Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
General Research Article

Abstinence from Chronic Methylphenidate Exposure Modifies Cannabinoid Receptor 1 Levels in the Brain in a Dose-dependent Manner

Author(s): Carly Connor, John Hamilton, Lisa Robison, Michael Hadjiargyrou, David Komatsu and Panayotis Thanos*

Volume 28, Issue 4, 2022

Published on: 02 December, 2021

Page: [331 - 338] Pages: 8

DOI: 10.2174/1381612827666210127120411

Price: $65

Abstract

Introduction: Methylphenidate (MP) is a widely used psychostimulant prescribed for Attention Deficit Hyperactivity Disorder and is also used illicitly by healthy individuals. Chronic exposure to MP has been shown to affect physiology, behavior measures, and neurochemistry.

Methods: The present study examined its effect on the endocannabinoid system. Adolescent rats had daily oral access to either water (control), low dose MP (4/10 mg/kg), or high dose MP (30/60 mg/kg). After 13 weeks of exposure, half of the rats in each group were euthanized, with the remaining rats underwent a four-week- long abstinence period. Cannabinoid receptor 1 binding (CB1) was measured with in vitro autoradiography using [3H] SR141716A.

Results: Rats who underwent a 4-week abstinence period after exposure to chronic HD MP showed increased CB1 binding in several cortical and basal ganglia regions of the brain compared to rats with no abstinence period. In contrast to this, rats who underwent a 4-week abstinence period after exposure to chronic LD MP showed lower CB1 binding mainly in the basal ganglia regions and the hindlimb region of the somatosensory cortex compared to rats with no abstinence period. Following 4 weeks of drug abstinence, rats who were previously given HD MP showed higher [3H] SR141716A binding in many of the cortical and basal ganglia regions examined than rats given LD MP. These results highlight the biphasic effects of MP treatment on cannabinoid receptor levels. Abstinence from HD MP seemed to increase CB1 receptor levels, while abstinence from LD MP seemed to decrease CB1 levels.

Conclusion: Given the prolific expression of cannabinoid receptors throughout the brain, many types of behaviors may be affected as a result of MP abstinence. Further research will be needed to help identify these behavioral changes.

Keywords: Methylphenidate, ritalin, psychostimulant, endocannabinoid system, cannabinoid receptor 1, attention deficit hyperactivity disorder.

« Previous
[1]
Swanson JM, Wigal TL, Volkow ND. Contrast of medical and nonmedical use of stimulant drugs, basis for the distinction, and risk of addiction: comment on Smith and Farah (2011). Psychol Bull 2011; 137(5): 742-8.
[http://dx.doi.org/10.1037/a0024898] [PMID: 21859175]
[2]
Bogle KE, Smith BH. Illicit methylphenidate use: a review of prevalence, availability, pharmacology, and consequences. Curr Drug Abuse Rev 2009; 2(2): 157-76.
[http://dx.doi.org/10.2174/1874473710902020157] [PMID: 19630746]
[3]
McCabe SE, Teter CJ, Boyd CJ. Medical use, illicit use, and diversion of abusable prescription drugs. J Am Coll Health 2006; 54(5): 269-78.
[http://dx.doi.org/10.3200/JACH.54.5.269-278] [PMID: 16539219]
[4]
Weyandt LL, Janusis G, Wilson KG, et al. Nonmedical prescription stimulant use among a sample of college students: relationship with psychological variables. J Atten Disord 2009; 13(3): 284-96.
[http://dx.doi.org/10.1177/1087054709342212] [PMID: 19767596]
[5]
Carias E, Fricke D, Vijayashanthar A, et al. Weekday-only chronic oral methylphenidate self-administration in male rats: Reversibility of the behavioral and physiological effects. Behav Brain Res 2019; 356: 189-96.
[http://dx.doi.org/10.1016/j.bbr.2018.08.014] [PMID: 30149034]
[6]
Kalinowski L, Connor C, Somanesan R, et al. Brief and extended abstinence from chronic oral methylphenidate treatment produces reversible behavioral and physiological effects. Dev Psychobiol 2020; 62(2): 170-80.
[http://dx.doi.org/10.1002/dev.21902] [PMID: 31456229]
[7]
Carias E, Hamilton J, Robison LS, Delis F, Eiden R, Quattrin T, et al. Chronic oral methylphenidate treatment increases microglial activation in rats. J Neural Transm (Vienna, Austria : 1996) 2018; 125(12): 1867-75.
[http://dx.doi.org/10.1007/s00702-018-1931-z]
[8]
Martin C, Fricke D, Vijayashanthar A, et al. Recovery from behavior and developmental effects of chronic oral methylphenidate following an abstinence period. Pharmacol Biochem Behav 2018; 172: 22-32.
[http://dx.doi.org/10.1016/j.pbb.2018.07.001] [PMID: 30030127]
[9]
Robison LS, Ananth M, Hadjiargyrou M, Komatsu DE, Thanos PK. Chronic oral methylphenidate treatment reversibly increases striatal dopamine transporter and dopamine type 1 receptor binding in rats. J Neural Transm (Vienna, Austria : 1996) 2017; 124(5): 655-67.
[http://dx.doi.org/10.1007/s00702-017-1680-4]
[10]
Volkow ND, Wang G, Fowler JS, et al. Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain. J Neurosci 2001; 21(2): RC121.
[http://dx.doi.org/10.1523/JNEUROSCI.21-02-j0001.2001] [PMID: 11160455]
[11]
Kodama T, Kojima T, Honda Y, Hosokawa T, Tsutsui K-I, Watanabe M. Oral administration of methylphenidate (Ritalin) affects dopamine release differentially between the prefrontal cortex and striatum: A microdialysis study in the monkey. J Neurosci 2017; 37(9): 2387-94.
[http://dx.doi.org/10.1523/JNEUROSCI.2155-16.2017] [PMID: 28154152]
[12]
Dela Peña IC, Shen G, Shi W-X. Methylphenidate significantly alters the functional coupling between the prefrontal cortex and dopamine neurons in the ventral tegmental area. Neuropharmacology 2018; 131: 431-9.
[http://dx.doi.org/10.1016/j.neuropharm.2018.01.015] [PMID: 29339293]
[13]
Di Miceli M, Omoloye A, Gronier B. Chronic methylphenidate treatment during adolescence has long-term effects on monoaminergic function. J Psychopharmacol 2019; 33(1): 109-21.
[http://dx.doi.org/10.1177/0269881118805494] [PMID: 30334678]
[14]
Piomelli D. The molecular logic of endocannabinoid signalling. Nat Rev Neurosci 2003; 4(11): 873-84.
[http://dx.doi.org/10.1038/nrn1247] [PMID: 14595399]
[15]
Tsou K, Brown S, Sañudo-Peña MC, Mackie K, Walker JM. Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 1998; 83(2): 393-411.
[http://dx.doi.org/10.1016/S0306-4522(97)00436-3] [PMID: 9460749]
[16]
Burns HD, Van Laere K, Sanabria-Bohórquez S, et al. [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor. Proc Natl Acad Sci USA 2007; 104(23): 9800-5.
[http://dx.doi.org/10.1073/pnas.0703472104] [PMID: 17535893]
[17]
Tanda G, Pontieri FE, Chiara GD. Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common opioid receptor mechanism. Science 1997; 276(5321): 2048.
[http://dx.doi.org/10.1126/science.276.5321.2048] [PMID: 9197269]
[18]
French ED, Dillon K, Wu X. Cannabinoids excite dopamine neurons in the ventral tegmentum and substantia nigra. Neuroreport 1997; 8(3): 649-52.
[http://dx.doi.org/10.1097/00001756-199702100-00014] [PMID: 9106740]
[19]
Mathur BN, Lovinger DM. Endocannabinoid-dopamine interactions in striatal synaptic plasticity. Front Pharmacol 2012; 3: 66.
[http://dx.doi.org/10.3389/fphar.2012.00066] [PMID: 22529814]
[20]
Xu H, Perez S, Cornil A, et al. Dopamine-endocannabinoid interactions mediate spike-timing-dependent potentiation in the striatum. Nat Commun 2018; 9(1): 4118.
[http://dx.doi.org/10.1038/s41467-018-06409-5] [PMID: 30297767]
[21]
Socodato R. Dopamine D1 receptor signaling and endocannabinoid cooperate to fuel striatal plasticity. J Neurochem 2020.
[http://dx.doi.org/10.1111/jnc.14977]
[22]
Oleson EB, Beckert MV, Morra JT, et al. Endocannabinoids shape accumbal encoding of cue-motivated behavior via CB1 receptor activation in the ventral tegmentum. Neuron 2012; 73(2): 360-73.
[http://dx.doi.org/10.1016/j.neuron.2011.11.018] [PMID: 22284189]
[23]
Mlost J, Wąsik A, Starowicz K. Role of endocannabinoid system in dopamine signalling within the reward circuits affected by chronic pain. Pharmacol Res 2019; 143: 40-7.
[http://dx.doi.org/10.1016/j.phrs.2019.02.029] [PMID: 30831242]
[24]
Thanos PK, Robison LS, Steier J, et al. A pharmacokinetic model of oral methylphenidate in the rat and effects on behavior. Pharmacol Biochem Behav 2015; 131: 143-53.
[http://dx.doi.org/10.1016/j.pbb.2015.01.005] [PMID: 25641666]
[25]
Swenson S, Hamilton J, Robison L, Thanos PK. Chronic aerobic exercise: Lack of effect on brain CB1 receptor levels in adult rats. Life Sci 2019; 230: 84-8.
[http://dx.doi.org/10.1016/j.lfs.2019.05.058] [PMID: 31128137]
[26]
Delis F, Rosko L, Shroff A, Leonard KE, Thanos PK. Oral haloperidol or olanzapine intake produces distinct and region-specific increase in cannabinoid receptor levels that is prevented by high fat diet. Prog Neuropsychopharmacol Biol Psychiatry 2017; 79(Pt B): 268-80.
[http://dx.doi.org/10.1016/j.pnpbp.2017.06.005] [PMID: 28619471]
[27]
Thanos PK, Gopez V, Delis F, et al. Upregulation of cannabinoid type 1 receptors in dopamine D2 receptor knockout mice is reversed by chronic forced ethanol consumption. Alcohol Clin Exp Res 2011; 35(1): 19-27.
[http://dx.doi.org/10.1111/j.1530-0277.2010.01318.x] [PMID: 20958329]
[28]
Vinod KY, Yalamanchili R, Thanos PK, et al. Genetic and pharmacological manipulations of the CB(1) receptor alter ethanol preference and dependence in ethanol preferring and nonpreferring mice. Synapse 2008; 62(8): 574-81.
[http://dx.doi.org/10.1002/syn.20533] [PMID: 18509854]
[29]
Thanos PK, Ramalhete RC, Michaelides M, Piyis YK, Wang G-J, Volkow ND. Leptin receptor deficiency is associated with upregulation of cannabinoid 1 receptors in limbic brain regions. Synapse 2008; 62(9): 637-42.
[http://dx.doi.org/10.1002/syn.20531] [PMID: 18563836]
[30]
Belue RC, Howlett AC, Westlake TM, Hutchings DE. The ontogeny of cannabinoid receptors in the brain of postnatal and aging rats. Neurotoxicol Teratol 1995; 17(1): 25-30.
[http://dx.doi.org/10.1016/0892-0362(94)00053-G] [PMID: 7708016]
[31]
Mailleux P, Vanderhaeghen J-J. Age-related loss of cannabinoid receptor binding sites and mRNA in the rat striatum. Neurosci Lett 1992; 147(2): 179-81.
[http://dx.doi.org/10.1016/0304-3940(92)90589-Y] [PMID: 1491804]
[32]
Berrendero F, Sepe N, Ramos JA, Di Marzo V, Fernández-Ruiz JJ. Analysis of cannabinoid receptor binding and mRNA expression and endogenous cannabinoid contents in the developing rat brain during late gestation and early postnatal period. Synapse 1999; 33(3): 181-91.
[http://dx.doi.org/10.1002/(SICI)1098-2396(19990901)33:3<181::AID-SYN3>3.0.CO;2-R] [PMID: 10420166]
[33]
Robison LS, Michaelos M, Gandhi J, et al. Sex differences in the physiological and behavioral effects of chronic oral methylphenidate treatment in rats. Front Behav Neurosci 2017; 11: 53.
[http://dx.doi.org/10.3389/fnbeh.2017.00053] [PMID: 28400722]
[34]
Uddin SMZ, Robison LS, Fricke D, et al. Methylphenidate regulation of osteoclasts in a dose- and sex-dependent manner adversely affects skeletal mechanical integrity. Sci Rep 2018; 8(1): 1515.
[http://dx.doi.org/10.1038/s41598-018-19894-x] [PMID: 29367750]
[35]
Komatsu DE, Thanos PK, Mary MN, et al. Chronic exposure to methylphenidate impairs appendicular bone quality in young rats. Bone 2012; 50(6): 1214-22.
[http://dx.doi.org/10.1016/j.bone.2012.03.011] [PMID: 22465849]
[36]
Pillidge K, Porter AJ, Young JW, Stanford SC. Perseveration by NK1R-/- (‘knockout’) mice is blunted by doses of methylphenidate that affect neither other aspects of their cognitive performance nor the behaviour of wild-type mice in the 5-Choice Continuous Performance Test. J Psychopharmacol 2016; 30(9): 837-47.
[http://dx.doi.org/10.1177/0269881116642541] [PMID: 27097734]
[37]
Crawford CA, Der-Ghazarian T, Britt CE, Varela FA, Kozanian OO. Novelty-induced conditioned place preference, sucrose preference, and elevated plus maze behavior in adult rats after repeated exposure to methylphenidate during the preweanling period. Behav Brain Res 2013; 246: 29-35.
[http://dx.doi.org/10.1016/j.bbr.2013.02.031] [PMID: 23466690]
[38]
Trinh TN, Kohllepel SR, Yang PB, Burau KD, Dafny N. Adult female rats’ altered diurnal locomotor activity pattern following chronic methylphenidate treatment. J Neural Transm (Vienna) 2013; 120(12): 1717-31.
[http://dx.doi.org/10.1007/s00702-013-1063-4] [PMID: 23893293]
[39]
Castells X, Ramos-Quiroga JA, Rigau D, et al. Efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder: a meta-regression analysis. CNS Drugs 2011; 25(2): 157-69.
[http://dx.doi.org/10.2165/11539440-000000000-00000] [PMID: 21254791]
[40]
Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M. Endocannabinoid-mediated control of synaptic transmission. Physiol Rev 2009; 89(1): 309-80.
[http://dx.doi.org/10.1152/physrev.00019.2008] [PMID: 19126760]
[41]
Castillo PE, Younts TJ, Chávez AE, Hashimotodani Y. Endocannabinoid signaling and synaptic function. Neuron 2012; 76(1): 70-81.
[http://dx.doi.org/10.1016/j.neuron.2012.09.020] [PMID: 23040807]
[42]
Haj-Dahmane S, Shen R-Y. Modulation of the serotonin system by endocannabinoid signaling. Neuropharmacol 2011; 61(3): 414-20.
[http://dx.doi.org/10.1016/j.neuropharm.2011.02.016] [PMID: 21354188]
[43]
Crombie KM, Brellenthin AG, Hillard CJ, Koltyn KF. Endocannabinoid and opioid system interactions in exercise-induced hypoalgesia. Pain Med 2018; 19(1): 118-23.
[http://dx.doi.org/10.1093/pm/pnx058] [PMID: 28387833]
[44]
Thompson KJ, Tobin AB. Crosstalk between the M1 muscarinic acetylcholine receptor and the endocannabinoid system: A relevance for Alzheimer’s disease? Cell Signal 2020; 70: 109545.
[http://dx.doi.org/10.1016/j.cellsig.2020.109545] [PMID: 31978506]
[45]
Talarico G, Trebbastoni A, Bruno G, de Lena C. Modulation of the cannabinoid system: A new perspective for the treatment of the Alzheimer’s Disease. Curr Neuropharmacol 2019; 17(2): 176-83.
[http://dx.doi.org/10.2174/1570159X16666180702144644] [PMID: 29962346]
[46]
Mecha M, Carrillo-Salinas FJ, Feliú A, Mestre L, Guaza C. Microglia activation states and cannabinoid system: Therapeutic implications. Pharmacol Ther 2016; 166: 40-55.
[http://dx.doi.org/10.1016/j.pharmthera.2016.06.011] [PMID: 27373505]
[47]
Woodhams SG, Sagar DR, Burston JJ, Chapman V. The role of the endocannabinoid system in pain.Pain Control. Berlin, Heidelberg: Springer Berlin Heidelberg 2015; pp. 119-43.
[http://dx.doi.org/10.1007/978-3-662-46450-2_7]
[48]
Huang W-J, Chen W-W, Zhang X. Endocannabinoid system: Role in depression, reward and pain control (Review). Mol Med Rep 2016; 14(4): 2899-903.
[http://dx.doi.org/10.3892/mmr.2016.5585] [PMID: 27484193]
[49]
Lisboa SF, Gomes FV, Terzian ALB, Aguiar DC, Moreira FA, Resstel LBM, et al. Chapter Eight - The Endocannabinoidsystem and anxiety.Vitamins and Hormones. Academic Press 2017; pp. 193-279.
[50]
Micale V, Drago F. Endocannabinoid system, stress and HPA axis. Eur J Pharmacol 2018; 834: 230-9.
[http://dx.doi.org/10.1016/j.ejphar.2018.07.039] [PMID: 30036537]
[51]
Lüttke CS, Ekman M, van Gerven MAJ, de Lange FP. Preference for audiovisual speech congruency in superior temporal cortex. J Cogn Neurosci 2016; 28(1): 1-7.
[http://dx.doi.org/10.1162/jocn_a_00874] [PMID: 26351991]
[52]
Rolls ET. The cingulate cortex and limbic systems for emotion, action, and memory. Brain Struct Funct 2019; 224(9): 3001-18.
[http://dx.doi.org/10.1007/s00429-019-01945-2] [PMID: 31451898]
[53]
Schultz W. Reward functions of the basal ganglia. J Neural Trans (Vienna, Austria : 1996) 2016; 123(7): 679-93.
[http://dx.doi.org/10.1007/s00702-016-1510-0]
[54]
Berryessa CM. Attention, reward, and inhibition: symptomatic features of ADHD and issues for offenders in the criminal justice system. Atten Defic Hyperact Disord 2017; 9(1): 5-10.
[http://dx.doi.org/10.1007/s12402-016-0203-8] [PMID: 27497734]

Rights & Permissions Print Cite
Article Metrics
21
5
© 2024 Bentham Science Publishers | Privacy Policy