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Investigating the role of imidazoline-2 receptors in in vivo model of morphine dependence

Year 2011, Volume: 1 Issue: 2, 88 - 95, 31.01.2014

Abstract

Objective: The present study was designed to investigate the effects of imidazoline (I) receptors, especially I2 subtype, in in vivo morphine dependence.
Methods: In vivo study was done by observing behavioural signs of morphine withdrawal in morphine dependent rats after treatment with selective I2 receptor agonist 2-BFI and selective I2 receptor antagonist BU224. Two morphine pellets, each containing 75 mg of morphine base, were implanted subcutaneously in the scapular area of Sprague-Dawley rats. Seventy-two hours after morphine implantation, 2-BFI (3, 5, 10 mg/kg), BU224 (3, 5, 10 mg/kg) or saline was injected to rats intraperitoneally (i.p.). Thirty minutes later, a morphine withdrawal syndrome was precipitated by naloxone (2 mg/kg). Just after the naloxone injection, morphine withdrawal signs such as jumping, wet dog shakes, teeth chattering, defecation, diarrhea, tremor and ptosis were observed and evaluated for 15 min.
Results: Both 2-BFI and BU224, which are administered before naloxone-precipitated withdrawal syndrome, attenuated withdrawal symptoms dose dependently. Low doses of 2-BFI (3 mg/kg) on jumping and low dose of BU224 were found ineffective on wet dog shakes and weight lost.
Conclusion: The present study showed that both 2-BFI and BU224 attenuated the intensity of many signs of the naloxoneprecipitated morphine withdrawal syndrome in rats. Based on these findings, it is thought that imidazoline system may play an important role in morphine dependence and morphine withdrawal, via it’s receptors or/and other mechanisms.

Key words: 2-BFI, BU224, imidazoline-2 receptors, dependence, morphine

References

  • Bodnar RJ. (2008). Endogenous opiates and behaviour: Peptides. 2007; 29 (12): 2292-2375.
  • Ozawa T, Nakagawa T, Shige K, Minami M, Satoh M. Changes in the expression of glial glutamate transporters in the rat brain accompanied with morphine dependence and naloxone-precipitated withdrawal. Brain Res. 2001; 905 (1-2): 254-258.
  • Han MH, Bolanos CA, Green TA, Olson VG, Neve RL, Liu RJ, Aghajanian GK, Nestler EJ. Role of cAMP response element-binding protein in the rat locus ceoruleus: Regulation of neuronal activity and opiate withdrawal behaviours. J Neurosci. 2006; 26 (17): 4624-4629.
  • Ruiz-Durantez E, Torrecilla M, Pineda J, Ugedo L. Attenuation of acute and chronic effects of morphine by the imidazoline receptor ligand 2-(2-benzofuranyl)-2-imidazoline in rat locus ceoruleus neurons. Br J Pharmacol. 2003; 138 (3): 494-500.
  • Bousquet P. Imidazoline Receptors: From Basic Concepts to Recent Developments. J Cardiovasc Pharmacol. 1995; 26 (2): 1-6.
  • Bousquet P. Imidazoline receptors. Neurochem. Int. 1997; 30 (1): 3-7.
  • Bour S, Iglesias-Osma MC, Marti L, Duro P, Garcia-Barrado MJ, Valet P, Moratinos J, Carpene C. (2006). The imidazoline I2-site ligands BU 224 ve 2-BFI inhibit MAO-A and MAO-B activities, hydrogen peroxide production, and lipolysis in rodent and human adipocytes. Eur J Pharmacol. 1997; 552 (1-3): 20-30.
  • Head GA, Mayorov DN. Imidazoline receptors, novel agents and therapeutic potential. Cardiovas Hematol Agents Med Chem. 2006; 4 (1): 17-32.
  • Hudson AL, Gough R, Tyacke R, Lione L, Lalies M, Lewis J, Husbands S, Knight P, Murray F, Hutson P, Nutt DJ. Novel selective compounds for the investigation of imidazoline receptors. Ann N Y Acad Sci. 1999; 881: 81-91.
  • Robinson ES, Tyacke RJ, Nutt DJ, Hudson AL. Distribution of [3H] BU224, a selective imidazoline I2 binding site ligand, in rat brain. Eur J Pharmacol. 2002; 450 (1): 55-60.
  • Hudson AL, Tyacke RJ, Lalies MD, Davies N, Finn DP, Martı O, Robinson E, Husbands S, Minchin MCW, Kimura A, Nutt DJ. Novel ligands for the investigation of imidazoline receptors and their binding proteins. Ann N Y Acad Sci. 2003; 1009: 302-308.
  • Garcia-Sevilla JA, Escriba PV, Guimon J. Imidazoline receptors and human brain disorders. Ann N Y Acad Sci. 1999; 881: 392-409.
  • Reynolds GP, Boulton RM, Pearson SJ, Hudson AL, Nutt DJ. Imidazoline binding sites in Huntington’s and Parkinson’s disease putamen. Eur J Pharmacol. 1996; 301 (1-3): 19-21.
  • Ruiz J, Martin I, Callado LF, Meana JJ, Barturen F, Garcia-Sevilla JA. Non-adrenoreceptor [3H]idazoxan binding sites (I2-imidazoline sites) are increased in postmortem brain from patients with Alzheimer’s disease. Neurosci Lett. 1993; 160 (1): 109-112.
  • Sastre M, Ventayol P, Garcia-Sevilla JA. Decreased density of I2-imidazoline receptors in the postmortem brains of heroin addicts. Neuroreport. 1996; 7 (2): 509-512.
  • Lione LA, Nutt DJ, Hudson AL. Characterisation and localisation of [3H]2-(2-benzofuranyl)-2-imidazoline binding in rat brain: A selective ligand for imidazoline I2 receptors. Eur J Pharmacol. 1998; 353 (1): 123-35.
  • Ugedo L, Pineda J, Ruiz-Ortega JA, Martin-Ruiz R. Stimulation of locus coeruleus neurons by non-I1/I2-type imidazoline receptors: an in vivo and in vitro electrophysiological study. Br J Pharmacol. 1998; 125 (8): 1685-1694.
  • Boronat MA, Olmos G, Garcia-Sevilla JA. Attenuation of tolerance to opioid-induced antinociception and protection against morphine- induced decrease of neurofilament proteins by idazoxan and other I2-imidazoline ligands. Br J Pharmacol. 1998; 125 (1): 175-185.
  • Way EL, Loh HH, Shen F. Simultaneous quantitative assesment of morphine tolerance and physical dependence. J Pharmacol Exp Ther. 1969; 167 (1): 1-8.
  • Sanchez-Blazquez P, Boronat MA, Olmos G, Garcia-Sevilla JA, Garzon J. Activation of I2-imidazoline receptors enhances supraspinal analgesia in mice: A model to detect agonist antagonist activities. Br J Pharmacol. 2000; 130 (1): 146-152.
  • Finn DP, Lalies MD, Harbuz MS, Jessop DS, Hudson AL, Nutt DJ. Imidazoline 2 (I2) binding site- and α2-adrenoreceptor-mediated modulation of central noradrenergic and HPA axis function in control rats and chronically stressed rats with adjuvant-induced arthritis. Neuropharmacol. 2002; 42 (7): 958-965.
  • Finn DP, Marti O, Harbuz MS, Valles A, Belda X, Marquez C, Jessop DS, Lalies MD, Armario A, Nutt DJ, Hudson AL. Behavioral, neuroendocrine and neurochemical effects of the imidazoline I2 receptor selective ligand BU224 in naive rats and rats exposed to the stress of the forced swim test. Psychopharmacol. 2003; 167 (2): 195-202.
  • Finn DP, Hudson AL, Kinoshita H, Coventry TL, Jessop DS, Nutt DJ, Harbuz MS. Imidazoline 2 (I2) receptor and alpha2-adrenoreceptor-mediated modulation of hypotalamic-pituitary-adrenal axis activity in control and acute restraint stressed rats. J Psychopharmacol. 2004; 18 (1): 47-53.
  • Diaz A, Mayet S, Dickenson AH. BU-224 produces spinal antinociception as an agonist at imidazoline I2 receptors. Eur J Pharmacol. 1997; 333 (1): 9-15.
  • Smith KL, Roche M, Jessop DS, Finn DP. The effects of synthetic and endogenous imidazoline binding site ligands on neuronal activity in discrete brain regions of naive and restraint-stressed rats. Eur Neuropsychopharmocol. 2009; 19 (5): 371-380.
  • Adams ML, Kalicki JM., Meyer ER., Cicero TJ. Inhibition of the morphine withdrawal syndrome by a nitric oxide synthase inhibitor, NG-nitro-L- arginine methyl ester. Life Sci. 1993; 52 (22): 245-249.
  • Cappendijk SL, De Vries R, Dzoljic MR. Inhibitory effect of nitric oxide (NO) synthase inhibitors on naloxone-precipitated withdrawal syndrome in morphine-dependent mice. Neurosci Lett. 1993; 162 (1-2): 97-100.
  • Kimes AS, Vaupel DB, London ED. Attenuation of some signs of opioid withdrawal by inhibitors of nitric oxidesynthase. Psychopharmacol. 1993; 112(4): 521-524.
  • Vaupel DB, Kimes AS, London ED. Nitric oxide synthase inhibitors. Preclinical studies of potential use for treatment of opioid withdrawal. Neuropsychopharmacology. 1995; 13(4):315-22.
  • Walker JR, Ahmed SH, Gracy KN, Koob GF. Microinjections of an opiate receptor antagonist into the bed nucleus of the stria terminalis suppress heroin self-administration in dependent rats. Brain Res. 2000; 854 (1-2): 85-92.
  • Hedou G, Feldon J, Heidbreder CA. Effects of cocaine on dopamine in subregions of the rat prefrontal cortex and their efferents to subterritories of the nucleus accumbens. Eur J Pharmacol. 1999; 372 (2):143-155.
  • Ruiz-Durantez E, Ruiz-Ortega JA, Pineda J, Ugedo L. Effect of agmatine on locus ceoruleus neuron activity: possible involvement of nitric oxide. Br J Pharmacol. 2002; 135 (5): 1152-8.
  • Morgan AD, Campbell UC, Fons RD, Carroll ME. Effects of agmatine on the escalation of intravenous cocaine and fentanyl self-administration in rats. Pharmacol Biochem Behav. 2002; 72 (4): 873-880.
  • Arıcıoğlu-Kartal F, Uzbay IT. Inhibitory effect of agmatine on naloxone- precipatated abstinence syndrome. Life Sci. 1997; 61(18): 1775-1881.
  • Arıcıoğlu-Kartal F, Regunathan S. Effect of chronic morphine treatment on the biosynthesis of agmatine in rat brain and other tissues. Life Sci. 2002; 71(14): 1695-1701.
  • Arıcıoğlu F, Means A, Regunathan S. Effect of agmatine on the development of morphine dependence in rats: potential role of cAMP system. Eur J Pharmacol. 2004; 504 (3): 191-197.
  • Arıcıoğlu F, Paul IA, Regunathan S. Agmatine reduces only peripheral- related behavioral signs, not the central signs, of morphine withdrawal in nNOS deficient transgenic mice. Neurosci. Lett. 2004; 9; 354 (2):153-157.
  • Wei XL, Su RB, Wu N, Lu XQ, Zheng JQ, Li J. Agmatine inhibits morphine-induced locomotion sensitization and morphine- induced changes in striatal dopamine and metabolites in rats. Eur Neuropsychopharmacol. 2007; 17 (12): 790-799.
  • Yananlı H, Gören MZ, Berkman K, Arıcıoğlu F. Effect of agmatine on brain L- citrulline production during morphine withdrawal in rats: A microdialysis study in nucleus accumbens. Brain Res. 2007; 1132 (1): 51-58.
  • Arıcıoğlu-Kartal F, Erçil E, Dülger G. Agmatine inhibits naloxone- induced contractions in morphine-dependent guinea pig ileum. Ann N Y Acad Sci. 2003; 1009: 147-151.
  • Atcheson R, Rowbotham DJ, Lambert DG. Fentanyle inhibits the release of noradrenaline from SH-SY5Y human neuroblastoma cells. Br J Anaesth. 1994; 72 (1): 98-103.
  • Sahraei H, Ghazzaghi H, Zarrindast M, Ghoshooni H. The role of alpha-adrenoceptor mechanism(s) in morphine-induced conditioned place preference in female mice. Pharmacol Biochem Behav. 2004; 78 (1):135-41.
  • Kosten TA. Clonidine attenuates conditioned aversion produced by naloxene-precipitated opiate withdrawal. Eur J Pharmacol. 1994; 254 (1-2): 59-63.

İmidazolin-2 reseptörlerinin rolünün in vivo morfin bağımlılığı modelinde araştırılması

Year 2011, Volume: 1 Issue: 2, 88 - 95, 31.01.2014

Abstract

Amaç: Bu çalışma son yıllarda tanımlanan imidazolin (I) reseptörlerinin özellikle I2 alt tipine seçici olarak bağlanan maddelerden yararlanarak söz konusu reseptörlerin morfin bağımlılığındaki etkisini araştırmak üzere planlanmıştır.
Yöntem: I2 reseptörlerinin agonisti olan 2-BFI ve antagonisti olan BU224 in vivo bağımlılık modellerinde kullanılmıştır. İn vivo bağımlılık Sprague-Dawley sıçanlara ciltaltı morfin peleti (toplam 150 mg) yerleştirilerek oluşturulmuştur. İmplantasyondan 72 saat sonra intraperitoneal (i.p.) olarak 2-BFI (3, 5 veya 10 mg/ kg) veya BU224 (3, 5 veya 10 mg/kg) uygulamasından 30 dakika sonra nalokson (2 mg/kg) enjekte edilerek değerlendirilmiştir. Nalokson uygulamasının hemen ardından sıçanlar 15 dakika boyunca gözlenerek sıçrama, ıslak köpek titremesi, karın germe, defekasyon, pitozis, diş gıcırdatma, diyare, tremor gibi morfin yoksunluğu belirtileri kaydedilmiştir.
Bulgular: Hem 2-BFI hem de BU224 naloksonla yoksunluk sendromu oluşturmadan önce uygulandığında yoksunluk semptomlarını doza bağımlı bir biçimde baskılanmıştır. 2-BFI’nın en düşük dozu (3 mg/kg) sıçramada ve BU224’ün en düşük dozu (3 mg/kg) ıslak köpek titremesi ve kilo kaybında etkisiz bulunmuştur.
Sonuç: Hem 2-BFI hem de BU224’ün yoksunluk semptomlarını baskıladığı gösterilmiştir. Bu çalışmanın sonuçları I sisteminin belki kısmen reseptörleri aracılığıyla belki de farklı mekanizmaları kullanarak morfin bağımlılığı ve/veya yoksunluğunda önemli rolü olduğunu düşündürmektedir.

Anahtar Kelimeler : 2-BFI, BU224, imidazolin-2 reseptörleri,bağımlılık, morfin

References

  • Bodnar RJ. (2008). Endogenous opiates and behaviour: Peptides. 2007; 29 (12): 2292-2375.
  • Ozawa T, Nakagawa T, Shige K, Minami M, Satoh M. Changes in the expression of glial glutamate transporters in the rat brain accompanied with morphine dependence and naloxone-precipitated withdrawal. Brain Res. 2001; 905 (1-2): 254-258.
  • Han MH, Bolanos CA, Green TA, Olson VG, Neve RL, Liu RJ, Aghajanian GK, Nestler EJ. Role of cAMP response element-binding protein in the rat locus ceoruleus: Regulation of neuronal activity and opiate withdrawal behaviours. J Neurosci. 2006; 26 (17): 4624-4629.
  • Ruiz-Durantez E, Torrecilla M, Pineda J, Ugedo L. Attenuation of acute and chronic effects of morphine by the imidazoline receptor ligand 2-(2-benzofuranyl)-2-imidazoline in rat locus ceoruleus neurons. Br J Pharmacol. 2003; 138 (3): 494-500.
  • Bousquet P. Imidazoline Receptors: From Basic Concepts to Recent Developments. J Cardiovasc Pharmacol. 1995; 26 (2): 1-6.
  • Bousquet P. Imidazoline receptors. Neurochem. Int. 1997; 30 (1): 3-7.
  • Bour S, Iglesias-Osma MC, Marti L, Duro P, Garcia-Barrado MJ, Valet P, Moratinos J, Carpene C. (2006). The imidazoline I2-site ligands BU 224 ve 2-BFI inhibit MAO-A and MAO-B activities, hydrogen peroxide production, and lipolysis in rodent and human adipocytes. Eur J Pharmacol. 1997; 552 (1-3): 20-30.
  • Head GA, Mayorov DN. Imidazoline receptors, novel agents and therapeutic potential. Cardiovas Hematol Agents Med Chem. 2006; 4 (1): 17-32.
  • Hudson AL, Gough R, Tyacke R, Lione L, Lalies M, Lewis J, Husbands S, Knight P, Murray F, Hutson P, Nutt DJ. Novel selective compounds for the investigation of imidazoline receptors. Ann N Y Acad Sci. 1999; 881: 81-91.
  • Robinson ES, Tyacke RJ, Nutt DJ, Hudson AL. Distribution of [3H] BU224, a selective imidazoline I2 binding site ligand, in rat brain. Eur J Pharmacol. 2002; 450 (1): 55-60.
  • Hudson AL, Tyacke RJ, Lalies MD, Davies N, Finn DP, Martı O, Robinson E, Husbands S, Minchin MCW, Kimura A, Nutt DJ. Novel ligands for the investigation of imidazoline receptors and their binding proteins. Ann N Y Acad Sci. 2003; 1009: 302-308.
  • Garcia-Sevilla JA, Escriba PV, Guimon J. Imidazoline receptors and human brain disorders. Ann N Y Acad Sci. 1999; 881: 392-409.
  • Reynolds GP, Boulton RM, Pearson SJ, Hudson AL, Nutt DJ. Imidazoline binding sites in Huntington’s and Parkinson’s disease putamen. Eur J Pharmacol. 1996; 301 (1-3): 19-21.
  • Ruiz J, Martin I, Callado LF, Meana JJ, Barturen F, Garcia-Sevilla JA. Non-adrenoreceptor [3H]idazoxan binding sites (I2-imidazoline sites) are increased in postmortem brain from patients with Alzheimer’s disease. Neurosci Lett. 1993; 160 (1): 109-112.
  • Sastre M, Ventayol P, Garcia-Sevilla JA. Decreased density of I2-imidazoline receptors in the postmortem brains of heroin addicts. Neuroreport. 1996; 7 (2): 509-512.
  • Lione LA, Nutt DJ, Hudson AL. Characterisation and localisation of [3H]2-(2-benzofuranyl)-2-imidazoline binding in rat brain: A selective ligand for imidazoline I2 receptors. Eur J Pharmacol. 1998; 353 (1): 123-35.
  • Ugedo L, Pineda J, Ruiz-Ortega JA, Martin-Ruiz R. Stimulation of locus coeruleus neurons by non-I1/I2-type imidazoline receptors: an in vivo and in vitro electrophysiological study. Br J Pharmacol. 1998; 125 (8): 1685-1694.
  • Boronat MA, Olmos G, Garcia-Sevilla JA. Attenuation of tolerance to opioid-induced antinociception and protection against morphine- induced decrease of neurofilament proteins by idazoxan and other I2-imidazoline ligands. Br J Pharmacol. 1998; 125 (1): 175-185.
  • Way EL, Loh HH, Shen F. Simultaneous quantitative assesment of morphine tolerance and physical dependence. J Pharmacol Exp Ther. 1969; 167 (1): 1-8.
  • Sanchez-Blazquez P, Boronat MA, Olmos G, Garcia-Sevilla JA, Garzon J. Activation of I2-imidazoline receptors enhances supraspinal analgesia in mice: A model to detect agonist antagonist activities. Br J Pharmacol. 2000; 130 (1): 146-152.
  • Finn DP, Lalies MD, Harbuz MS, Jessop DS, Hudson AL, Nutt DJ. Imidazoline 2 (I2) binding site- and α2-adrenoreceptor-mediated modulation of central noradrenergic and HPA axis function in control rats and chronically stressed rats with adjuvant-induced arthritis. Neuropharmacol. 2002; 42 (7): 958-965.
  • Finn DP, Marti O, Harbuz MS, Valles A, Belda X, Marquez C, Jessop DS, Lalies MD, Armario A, Nutt DJ, Hudson AL. Behavioral, neuroendocrine and neurochemical effects of the imidazoline I2 receptor selective ligand BU224 in naive rats and rats exposed to the stress of the forced swim test. Psychopharmacol. 2003; 167 (2): 195-202.
  • Finn DP, Hudson AL, Kinoshita H, Coventry TL, Jessop DS, Nutt DJ, Harbuz MS. Imidazoline 2 (I2) receptor and alpha2-adrenoreceptor-mediated modulation of hypotalamic-pituitary-adrenal axis activity in control and acute restraint stressed rats. J Psychopharmacol. 2004; 18 (1): 47-53.
  • Diaz A, Mayet S, Dickenson AH. BU-224 produces spinal antinociception as an agonist at imidazoline I2 receptors. Eur J Pharmacol. 1997; 333 (1): 9-15.
  • Smith KL, Roche M, Jessop DS, Finn DP. The effects of synthetic and endogenous imidazoline binding site ligands on neuronal activity in discrete brain regions of naive and restraint-stressed rats. Eur Neuropsychopharmocol. 2009; 19 (5): 371-380.
  • Adams ML, Kalicki JM., Meyer ER., Cicero TJ. Inhibition of the morphine withdrawal syndrome by a nitric oxide synthase inhibitor, NG-nitro-L- arginine methyl ester. Life Sci. 1993; 52 (22): 245-249.
  • Cappendijk SL, De Vries R, Dzoljic MR. Inhibitory effect of nitric oxide (NO) synthase inhibitors on naloxone-precipitated withdrawal syndrome in morphine-dependent mice. Neurosci Lett. 1993; 162 (1-2): 97-100.
  • Kimes AS, Vaupel DB, London ED. Attenuation of some signs of opioid withdrawal by inhibitors of nitric oxidesynthase. Psychopharmacol. 1993; 112(4): 521-524.
  • Vaupel DB, Kimes AS, London ED. Nitric oxide synthase inhibitors. Preclinical studies of potential use for treatment of opioid withdrawal. Neuropsychopharmacology. 1995; 13(4):315-22.
  • Walker JR, Ahmed SH, Gracy KN, Koob GF. Microinjections of an opiate receptor antagonist into the bed nucleus of the stria terminalis suppress heroin self-administration in dependent rats. Brain Res. 2000; 854 (1-2): 85-92.
  • Hedou G, Feldon J, Heidbreder CA. Effects of cocaine on dopamine in subregions of the rat prefrontal cortex and their efferents to subterritories of the nucleus accumbens. Eur J Pharmacol. 1999; 372 (2):143-155.
  • Ruiz-Durantez E, Ruiz-Ortega JA, Pineda J, Ugedo L. Effect of agmatine on locus ceoruleus neuron activity: possible involvement of nitric oxide. Br J Pharmacol. 2002; 135 (5): 1152-8.
  • Morgan AD, Campbell UC, Fons RD, Carroll ME. Effects of agmatine on the escalation of intravenous cocaine and fentanyl self-administration in rats. Pharmacol Biochem Behav. 2002; 72 (4): 873-880.
  • Arıcıoğlu-Kartal F, Uzbay IT. Inhibitory effect of agmatine on naloxone- precipatated abstinence syndrome. Life Sci. 1997; 61(18): 1775-1881.
  • Arıcıoğlu-Kartal F, Regunathan S. Effect of chronic morphine treatment on the biosynthesis of agmatine in rat brain and other tissues. Life Sci. 2002; 71(14): 1695-1701.
  • Arıcıoğlu F, Means A, Regunathan S. Effect of agmatine on the development of morphine dependence in rats: potential role of cAMP system. Eur J Pharmacol. 2004; 504 (3): 191-197.
  • Arıcıoğlu F, Paul IA, Regunathan S. Agmatine reduces only peripheral- related behavioral signs, not the central signs, of morphine withdrawal in nNOS deficient transgenic mice. Neurosci. Lett. 2004; 9; 354 (2):153-157.
  • Wei XL, Su RB, Wu N, Lu XQ, Zheng JQ, Li J. Agmatine inhibits morphine-induced locomotion sensitization and morphine- induced changes in striatal dopamine and metabolites in rats. Eur Neuropsychopharmacol. 2007; 17 (12): 790-799.
  • Yananlı H, Gören MZ, Berkman K, Arıcıoğlu F. Effect of agmatine on brain L- citrulline production during morphine withdrawal in rats: A microdialysis study in nucleus accumbens. Brain Res. 2007; 1132 (1): 51-58.
  • Arıcıoğlu-Kartal F, Erçil E, Dülger G. Agmatine inhibits naloxone- induced contractions in morphine-dependent guinea pig ileum. Ann N Y Acad Sci. 2003; 1009: 147-151.
  • Atcheson R, Rowbotham DJ, Lambert DG. Fentanyle inhibits the release of noradrenaline from SH-SY5Y human neuroblastoma cells. Br J Anaesth. 1994; 72 (1): 98-103.
  • Sahraei H, Ghazzaghi H, Zarrindast M, Ghoshooni H. The role of alpha-adrenoceptor mechanism(s) in morphine-induced conditioned place preference in female mice. Pharmacol Biochem Behav. 2004; 78 (1):135-41.
  • Kosten TA. Clonidine attenuates conditioned aversion produced by naloxene-precipitated opiate withdrawal. Eur J Pharmacol. 1994; 254 (1-2): 59-63.
There are 43 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Zehra Çetin This is me

Tijen Utkan This is me

Alan Hudson This is me

Feyza Arıcıoğlu

Publication Date January 31, 2014
Submission Date November 2, 2013
Published in Issue Year 2011 Volume: 1 Issue: 2

Cite

APA Çetin, Z., Utkan, T., Hudson, A., Arıcıoğlu, F. (2014). İmidazolin-2 reseptörlerinin rolünün in vivo morfin bağımlılığı modelinde araştırılması. Clinical and Experimental Health Sciences, 1(2), 88-95.
AMA Çetin Z, Utkan T, Hudson A, Arıcıoğlu F. İmidazolin-2 reseptörlerinin rolünün in vivo morfin bağımlılığı modelinde araştırılması. Clinical and Experimental Health Sciences. January 2014;1(2):88-95.
Chicago Çetin, Zehra, Tijen Utkan, Alan Hudson, and Feyza Arıcıoğlu. “İmidazolin-2 reseptörlerinin rolünün in Vivo Morfin bağımlılığı Modelinde araştırılması”. Clinical and Experimental Health Sciences 1, no. 2 (January 2014): 88-95.
EndNote Çetin Z, Utkan T, Hudson A, Arıcıoğlu F (January 1, 2014) İmidazolin-2 reseptörlerinin rolünün in vivo morfin bağımlılığı modelinde araştırılması. Clinical and Experimental Health Sciences 1 2 88–95.
IEEE Z. Çetin, T. Utkan, A. Hudson, and F. Arıcıoğlu, “İmidazolin-2 reseptörlerinin rolünün in vivo morfin bağımlılığı modelinde araştırılması”, Clinical and Experimental Health Sciences, vol. 1, no. 2, pp. 88–95, 2014.
ISNAD Çetin, Zehra et al. “İmidazolin-2 reseptörlerinin rolünün in Vivo Morfin bağımlılığı Modelinde araştırılması”. Clinical and Experimental Health Sciences 1/2 (January 2014), 88-95.
JAMA Çetin Z, Utkan T, Hudson A, Arıcıoğlu F. İmidazolin-2 reseptörlerinin rolünün in vivo morfin bağımlılığı modelinde araştırılması. Clinical and Experimental Health Sciences. 2014;1:88–95.
MLA Çetin, Zehra et al. “İmidazolin-2 reseptörlerinin rolünün in Vivo Morfin bağımlılığı Modelinde araştırılması”. Clinical and Experimental Health Sciences, vol. 1, no. 2, 2014, pp. 88-95.
Vancouver Çetin Z, Utkan T, Hudson A, Arıcıoğlu F. İmidazolin-2 reseptörlerinin rolünün in vivo morfin bağımlılığı modelinde araştırılması. Clinical and Experimental Health Sciences. 2014;1(2):88-95.

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