Hostname: page-component-cd9895bd7-gvvz8 Total loading time: 0 Render date: 2024-12-19T00:03:00.306Z Has data issue: false hasContentIssue false
  • English
  • Français

Methylphenidate treatment affects mitogen-activated protein kinase activation in the striatum of young rats

Published online by Cambridge University Press:  07 March 2013

Clarissa M. Comim ,
Josimar G. Pereira ,
Sandro J. Ribeiro ,
João Quevedo  and
Carina R. Boeck
Clarissa M. Comim
Affiliation:
Laboratory of Neurosciences and National Institute for Translational Medicine (INCT-TM), Postgradute Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil
Josimar G. Pereira
Affiliation:
Laboratory of Neurosciences and National Institute for Translational Medicine (INCT-TM), Postgradute Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil
Sandro J. Ribeiro
Affiliation:
Laboratory of Neurosciences and National Institute for Translational Medicine (INCT-TM), Postgradute Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil
João Quevedo
Affiliation:
Laboratory of Neurosciences and National Institute for Translational Medicine (INCT-TM), Postgradute Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil
Carina R. Boeck*
Affiliation:
Laboratory of Neurosciences and National Institute for Translational Medicine (INCT-TM), Postgradute Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil
*
Dr. Carina R. Boeck, Laboratório de Neurociências, PPGCS, UNASAU, Universidade do Extremo Sul Catarinense, Av. Universitária - 1106, Bairro Universitária, 88806-000 Criciúma, SC, Brazil. Fax: +55 48 3431 2758; E-mail [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

Methylphenidate (MPD) is a drug prescribed for the treatment of attention deficit/hyperactivity disorder and its therapeutic effect is attributed to the inhibition of dopamine.

Methods

Young male Wistar rats were administered MPD (1, 2, 5, or 10 mg/kg) once a day or an intraperitoneal injection of saline for 28 days (chronic treatment) or for 1 day (acute treatment). Two hours after the last administration the animals were decapitated and their striatum was dissected.

Results

In this work, we show that continued treatment with MPD is capable of modifying the levels of phosphorylation of proteins JNK1/2 (c-Jun amino-terminal kinases 1 and 2) and ERK1/2 (extracellular signal-regulated kinases 1 and 2). Whereas the level of phosphorylation of protein ERK increased significantly, that of proteins JNK1/2 diminished.

Conclusion

The alteration in the level of activation of mitogen-activated protein kinases can be a molecular mechanism through which MPD exerts its therapeutic effect.

Keywords

ERKJNKMAPKmethylphenidatestriatum
Type
Short Communications
Information
Acta Neuropsychiatrica , Volume 25 , Issue 4 , August 2013 , pp. 235 - 239
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Peterson, K, McDonagh, MS, Fu, R. Comparative benefits and harms of competing medications for adults with attention-deficit hyperactivity disorder: a systematic review and indirect comparison meta-analysis. Psychopharmacology 2008;197:1–11.Google Scholar
2.Wilens, TE. Pharmacotherapy of ADHD in adults. CNS Spectr 2008;13:11–13.Google Scholar
3.Quinn, D. Does chirality matter? Pharmacodynamics of enantiomers of methylphenidate in patients with attention-deficit/hyperactivity disorder. J Clin Psychopharmacol 2008;28:S62–S66.Google Scholar
4.Davis, S, Vanhoutte, P, Pages, C, Caboche, J, Laroche, S. The MAPK/ERK cascade targets both Elk-1 and cAMP response element-binding protein to control long-term potentiation-dependent gene expression in the dentate gyrus in vivo. J Neurosci 2000;20:4563–4572.Google Scholar
5.Sweatt, JD. The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory. J Neurochem 2001;76:1–10.CrossRefGoogle ScholarPubMed
6.Wang, YZ, Bonner, JC. Mechanism of extracellular signal-regulated kinase (ERK)-1 and ERK-2 activation by vanadium pentoxide in rat pulmonary myofibroblasts. Am J Respir Cell Mol Biol 2000;22:590–596.Google Scholar
7.Beaulieu, JM, Sotnikova, TD, Gainetdinov, RR, Caron, MG. Paradoxical striatal cellular signaling responses to psychostimulants in hyperactive mice. J Biol Chem 2006;281:32072–32080.Google Scholar
8.Andreazza, AC, Frey, BN, Valvassori, SS, et al. DNA damage in rats after treatment with methylphenidate. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:1282–1288.Google Scholar
9.Scherer, EB, Matté, C, Ferreira, AG, et al. Methylphenidate treatment increases Na(+), K(+)-ATPase activity in the cerebrum of young and adult rats. J Neural Transm 2009;116:1681–1687.Google Scholar
10.Gomes, KM, Souza, RP, Valvassori, SS, et al. Chronic methylphenidate-effects over circadian cycle of young and adult rats submitted to open-field and object recognition tests. Curr Neurovasc Res 2009;6:259–266.Google Scholar
11.Gomes, KM, Comim, CM, Valvassori, SS, et al. Diurnal differences in memory and learning in young and adult rats treated with methylphenidate. J Neural Transm 2010;117:457–462.Google Scholar
12.Gomes, KM, Souza, RP, Inácio, CG, et al. Evaluation of light/dark cycle in anxiety- and depressive like behaviors after regular treatment with methylphenidate hydrochloride in rats of different ages. Rev Bras Psiquiatr 2011;33:55–58.Google Scholar
13.Konradi, C, Cole, RL, Heckers, S, Hyman, SE. Amphetamine regulates gene expression in rat striatum via transcription factor CREB. J Neurosci 1994;14:5623–5634.Google Scholar
14.Adams, DH, Hanson, GR, Keefe, KA. Psychostimulants activate p42/44 MAPK in dorsal and ventral striatum. Soc Neurosci Abstr 2001;27:445–452.Google Scholar
15.Shen, C, Tsimberg, Y, Salvadore, C, Meller, E. Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions. BMC Neurosci 2004;5:1–13.Google Scholar
16.Bolaños, CA, Barrot, M, Berton, O, Wallace-Black, D, Nestler, EJ. Methylphenidate treatment during pre- and periadolescence alters behavioural responses to emotional stimuli at adulthood. Biol Psychiatry 2003;54:1317–1329.CrossRefGoogle ScholarPubMed
17.Saporito, MS, Hudkins, RL, Maroney, AC. Discovery of CEP-1347/KT-7515, an inhibitor of the JNK/SAPK pathway for the treatment of neurodegenerative diseases. Prog Med Chem 2002;40:23–62.CrossRefGoogle ScholarPubMed
18.Vlahopoulos, S, Zoumpourlis, VC. JNK: a key modulator of intracellular signaling. Biochemistry (Moscow) 2004;69:844–854.Google Scholar
19.Brandon, CL, Steiner, H. Repeated methylphenidate treatment in adolescent rats alters gene regulation in the striatum. Eur J Neurosci 2003;18:1584–1592.Google Scholar
20.Eriksson, M, Taskinen, M, Leppä, S. Mitogen activated protein kinase dependent activation of c-Jun and c-Fos is required for neuronal differentiation but not for growth and stress response in PC12 cells. J Cell Physiol 2007;210:538–548.Google Scholar
21.Martins, MR, Reinke, A, Petronilho, FC, Gomes, KM, Dal-Pizzol, F, Quevedo, J. Methylphenidate treatment induces oxidative stress in young rat brain. Brain Res 2006;1078:189–197.Google Scholar
22.Fagundes, AO, Rezin, GT, Zanette, F, et al. Chronic administration of methylphenidate activates mitochondrial respiratory chain in brain of young rats. Int J Dev Neurosci 2007;25:47–51.Google Scholar
23.Scaini, G, Fagundes, AO, Rezin, GT, et al. Methylphenidate increases creatine kinase activity in the brain of young and adult rats. Life Sci 2008;5:795–800.Google Scholar
24.Veetil, PK, Mukkadan, JK. Effect of methylphenidate on enhancement of spatial learning by novel alternated dual task. Indian J Physiol Pharmacol 2011;55:176–182.Google Scholar
25.Mioranzza, S, Costa, MS, Botton, PH, et al. Blockade of adenosine A(1) receptors prevents methylphenidate-induced impairment of object recognition task in adult mice. Prog Neuropsychopharmacol Biol Psychiatry 2011;15:169–176.Google Scholar
26.Scherer, EB, da Cunha, MJ, Matté, C, Schmitz, F, Netto, CA, Wyse, AT. Methylphenidate affects memory, brain-derived neurotrophic factor immunocontent and brain acetylcholinesterase activity in the rat. Neurobiol Learn Mem 2010;94:247–253.Google Scholar