Abstract
Methylphenidate (MPH) is a very effective treatment option for children and adolescents with attention-deficit/hyperactivity disorder. Nevertheless, there have been inconsistent reports regarding the effects of MPH on learning and memory. The aim of this study was to evaluate whether the treatment with MPH during the morning differs from that during the night on learning and memory (short and long term) in young and adult male Wistar rats. The animals received once daily intraperitoneal injection of either MPH (2 mg/kg) or saline (0.9%) for 28 days (either in the morning or at night). The animals underwent two behavioral tasks to evaluate learning and memory: inhibitory avoidance task and continuous multiple trials step-down inhibitory avoidance (CMIA). Young rats treated in the morning showed significant impaired long-term memory for inhibitory avoidance training and facilitated acquisition in the CMIA. Adult rats treated in the night showed impaired long-term retention in the CMIA. We observed similar performances in both tests for young rats treated at night or adult rats treated in the morning. Our results suggest that age and time of treatment can alter the MPH effects in learning and memory.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Altun M, Bergman E, Edstrom E, Johnson H, Ulfhake B (2007) Behavioral impairments of the aging rat. Physiol Behav 92:911–923
Andreazza AC, Frey BN, Valvassori SS et al (2007) DNA damage in rats after treatment with methylphenidate. Prog Neuropsychopharmacol Biol Psychiatry 31:1282–1288
Arnsten AF, Dudley AG (2005) Methylphenidate improves prefrontal cortical cognitive function through alpha2 adrenoceptor and dopamine D1 receptor actions: relevance to therapeutic effects in attention deficit hyperactivity disorder. Behav Brain Funct 1:2
Bolanos CA, Barrot M, Berton O, Wallace-Black D, Nestler EJ (2003) Methylphenidate treatment during pre- and periadolescence alters behavioral responses to emotional stimuli at adulthood. Biol Psychiatry 54:1317–1329
Chuhan YS, Taukulis HK (2006) Impairment of single-trial memory formation by oral methylphenidate in the rat. Neurobiol Learn Mem 85:125–131
Elliott R, Sahakian BJ, Matthews K et al (1997) Effects of methylphenidate on spatial working memory and planning in healthy young adults. Psychopharmacology (Berl) 131:196–206
Fagundes AO, Rezin GT, Zanette F et al (2007) Chronic administration of methylphenidate activates mitochondrial respiratory chain in brain of young rats. Int J Dev Neurosci 25:47–51
Gaytan O, Yang P, Swann A, Dafny N (2000) Diurnal differences in sensitization to methylphenidate. Brain Res 864:24–39
Gerasimov MR, Franceschi M, Volkow ND et al (2000) Comparison between intraperitoneal and oral methylphenidate administration: a microdialysis and locomotor activity study. J Pharmacol Exp Ther 295:51–57
Gomes KM, Petronilho FC, Mantovani M et al (2008) Antioxidant enzyme activities following acute or chronic methylphenidate treatment in young rats. Neurochem Res 33:1024–1027
Gomes KM, Souza RP, Valvassori SS et al (2009) Chronic methylphenidate-effects over circadian cycle of young and adult rats submitted to open-field and object recognition tests. Curr Neurovasc Res 6:259–266
Heyser CJ, Pelletier M, Ferris JS (2004) The effects of methylphenidate on novel object exploration in weanling and periadolescent rats. Ann N Y Acad Sci 1021:465–469
Izquierdo I, Medina JH (1995) Correlation between the pharmacology of long-term potentiation and the pharmacology of memory. Neurobiol Learn Mem 63:19–32
Izquierdo I, Medina JH (1997) Memory formation: the sequence of biochemical events in the hippocampus and its connection to activity in other brain structures. Neurobiol Learn Mem 68:285–316
Kafka MS, Wirz-Justice A, Naber D (1981) Circadian and seasonal rhythms in alpha- and beta-adrenergic receptors in the rat brain. Brain Res 207:409–419
Kuczenski R, Segal DS (2002) Exposure of adolescent rats to oral methylphenidate: preferential effects on extracellular norepinephrine and absence of sensitization and cross-sensitization to methamphetamine. J Neurosci 22:7264–7271
LeBlanc-Duchin D, Taukulis HK (2007) Chronic oral methylphenidate administration to periadolescent rats yields prolonged impairment of memory for objects. Neurobiol Learn Mem 88:312–320
Lemmer B, Berger T (1978) Diurnal rhythm in the central dopamine turnover in the rat. Naunyn Schmiedebergs Arch Pharmacol 303:257–261
Martins MR, Reinke A, Petronilho FC et al (2006) Methylphenidate treatment induces oxidative stress in young rat brain. Brain Res 1078:189–197
Peterson K, McDonagh MS, Fu R (2008) Comparative benefits and harms of competing medications for adults with attention-deficit hyperactivity disorder: a systematic review and indirect comparison meta-analysis. Psychopharmacology (Berl) 197:1–11
Quinn D (2008) Does chirality matter? Pharmacodynamics of enantiomers of methylphenidate in patients with attention-deficit/hyperactivity disorder. J Clin Psychopharmacol 28:S62–S66
Scaini G, Fagundes AO, Rezin GT et al (2008) Methylphenidate increases creatine kinase activity in the brain of young and adult rats. Life Sci 83:795–800
Scherer EB, Matte C, Ferreira AG et al (2009) Methylphenidate treatment increases Na(+), K (+)-ATPase activity in the cerebrum of young and adult rats. J Neural Transm 116:1681–1687
Scheving LE, Vedral DF, Pauly JE (1968) Daily circadian rhythm in rats to d-amphetamine sulphate: effect of blinding and continuous illumination on the rhythm. Nature 219:621–622
Schiffer WK, Volkow ND, Fowler JS et al (2006) Therapeutic doses of amphetamine or methylphenidate differentially increase synaptic and extracellular dopamine. Synapse 59:243–251
Smolensky MH, D’Alonzo GE (1993) Medical chronobiology: concepts and applications. Am Rev Respir Dis 147:S2–S19
Souza RP, Soares EC, Rosa DV et al (2008) Methylphenidate alters NCS-1 expression in rat brain. Neurochem Int 53:12–16
Souza RP, Soares EC, Rosa DV et al (2009) Cerebral DARPP-32 expression after methylphenidate administration in young and adult rats. Int J Dev Neurosci 27:1–7
Thai DL, Yurasits LN, Rudolph GR, Perel JM (1999) Comparative pharmacokinetics and tissue distribution of the d-enantiomers of para-substituted methylphenidate analogs. Drug Metab Dispos 27:645–650
Tuon L, Comim CM, Petronilho F et al (2008) Time-dependent behavioral recovery after sepsis in rats. Intensive Care Med 34:1724–1731
Volkow ND, Ding YS, Fowler JS et al (1995) Is methylphenidate like cocaine? Studies on their pharmacokinetics and distribution in the human brain. Arch Gen Psychiatry 52:456–463
Volkow ND, Wang GJ, Fowler JS et al (1998) Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry 155:1325–1331
Volkow ND, Fowler JS, Wang G, Ding Y, Gatley SJ (2002) Mechanism of action of methylphenidate: insights from PET imaging studies. J Atten Disord 6 Suppl (1):S31–S43
Wilens TE (2008) Pharmacotherapy of ADHD in adults. CNS Spectr 13:11–13
Acknowledgments
This research was supported by grants from CNPq, FAPESC and UNESC. JQ is a CNPq Research Fellow. SSV is the holder of a CAPES studentship, CMC of a CNPq studentship, and GZR of a FAPESC studentship. RPS is the holder of a CIHR # postdoctoral fellowship #93967.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gomes, K.M., Comim, C.M., Valvassori, S.S. et al. Diurnal differences in memory and learning in young and adult rats treated with methylphenidate. J Neural Transm 117, 457–462 (2010). https://doi.org/10.1007/s00702-010-0385-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-010-0385-8