: 10.1038/tp.2016.144
Ramani D, De Bandt JP, Cynober L. Aliphatic polyamines in physiology and diseases. Clin Nutr; 2014. 33:14-22. DOI: 10.1016/j.clnu.2013.09.019
Fiori LM, Turecki GT. Implication of the polyamine system in mental disorders. J Psychiatry Neurosci; 2008. 33:102-110. Avalaible from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265312/
Geyer MA, Swerdlow NR. Measurement of startle response, prepulse inhibition, and habituation. CurrProtNeurosci; 2001. Chapter 8, Unit 8.7.
DOI: https://doi.org/ 10.1002/0471142301.ns0807s03.
Young JS, Fechter LD. Reflex inhibition procedures for animal audiometry: A technique for assessing ototoxicity. J Acoust Soc Am; 1983. 73:1686-1693.
Walter M, Tziridis K, Ahlf S, Schulze H. Context dependent auditory threshold determined by brainstem audiometry and prepulse inhibition in mongolian gerbils. Open J Acoust; 2012;2:34-49.
DOI: 10.4236/oja.2012.21004
David A, Malmberg A, Lewis G, Brandt L, Allebeck P. Are there neurological and sensory risk factors for schizophrenia? Schizophr Res; 1995. 14:247-251. DOI: 10.1016/0920-9964(94)00068-j
Viertio S, Perala J, Saarni S, Koskinen S, Suvisaari J. Hearing loss in persons with psychotic disorder--findings from a population-based survey. Schizophr Res; 2014. 159: 309-311. DOI: 10.1016/j.schres.2014.08.016
Braff DL, Geyer MA. Sensorimotor gating and schizophrenia: Human and animal model studies. Arch Gen Psychiatry; 1990. 47:181-188.
DOI: 10.1001/archpsyc.1990.01810140081011
Abeloff MD, Rosen ST, Luk GD, Baylin SB, Zeltzman M, Sjoerdsma A. Phase II trials of alpha-difluoromethylornithine, an inhibitor of polyamine synthesis, in advanced small cell lung cancer and colon cancer. Cancer TreatRep; 1986. 70:843-845. Avalaible from:
https://europepmc.org/article/med/3013400
Salzer SJ, Mattox DE, Brownell WE. Cochlear damage and increased threshold in alpha-difluoromethylornithine (DFMO) treated guinea pigs. Hear Res; 1990. 46:101-112. DOI: https://doi.org/10.1016/0378-5955(90)90143-D
Nie L, Feng W, Diaz R, Gratton MA, Doyle KJ, Yamoah EN. Functional consequences of polyamine synthesis inhibition by L-alpha-difluoromethylornithine (DFMO): Cellular mechanisms for DFMO-mediated ototoxicity. J Biol Chem; 2005. 280:15097-15102.
DOI: https://doi.org/10.1074/jbc.M409856200
Göktalay G, Kayir H, Ulusoy GK, Uzbay T. Social interaction of rats is related with baseline prepulse inhibition level. Neurosci Lett.; 2014. 582:125-129. DOI: https://doi.org/10.1074/jbc.M409856200
Lang UE, Puls I, Muller DJ, Strutz-Seebohm N, Gallinat J. Molecular mechanisms of schizophrenia. Cell PhysiolBiochem; 2007. 20:687-702.
DOI: 10.1159/000110430
Hallak JE, de Paula AL, Chaves C, Bressan RA, Machado-de-Sousa JP. An Overview on the Search for Schizophrenia Biomarkers. CNS Neurol Disord Drug Targets; 2015. 14:996-1000.
Richardson-Andrews RC. A central role for the polyamines in the aetiology of schizophrenia. Med Hypotheses; 1983. 11:157-166.
DOI: https://doi.org/10.1016/0306-9877(83)90059-2
Ramchand CN, Das I, Gliddon A, Hirsch SR. Role of polyamines in the membrane pathology of schizophrenia. A study using fibroblasts from schizophrenic patients and normal controls. Schizophr Res; 1994. 13:249-253. DOI: 10.1016/0920-9964(94)90049-3
Tsai G, Coyle JT. Glutamatergic mechanisms in schizophrenia. Annu Rev Pharmacol Toxicol; 2002. 42:165-179.
DOI: 10.1146/annurev.pharmtox.42.082701.160735
Lindsley CW, Shipe WD, Wolkenberg SE, et al. Progress towards validating the NMDA receptor hypofunction hypothesis of schizophrenia. Curr Top Med Chem; 2006. 6:771-785.
DOI: 10.2174/156802606777057599
Yang XC, Reis DJ. Agmatine selectively blocks the N-methyl-D-aspartate subclass of glutamate receptor channels in rat hippocampal neurons. J Pharmacol Exp Ther; 1999. 288:544-549. Avalaible from: https://pubmed.ncbi.nlm.nih.gov/9918557/
Naguib MB, Hunter RE, Henley CM. Cochlear polyamines: Markers of otitis media-induced cochlear damage. Laryngoscope; 1994. 0104(8 Pt 1):1003-1007. DOI: 10.1288/00005537-199408000-00015
Brock M, Henley CM. Postnatal changes in cochlear polyamine metabolism in the rat. Hear Res; 1994. 72:37-43. DOI: 10.1016/0378-5955(94)90203-8
Puel JL. Chemical synaptic transmission in the cochlea. Prog Neurobiol; 1995. 47:449-476.
DOI: 10.1016/0301-0082(95)00028-3
Usami S, Matsubara A, Fujita S, Shinkawa H, Hayashi M. NMDA (NMDAR1) and AMPA-type (GluR2/3) receptor subunits are expressed in the inner ear. Neuroreport; 1995. 6:1161-1164.
Safieddine S, Eybalin M. Co-expression of NMDA and AMPA/kainate receptor mRNAs in cochlear neurones. Neuroreport; 1992. 3:1145-1148.
DOI: 10.1097/00001756-199212000-00029
Basile AS, Huang JM, Xie C, Webster D, Berlin C, Skolnick P. N-methyl-D-aspartate antagonists limit aminoglycoside antibiotic-induced hearing loss. Nat Med; 1996. 2:1338-43. DOI: 10.1038/nm1296-1338
Brechtelsbauer PB, Nuttall AL, Miller JM. Basal nitric oxide production in regulation of cochlear blood flow. Hear Res.1994;77:38-42. DOI: 10.1016/0378-5955(94)90251-8
Budni J, Gadotti VM, Kaster MP, Santos AR, Rodrigues AL. Role of different types of potassium channels in the antidepressant-like effect of agmatine in the mouse forced swimming test. Eur J Pharmacol; 2007. 575:87-93. DOI: 10.1016/j.ejphar.2007.08.010
Kantrowitz JT, Epstein ML, Beggel O, et al. Neurophysiological mechanisms of cortical plasticity impairments in schizophrenia and modulation by the NMDA receptor agonist D-serine. Brain; 2016. 139(12):3281-3295. DOI: 10.1093/brain/aww262
Quednow BB, Frommann I, Berning J, Kuhn KU, Maier W, Wagner M. Impaired sensorimotor gating of the acoustic startle response in the prodrome of schizophrenia. Biol Psychiatry; 2008. 64:766-773. DOI: 10.1093/brain/aww262
Hammer TB, Oranje B, Fagerlund B, Bro H, Glenthoj BY. Stability of prepulse inhibition and habituation of the startle reflex in schizophrenia: A 6-year follow-up study of initially antipsychotic-naive, first-episode
schizophrenia patients. Int J Neuropsychopharmacol; 2011. 14:913-925.
DOI: 10.1017/S1461145711000034
Ludewig K, Ludewig S, Seitz A, Obrist M, Geyer MA, Vollenweider FX. The acoustic startle reflex and its modulation: Effects of age and gender in humans. Biol Psychol; 2003. 63:311-323. DOI: 10.1016/s0301-0511(03)00074-7
Li J, Wu C, Zheng Y, et al. Schizophrenia affects speech-induced functional connectivity of the superior temporal gyrus under cocktail-party listening conditions. Neuroscience; 2017. 359:248-257.
DOI: 10.1016/j.neuroscience.2017.06.043
Zheng Y, Wu C, Li J, et al. Brain substrates of perceived spatial separation between speech sources under simulated reverberant listening conditions in schizophrenia. Psychol Med; 2016. 46:477-491.
DOI: https://doi.org/10.1017/S0033291715001828
Henley C, Igarashi M. Polyamines in the lateral vestibular nuclei of the Squirrel Monkey and their potential role in vestibular compensation. Acta Otolaryngol; 1993. 113:235-238.
DOI: 10.3109/00016489309135799
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