Possible Role of Cyclic AMP Response Element Binding/Brain-Derived Neurotrophic Factor Signaling Pathway in Mediating the Pharmacological Effects of Duloxetine against Methamphetamine Use-Induced Cognitive Impairment and Withdrawal-Induced Anxiety and Depression in Rats

Ramezany Yasuj, Sanaz; Nourhashemi, Mona; Keshavarzi, Saghar; Motaghinejad, Majid; Motevalian, Manijeh

Possible Role of Cyclic AMP Response Element Binding/Brain-Derived Neurotrophic Factor Signaling Pathway in Mediating the Pharmacological Effects of Duloxetine against Methamphetamine Use-Induced Cognitive Impairment and Withdrawal-Induced Anxiety and Depression in Rats

Authors

¹ Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

² Research Center for Addiction and Risky Behaviors (ReCARB), Iran Psychiatric Center, Iran University of Medical Sciences, Tehran, Iran

Abstract

Background: Duloxetine is used for treating depression and anxiety. The current study evaluated the effects of duloxetine against methamphetamine withdrawal-induced anxiety, depression, and motor disturbances and methamphetamine use-induced cognitive impairments. Materials and Methods: Ninety-six adult male rats were used for two independent experiments. Each experiment consisted of Groups 1 and 2 which received normal saline (0.2 ml/rat) and methamphetamine (10 mg/kg) respectively, Groups 3, 4, and 5 received both methamphetamine and duloxetine at doses of 5, 10, and 15 mg/kg, respectively. Groups 6, 7, and 8 received 5, 10, and 15 mg/kg of duloxetine, respectively. All administrations were performed for 21 days. In experiment 1, elevated plus maze (EPM), open-field test (OFT), forced swim test (FST), and tail suspension test (TST) were used to examine anxiety and depression in animals during withdrawal period. In experiment 2, Morris water maze (MWM) test was used to assess the effect of methamphetamine use followed by duloxetine treatment, on learning and memory. In the experiments, the expression of cyclic AMP response element binding (CREB) and brain-derived neurotrophic factor (BDNF) proteins were evaluated using enzyme-linked immunosorbent assay. Results: In the first experiment, duloxetine at all doses attenuated methamphetamine withdrawal induced-depression, anxiety, and motor disturbances in FST, OFT, EPM, and TST. In the second experiment, duloxetine at all doses attenuated methamphetamine use-induced cognitive impairment in MWM. In both experiments, duloxetine activated cAMP, CREB, and BDNF proteins' expression in methamphetamine-treated rats. Conclusions: Duloxetine can protect the brain against methamphetamine withdrawal-induced mood and motor disturbances and can also inhibit methamphetamine-induced cognitive impairment, possibly via cAMP/CREB/BDNF signaling pathway.

Keywords

References

1.	Thrash B, Karuppagounder SS, Uthayathas S, Suppiramaniam V, Dhanasekaran M. Neurotoxic effects of methamphetamine. Neurochem Res 2010;35:171-9.
2.	Nordahl TE, Salo R, Leamon M. Neuropsychological effects of chronic methamphetamine use on neurotransmitters and cognition: A review. J Neuropsychiatry Clin Neurosci 2003;15:317-25.
3.	Brecht ML, O'Brien A, von Mayrhauser C, Anglin MD. Methamphetamine use behaviors and gender differences. Addict Behav 2004;29:89-106.
4.	Narita M, Aoki K, Takagi M, Yajima Y, Suzuki T. Implication of brain-derived neurotrophic factor in the release of dopamine and dopamine-related behaviors induced by methamphetamine. Neuroscience 2003;119:767-75.
5.	Simon SL, Domier C, Carnell J, Brethen P, Rawson R, Ling W, et al. Cognitive impairment in individuals currently using methamphetamine. Am J Addict 2000;9:222-31.
6.	Kalechstein AD, Newton TF, Green M. Methamphetamine dependence is associated with neurocognitive impairment in the initial phases of abstinence. J Neuropsychiatry Clin Neurosci 2003;15:215-20.
7.	Srisurapanont M, Ali R, Marsden J, Sunga A, Wada K, Monteiro M, et al. Psychotic symptoms in methamphetamine psychotic in-patients. Int J Neuropsychopharmacol 2003;6:347-52.
8.	Zweben JE, Cohen JB, Christian D, Galloway GP, Salinardi M, Parent D, et al. Psychiatric symptoms in methamphetamine users. Am J Addict 2004;13:181-90.
9.	Cadet JL, Krasnova IN. Molecular bases of methamphetamine-induced neurodegeneration. Int Rev Neurobiol 2009;88:101-19.
10.	Guillot TS, Shepherd KR, Richardson JR, Wang MZ, Li Y, Emson PC, et al. Reduced vesicular storage of dopamine exacerbates methamphetamine-induced neurodegeneration and astrogliosis. J Neurochem 2008;106:2205-17.
11.	Raskin J, Wiltse CG, Siegal A, Sheikh J, Xu J, Dinkel JJ, et al. Efficacy of duloxetine on cognition, depression, and pain in elderly patients with major depressive disorder: An 8-week, double-blind, placebo-controlled trial. Am J Psychiatry 2007;164:900-9.
12.	Greer TL, Sunderajan P, Grannemann BD, Kurian BT, Trivedi MH. Does duloxetine improve cognitive function independently of its antidepressant effect in patients with major depressive disorder and subjective reports of cognitive dysfunction? Depress Res Treat 2014;2014:627863.
13.	Thor KB, Katofiasc MA. Effects of duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, on central neural control of lower urinary tract function in the chloralose-anesthetized female cat. J Pharmacol Exp Ther 1995;274:1014-24.
14.	Ji D, Gilpin NW, Richardson HN, Rivier CL, Koob GF. Effects of naltrexone, duloxetine, and a corticotropin-releasing factor type 1 receptor antagonist on binge-like alcohol drinking in rats. Behav Pharmacol 2008;19:1-2.
15.	Blendy JA. The role of CREB in depression and antidepressant treatment. Biol Psychiatry 2006;59:1144-50.
16.	Lee B, Butcher GQ, Hoyt KR, Impey S, Obrietan K. Activity-dependent neuroprotection and cAMP response element-binding protein (CREB): Kinase coupling, stimulus intensity, and temporal regulation of CREB phosphorylation at serine 133. J Neurosci 2005;25:1137-48.
17.	Motaghinejad M, Motevalian M, Falak R, Heidari M, Sharzad M, Kalantari E, et al. Neuroprotective effects of various doses of topiramate against methylphenidate-induced oxidative stress and inflammation in isolated rat amygdala: The possible role of CREB/BDNF signaling pathway. J Neural Transm (Vienna) 2016;123:1463-77.
18.	Motaghinejad M, Motevalian M, Fatima S, Hashemi H, Gholami M. Curcumin confers neuroprotection against alcohol-induced hippocampal neurodegeneration via CREB-BDNF pathway in rats. Biomed Pharmacother 2017;87:721-40.
19.	Motaghinejad M, Motevalian M, Fatima S, Faraji F, Mozaffari S. The neuroprotective effect of curcumin against nicotine-induced neurotoxicity is mediated by CREB-BDNF signaling pathway. Neurochem Res 2017;42:2921-32.
20.	Clemens KJ, Van Nieuwenhuyzen PS, Li KM, Cornish JL, Hunt GE, McGregor IS, et al. MDMA (“ecstasy“), methamphetamine and their combination: Long-term changes in social interaction and neurochemistry in the rat. Psychopharmacology (Berl) 2004;173:318-25.
21.	Yamamoto Y, Yamamoto K, Hayase T, Abiru H, Shiota K, Mori C, et al. Methamphetamine induces apoptosis in seminiferous tubules in male mice testis. Toxicol Appl Pharmacol 2002;178:155-60.
22.	Iyengar S, Webster AA, Hemrick-Luecke SK, Xu JY, Simmons RM. Efficacy of duloxetine, a potent and balanced serotonin-norepinephrine reuptake inhibitor in persistent pain models in rats. J Pharmacol Exp Ther 2004;311:576-84.
23.	Motaghinejad M, Motevalian M, Larijani SF, Khajehamedi Z. Protective effects of forced exercise against methylphenidate-induced anxiety, depression and cognition impairment in rat. Adv Biomed Res 2015;4:134. [PUBMED] [Full text]
24.	Motaghinejad M, Fatima S, Karimian M, Ganji S. Protective effects of forced exercise against nicotine-induced anxiety, depression and cognition impairment in rat. J Basic Clin Physiol Pharmacol 2016;27:19-27.
25.	Petit-Demouliere B, Chenu F, Bourin M. Forced swimming test in mice: A review of antidepressant activity. Psychopharmacology (Berl) 2005;177:245-55.
26.	Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2007;2:322-8.
27.	Motaghinejad M, Motevalian M, Abdollahi M, Heidari M, Madjd Z. Topiramate confers neuroprotection against methylphenidate-induced neurodegeneration in dentate gyrus and CA1 regions of hippocampus via CREB/BDNF pathway in rats. Neurotox Res 2017;31:373-99.
28.	Chen G, Bower KA, Ma C, Fang S, Thiele CJ, Luo J, et al. Glycogen synthase kinase 3beta (GSK3beta) mediates 6-hydroxydopamine-induced neuronal death. FASEB J 2004;18:1162-4.
29.	Volkow ND, Chang L, Wang GJ, Fowler JS, Leonido-Yee M, Franceschi D, et al. Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. Am J Psychiatry 2001;158:377-82.
30.	Ereshefsky L, Dugan D. Review of the pharmacokinetics, pharmacogenetics, and drug interaction potential of antidepressants: Focus on venlafaxine. Depress Anxiety 2000;12 Suppl 1:30-44.
31.	Motaghinejad M, Ebrahimzadeh A, Shabab B. Preventive effect of central administration of venlafaxine on morphine physical dependence, nociception, and blood cortisol level in rat. Int J Prev Med 2014;5:1422-31.
32.	Hysek CM, Simmler LD, Nicola VG, Vischer N, Donzelli M, Krähenbühl S, et al. Duloxetine inhibits effects of MDMA (“ecstasy”) in vitro and in humans in a randomized placebo-controlled laboratory study. PLoS One 2012;7:e36476.
33.	Motaghinejad M, Motevalian M, Ebrahimzadeh A, Larijani SF, Khajehamedi Z. Reduction of methylphenidate induced anxiety, depression and cognition impairment by various doses of venlafaxine in rat. Int J Prev Med 2015;6:52. [PUBMED] [Full text]
34.	Hartford J, Kornstein S, Liebowitz M, Pigott T, Russell J, Detke M, et al. Duloxetine as an SNRI treatment for generalized anxiety disorder: Results from a placebo and active-controlled trial. Int Clin Psychopharmacol 2007;22:167-74.
35.	Dugan SE, Fuller MA. Duloxetine: A dual reuptake inhibitor. Ann Pharmacother 2004;38:2078-85.
36.	Krasnova IN, Justinova Z, Ladenheim B, Jayanthi S, McCoy MT, Barnes C, et al. Methamphetamine self-administration is associated with persistent biochemical alterations in striatal and cortical dopaminergic terminals in the rat. PLoS One 2010;5:e8790.
37.	Westanmo AD, Gayken J, Haight R. Duloxetine: A balanced and selective norepinephrine- and serotonin-reuptake inhibitor. Am J Health Syst Pharm 2005;62:2481-90.
38.	Stahl SM, Grady MM, Moret C, Briley M. SNRIs: Their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants. CNS Spectr 2005;10:732-47.
39.	Lee YC, Chen PP. A review of SSRIs and SNRIs in neuropathic pain. Expert Opin Pharmacother 2010;11:2813-25.
40.	Gorman JM, Kent JM. SSRIs and SNRIs: broad spectrum of efficacy beyond major depression. InAssessing Antidepressant Efficacy: A Reexamination., Jan, 1998, Phoenix, AZ, US 1999. Physicians Postgraduate Press.
41.	Mioranzza S, Costa MS, Botton PH, Ardais AP, Matte VL, Espinosa J, et al. Blockade of adenosine A (1) receptors prevents methylphenidate-induced impairment of object recognition task in adult mice. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:169-76.
42.	LeBlanc-Duchin D, Taukulis HK. Chronic oral methylphenidate induces post-treatment impairment in recognition and spatial memory in adult rats. Neurobiol Learn Mem 2009;91:218-25.
43.	LeBlanc-Duchin D, Taukulis HK. Chronic oral methylphenidate administration to periadolescent rats yields prolonged impairment of memory for objects. Neurobiol Learn Mem 2007;88:312-20.
44.	Lineberry TW, Bostwick JM. Methamphetamine abuse: A perfect storm of complications. Mayo Clin Proc 2006;81:77-84.
45.	Dai MH, Li DQ, Han Y. Effect of venlafaxine on cognitive function and hippocampal brain-derived neurotrophic factor expression in rats with post-stroke depression. Zhejiang Da Xue Xue Bao Yi Xue Ban 2011;40:527-34.
46.	Siepmann T, Mueck-Weymann M, Oertel R, Kirch W, Pittrow D, Siepmann M, et al. The effects of venlafaxine on cognitive functions and quantitative EEG in healthy volunteers. Pharmacopsychiatry 2008;41:146-50.
47.	Motaghinejad M, Motevalian M, Fatima S, Beiranvand T, Mozaffari S. Topiramate via NMDA, AMPA/kainate, GABAA and alpha2 receptors and by modulation of CREB/BDNF and akt/GSK3 signaling pathway exerts neuroprotective effects against methylphenidate-induced neurotoxicity in rats. J Neural Transm (Vienna) 2017;124:1369-87.
48.	Carlezon WA Jr., Duman RS, Nestler EJ. The many faces of CREB. Trends Neurosci 2005;28:436-45.
49.	Motaghinejad M, Seyedjavadein Z, Motevalian M, Asadi M. The neuroprotective effect of lithium against high dose methylphenidate: Possible role of BDNF. Neurotoxicology 2016;56:40-54.
50.	Jarosik J, Legutko B, Unsicker K, von Bohlen Und Halbach O. Antidepressant-mediated reversal of abnormal behavior and neurodegeneration in mice following olfactory bulbectomy. Exp Neurol 2007;204:20-8.

Advanced Biomedical Research