Generic placeholder image

Current Clinical Pharmacology

Author(s): Muhammad Farhan, Fatima Riaz, Sana Wali and Hamna Rafiq *

DOI: 10.2174/1574884713666181112123309

Cite As
Desensitization of 5-HT-1A Somatodentritic Receptors in Tryptophan Treated and Co-treated Rats Induced by Methylphenidate

Page: [125 - 131] Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

Background: Psychostimulants can induce behavioral sensitization by their chronic use. The main target for the action of these drugs is dopamine, neither epinephrine nor serotonin transporters. Serotonin is synthesized by the precursor L-tryptophan. Tryptophan and methylphenidate being 5-HT agonists, both increase the level of serotonin thereby causing desensitization of 5-HT1a receptors. The present study investigated whether behavioral sensitization induced by Methylphenidate is decreased in tryptophan administrated animals.

Methods: The Experiment was divided into 2 phases (1). Behavioral effects of repeated administration of TRP 100 mg/kg and MPD for 14 days in three groups; (i) water (ii) MPD 1.0 mg/kg (iii) TRP. To explore the locomotor effects of treatment, the activity was monitored in a familiar and novel environment. (2) Behavioral consequences of repeatedly administrated MPD (1.0 mg/kg) on pretreated TRP (100 mg/kg) and MPD (1.0 mg/kg) animals following Co-MPD and TRP for 14 days, rats were divided in three groups (i) water, (ii) MPD and (iii) TRP as mentioned in Experiment no 1. After two weeks six subgroups were assigned i.e. (i) water-saline, (ii) water- MPD, (iii) TRP-saline (iv) TRP-MPD (v) MPD-saline and (vi) MPD-MPD+TRP and treated for further 14 days. Locomotor behavior was monitored in familiar environment on the next day and in novel environment on alternate days of each administration.

Results: The Results from phase 1 showed increased activity in both (TRP and MPD) treatments. However, the results of phase 2 showed significant decrease in methylphenidate-induced behavioral sensitization by both pretreatment and co-administration with TRP.

Conclusion: The present study suggests the potential of tryptophan to decrease the risk of behavioral sensitization induced by methylphenidate.

Keywords: Behavioral sensitization, methylphenidate, tryptophan, serotonin, epilepsy, midbrain.

Graphical Abstract

[1]
Steketee JD, Kalivas PW. Drug wanting: behavioral sensitization and relapse to drug-seeking behavior. Pharmacol Rev 2011; 63(2): 348-65.
[http://dx.doi.org/10.1124/pr.109.001933] [PMID: 21490129]
[2]
Robinson TE, Becker JB. Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res 1986; 396(2): 157-98.
[http://dx.doi.org/10.1016/0165-0173(86) 90002-0] [PMID: 3527341]
[3]
Kalivas PW, Stewart J. Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity. Brain Res Brain Res Rev 1991; 16(3): 223-44.
[http://dx.doi.org/10.1016/0165-0173(91)90007-U] [PMID: 1665095]
[4]
Paulson PE, Camp DM, Robinson TE. Time course of transient behavioral depression and persistent behavioral sensitization in relation to regional brain monoamine concentrations during amphetamine withdrawal in rats. Psychopharmacology (Berl) 1991; 103(4): 480-92.
[http://dx.doi.org/10.1007/BF02244248] [PMID: 2062986]
[5]
Post RM, Contel NR. Human and animal studies of cocaine: implications for development of behavioral pathology, in Stimulants: Neurochemical, Behavioral, and Clinical Perspec-tives. Creese I, editor. Ed. 1983; pp 169-203.
[6]
Yang PB, Atkins KD, Dafny N. Behavioral sensitization and cross-sensitization between methylphenidate amphetamine, and 3,4-Methylenedioxymethamphetamine (MDMA) in female SD rats. Eur J Pharmacol 2011; 661(1-3): 72-85.
[http://dx.doi.org/10.1016/j.ejphar.2011.04.035] [PMID: 21549116]
[7]
Haleem DJ. Extending therapeutic use of psychostimulants: focus on serotonin-1A receptor. Prog Neuropsychopharmacol Biol Psychiatry 2013; 46: 170-80.
[http://dx.doi.org/10.1016/j.pnpbp.2013.07.015] [PMID: 23906987]
[8]
Kirby LG, Zeeb FD, Winstanley CA. Contributions of serotonin in addiction vulnerability. Neuropharmacology 2011; 61(3): 421-32.
[http://dx.doi.org/10.1016/j.neuropharm.2011.03.022] [PMID: 21466815]
[9]
Holmes A. Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease. Neurosci Biobehav Rev 2008; 32(7): 1293-314.
[http://dx.doi.org/10.1016/j.neubiorev.2008.03.006] [PMID: 18439676]
[10]
Ghai K, Zelinka C, Fischer AJ. Serotonin released from amacrine neurons is scavenged and degraded in bipolar neurons in the retina. J Neurochem 2009; 111(1): 1-14.
[http://dx.doi.org/10.1111/j.1471-4159.2009.06270.x] [PMID: 19619137]
[11]
Jacobs BL, Azmitia EC. Structure and function of the brain serotonin system. Physiol Rev 1992; 72(1): 165-229.
[http://dx.doi.org/10.1152/physrev.1992.72.1.165] [PMID: 1731370]
[12]
Kode A, Mosialou I, Silva BC, et al. FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin. J Clin Invest 2012; 122(10): 3490-503.
[http://dx.doi.org/10.1172/JCI64906] [PMID: 22945629]
[13]
Bethea CL, Lima FB, Centeno ML, et al. Effects of citalopram on serotonin and CRF systems in the midbrain of primates with differences in stress sensitivity. J Chem Neuroanat 2011; 41(4): 200-18.
[http://dx.doi.org/10.1016/j.jchemneu.2011.05.010] [PMID: 21683135]
[14]
Baganz NL, Blakely RDA. A dialogue between the immune system and brain, spoken in the language of serotonin. ACS Chem Neurosci 2013; 4(1): 48-63.
[http://dx.doi.org/10.1021/cn300186b] [PMID: 23336044]
[15]
Nichols DE, Nichols CD. Serotonin receptors. Chem Rev 2008; 108(5): 1614-41.
[http://dx.doi.org/10.1021/cr078224o] [PMID: 18476671]
[16]
Daubert EA, Condron BG. Serotonin: a regulator of neuronal morphology and circuitry. Trends Neurosci 2010; 33(9): 424-34.
[http://dx.doi.org/10.1016/j.tins.2010.05.005] [PMID: 20561690]
[17]
Paterson LM, Kornum BR, Nutt DJ, Pike VW, Knudsen GM. 5-HT radioligands for human brain imaging with PET and SPECT. Med Res Rev 2013; 33(1): 54-111.
[http://dx.doi.org/10.1002/med.20245] [PMID: 21674551]
[18]
Schmitt JAJ, Wingen M, Ramaekers JG, Evers EAT, Riedel WJ. Serotonin and human cognitive performance. Curr Pharm Des 2006; 12(20): 2473-86.
[http://dx.doi.org/10.2174/138161206777698909] [PMID: 16842171]
[19]
Charnay Y, Léger L. Brain serotonergic circuitries. Dialogues Clin Neurosci 2010; 12(4): 471-87.
[PMID: 21319493]
[20]
Blier P, de Montigny C, Chaput Y. A role for the serotonin system in the mechanism of action of antidepressant treatments: preclinical evidence. J Clin Psychiatry 1990; 51(4)(Suppl.): 14-20.
[PMID: 2157700]
[21]
Haleem DJ. Serotonergic mechanism of antidepressant action and adaptation to stress. J Coll Physicians Surg Pak 1999; 9: 139-46.
[22]
Ikram H, Haleem DJ. Attenuation of apomorphine-induced sensitization by buspirone. Pharmacol Biochem Behav 2011; 99(3): 444-50.
[http://dx.doi.org/10.1016/j.pbb.2011.04.007] [PMID: 21530573]
[23]
Steiner H, Van Waes V, Marinelli M. Fluoxetine potentiates methylphenidate-induced gene regulation in addiction-related brain regions: concerns for use of cognitive enhancers? Biol Psychiatry 2010; 67(6): 592-4.
[http://dx.doi.org/10.1016/j.biopsych.2009.10.004] [PMID: 19931852]