RSS-Feed abonnieren
DOI: 10.1055/s-0033-1358728
Duloxetine Attenuated Morphine Withdrawal Syndrome in the Rat
Publikationsverlauf
received 17. September 2013
accepted 24. Oktober 2013
Publikationsdatum:
21. November 2013 (online)
Abstract
Background:
Long term exposure to morphine can induce dependence. The exact mechanisms of dependence are not yet fully understood. Many studies have been conducted to find new drugs that can prevent dependence. This study examined the effects of the chronic administration of duloxetine on the morphine withdrawal syndrome in rats.
Methods:
To this end, male Wistar rats (170–220 g) were randomly divided into 5 groups including one saline treated group (non-dependent group) and 4 morphine dependent groups. The experimental groups received additive doses of morphine for 9 days in order to induce dependence according to the following protocol: day 1: 5 mg/kg/12 h, days 2 and 3: 10 mg/kg/12 h, days 4, 5: 15 mg/kg/12 h, days 6 and 7: 20 mg/kg/12 h and days 8 and 9: 25 mg/kg/12 h. On the ninth day, the morning dose of morphine was only injected. It is worth noting that 30 min before the morning dose of morphine, duloxetine (10, 20, and 40 mg/kg) was injected intraperitoneally. In addition, 2 h after the last injection of morphine, the morphine withdrawal was precipitated by naloxone. The withdrawal signs were recorded for 30 min; these signs included jumping, rearing, genital grooming, abdominal writhing, wet dog shaking, and teeth grinding.
Results:
The results of the study revealed that the chronic administration of duloxetine decreased all the withdrawal signs. Besides, it attenuated the total withdrawal scores significantly.
Conclusion:
Results indicate that the regulatory effects on serotonergic and noradrenergic parameters might be associated with the amelioration of the withdrawal symptoms.
-
References
- 1 Riahi E, Mirzaii-Dizgah I, Karimian SM et al. Attenuation of morphine withdrawal signs by a GABAB receptor agonist in the locus coeruleus of rats. Behav Brain Res 2009; 196: 11-14
- 2 Sadeghi M, Sianati S, Anaraki DK et al. Study of morphine-induced dependence in gonadectomized male and female mice. Pharmacol Biochem Behav 2009; 91: 604-609
- 3 Childers SR. Opioid receptor-coupled second messenger systems. Life Sci 1991; 48: 1991-2003
- 4 Nestler EJ, Aghajanian GK. Molecular and cellular basis of addiction. Science 1997; 278: 58-63
- 5 Gold MS. Opiate addiction and the locus coeruleus. The clinical utility of clonidine, naltrexone, methadone, and buprenorphine. Psychiatr Clin North Am 1993; 16: 61-73
- 6 Sastre-Coll A, Esteban S, Garcia-Sevilla JA. Supersensitivity of 5-HT1A autoreceptors and alpha2-adrenoceptors regulating monoamine synthesis in the brain of morphine-dependent rats. Naunyn Schmiedebergs Arch Pharmacol 2002; 365: 210-219
- 7 Maldonado R. Participation of noradrenergic pathways in the expression of opiate withdrawal: biochemical and pharmacological evidence. Neurosci Biobehav Rev 1997; 21: 91-104
- 8 Maldonado R, Stinus L, Gold L et al. Role of different brain structures in the expression of the physical morphine withdrawal syndrome. J Pharmacol Exp Ther 1992; 261: 669-677
- 9 Rasmussen K, Beitner-Johnson DB, Krystal JH et al. Opiate withdrawal and the rat locus coeruleus: behavioral, electrophysiological, and biochemical correlates. J Neurosci 1990; 10: 2308-2317
- 10 Maldonado R, Koob GF. Destruction of the locus coeruleus decreases physical signs of opiate withdrawal. Brain Res 1993; 605: 128-138
- 11 Pickel VM, Joh TH, Reis DJ. A serotonergic innervation of noradrenergic neurons in nucleus locus coeruleus: demonstration by immunocytochemical localization of the transmitter specific enzymes tyrosine and tryptophan hydroxylase. Brain Res 1977; 131: 197-214
- 12 Gorea E, Adrien J. Serotonergic regulation of noradrenergic coerulean neurons: electrophysiological evidence for the involvement of 5-HT2 receptors. Eur J Pharmacol 1988; 154: 285-291
- 13 Done C, Sharp T. Evidence that 5-HT2 receptor activation decreases noradrenaline release in rat hippocampus in vivo. Br J Pharmacol 1992; 107: 240-245
- 14 Hunziker ME, Suehs BT, Bettinger TL et al. Duloxetine hydrochloride: a new dual-acting medication for the treatment of major depressive disorder. Clin Ther 2005; 27: 1126-1143
- 15 Vaishnavi SN, Nemeroff CB, Plott SJ et al. Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry 2004; 55: 320-322
- 16 Gould GG, Javors MA, Frazer A. Effect of chronic administration of duloxetine on serotonin and norepinephrine transporter binding sites in rat brain. Biol Psychiatry 2007; 61: 210-215
- 17 Carter NJ, McCormack PL. Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs 2009; 23: 523-541
- 18 Detke MJ, Wiltse CG, Mallinckrodt CH et al. Duloxetine in the acute and long-term treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Eur Neuropsychopharmacol 2004; 14: 457-470
- 19 Bellingham GA, Peng PW. Duloxetine: a review of its pharmacology and use in chronic pain management. Reg Anesth Pain Med 2010; 35: 294-303
- 20 Bardin L, Gregoire S, Aliaga M et al. Comparison of milnacipran, duloxetine and pregabalin in the formalin pain test and in a model of stress-induced ultrasonic vocalizations in rats. Neurosci Res 2010; 66: 135-140
- 21 Fuller RW, Hemrick-Luecke SK, Snoddy HD. Effects of duloxetine, an antidepressant drug candidate, on concentrations of monoamines and their metabolites in rats and mice. J Pharmacol Exp Ther 1994; 269: 132-136
- 22 Rueter LE, De Montigny C, Blier P. Electrophysiological characterization of the effect of long-term duloxetine administration on the rat serotonergic and noradrenergic systems. J Pharmacol Exp Ther 1998; 285: 404-412
- 23 Ji C-X, Fan D-S, Li W et al. Evaluation of the anti-ulcerogenic activity of the antidepressants duloxetine, amitriptyline, fluoxetine and mirtazapine in different models of experimental gastric ulcer in rats. Eur J Pharmacol 2012; 691: 46-51
- 24 Munro G. Dopamine D1 and D2 receptor agonism enhances antinociception mediated by the serotonin and noradrenaline reuptake inhibitor duloxetine in the rat formalin test. Eur J Pharmacol 2007; 575: 66-74
- 25 Grégoire S, Michaud V, Chapuy E et al. Study of emotional and cognitive impairments in mononeuropathic rats: Effect of duloxetine and gabapentin. Pain 2012; 153: 1657-1663
- 26 Parvizpour A, Charkhpour M, Habibi-Asl B et al. Repeated central administration of selegiline attenuated morphine physical dependence in rat. Pharmacol Rep 2013; 65: 593-599
- 27 Rasmussen K, Beitner-Johnson DB, Krystal JH et al. Opiate withdrawal and the rat locus coeruleus: behavioral, electrophysiological, and biochemical correlates. The Journal of Neuroscience 1990; 10: 2308-2317
- 28 Dizgah IM, Karimian SM, Zarrindast MR et al. Attenuation of morphine withdrawal signs by a D1 receptor agonist in the locus coeruleus of rats. Neuroreport 2005; 16: 1683
- 29 Riahi E, Mirzaii-Dizgah I, Karimian SM et al. Attenuation of morphine withdrawal signs by a GABAB receptor agonist in the locus coeruleus of rats. Behav Brain Res 2009; 196: 11-14
- 30 Chen SQ, Zhai HF, Cui YY et al. Clonidine attenuates morphine withdrawal and subsequent drug sensitization in rhesus monkeys. Acta Pharmacol Sin 2007; 28: 473-483
- 31 Robinson MJF, Armson M, Franklin KBJ. The effect of propranolol and midazolam on the reconsolidation of a morphine place preference in chronically treated rats. Frontiers in Behavioral Neuroscience 2011;
- 32 Navarro-Zaragoza J, Nunez C, Ruiz-Medina J et al. CRF(2) mediates the increased noradrenergic activity in the hypothalamic paraventricular nucleus and the negative state of morphine withdrawal in rats. Br J Pharmacol 2011; 162: 851-862
- 33 Lelevich SV, Lelevich VV, Novokshonov AA. Neurotransmitter mechanisms of morphine withdrawal syndrome. Bull Exp Biol Med 2009; 148: 184-187
- 34 Diaz SL, Kemmling AK, Rubio MC et al. Morphine withdrawal syndrome: involvement of the dopaminergic system in prepubertal male and female mice. Pharmacol Biochem Behav 2005; 82: 601-607
- 35 Zarrindast MR, Naghipour B, Roushan-zamir F et al. Effects of adenosine receptor agents on the expression of morphine withdrawal in mice. Eur J Pharmacol 1999; 369: 17-22
- 36 Zhu H, Barr GA. The role of AMPA and metabotropic glutamate receptors on morphine withdrawal in infant rats. Int J Dev Neurosci 2004; 22: 379-395
- 37 Roberts MHT. 5-Hydroxytryptamine and antinociception. Neuropharmacology 1984; 23: 1529-1536
- 38 Arends RH, Hayashi TG, Luger TJ et al. Cotreatment with racemic fenfluramine inhibits the development of tolerance to morphine analgesia in rats. J Pharmacol Exp Ther 1998; 286: 585-592
- 39 Jolas T, Nestler EJ, Aghajanian GK. Chronic morphine increases GABA tone on serotonergic neurons of the dorsal raphe nucleus: association with an up-regulation of the cyclic AMP pathway. Neuroscience 2000; 95: 433-443
- 40 Schoffelmeer ANM, Putters J, Mulder AH. Activation of presynaptic α2-adrenoceptors attenuates the inhibitory effect of μ-opioid receptor agonists on noradrenaline release from brain slices. Naunyn-Schmiedeberg’s Arch Pharmacol 1986; 333: 377-380
- 41 Silverstone PH, Done C, Sharp T. In vivo monoamine release during naloxone-precipitated morphine withdrawal. Neuroreport 1993; 4: 1043-1045
- 42 Aston-Jones G, Akaoka H, Charlety P et al. Serotonin selectively attenuates glutamate-evoked activation of noradrenergic locus coeruleus neurons. J Neurosci 1991; 11: 760-769
- 43 McCleane G. Antidepressants as analgesics. CNS Drugs 2008; 22: 139-156
- 44 Hill L, Schug SA. Recent advances in the pharmaceutical management of pain. Expert Review of Clinical Pharmacology 2009; 2: 543-557
- 45 Grant MM, Weiss JM. Effects of chronic antidepressant drug administration and electroconvulsive shock on locus coeruleus electrophysiologic activity. Biol Psychiatry 2001; 49: 117-129
- 46 Grandoso L, Pineda J, Ugedo L. Comparative study of the effects of desipramine and reboxetine on locus coeruleus neurons in rat brain slices. Neuropharmacology 2004; 46: 815-823
- 47 Lacroix D, Blier P, Curet O et al. Effects of long-term desipramine administration on noradrenergic neurotransmission: electrophysiological studies in the rat brain. J Pharmacol Exp Ther 1991; 257: 1081-1090
- 48 Mateo Y, Fernandez-Pastor B, Meana JJ. Acute and chronic effects of desipramine and clorgyline on alpha(2)-adrenoceptors regulating noradrenergic transmission in the rat brain: a dual-probe microdialysis study. Br J Pharmacol 2001; 133: 1362-1370
- 49 Lu L, Su WJ, Yue W et al. Attenuation of morphine dependence and withdrawal in rats by venlafaxine, a serotonin and noradrenaline reuptake inhibitor. Life Sci 2001; 69: 37-46