Vilazodone, a Selective Serotonin Reuptake Inhibitor with Diminished Impact on Methylphenidate-Induced Gene Regulation in the Striatum: Role of 5-HT1A Receptor.
Fluoxetine
Gene expression
Methylphenidate
Psychostimulant
SSRI
Striatum
Vilazodone
zif268
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
09 Oct 2023
09 Oct 2023
Historique:
received:
01
05
2023
accepted:
01
10
2023
medline:
9
10
2023
pubmed:
9
10
2023
entrez:
8
10
2023
Statut:
aheadofprint
Résumé
Selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, are frequently combined with medical psychostimulants such as methylphenidate (Ritalin), for example, in the treatment of attention-deficit hyperactivity disorder/depression comorbidity. Co-exposure to these medications also occurs with misuse of methylphenidate as a recreational drug by patients on SSRIs. Methylphenidate, a dopamine reuptake blocker, produces moderate addiction-related gene regulation. Findings show that SSRIs such as fluoxetine given in conjunction with methylphenidate potentiate methylphenidate-induced gene regulation in the striatum in rats, consistent with a facilitatory action of serotonin on addiction-related processes. These SSRIs may thus increase methylphenidate's addiction liability. Here, we investigated the effects of a novel SSRI, vilazodone, on methylphenidate-induced gene regulation. Vilazodone differs from prototypical SSRIs in that, in addition to blocking serotonin reuptake, it acts as a partial agonist at the 5-HT1A serotonin receptor subtype. Studies showed that stimulation of the 5-HT1A receptor tempers serotonin input to the striatum. We compared the effects of acute treatment with vilazodone (10-20 mg/kg) with those of fluoxetine (5 mg/kg) on striatal gene regulation (zif268, substance P, enkephalin) induced by methylphenidate (5 mg/kg), by in situ hybridization histochemistry combined with autoradiography. We also assessed the impact of blocking 5-HT1A receptors by the selective antagonist WAY-100635 (0.5 mg/kg) on these responses. Behavioral effects of these drug treatments were examined in parallel in an open-field test. Our results show that, in contrast to fluoxetine, vilazodone did not potentiate gene regulation induced by methylphenidate in the striatum, while vilazodone enhanced methylphenidate-induced locomotor activity. However, blocking 5-HT1A receptors by WAY-100635 unmasked a potentiating effect of vilazodone on methylphenidate-induced gene regulation, thus confirming an inhibitory role for 5-HT1A receptors. Our findings suggest that vilazodone may serve as an adjunct SSRI with diminished addiction facilitating properties and identify the 5-HT1A receptor as a potential therapeutic target to treat addiction.
Identifiants
pubmed: 37807008
doi: 10.1007/s12035-023-03688-y
pii: 10.1007/s12035-023-03688-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDA NIH HHS
ID : DA046794
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Iversen L (2006) Neurotransmitter transporters and their impact on the development of psychopharmacology. Br J Pharmacol 147(Suppl 1):S82–88
pubmed: 16402124
pmcid: 1760736
Castle L, Aubert RE, Verbrugge RR, Khalid M, Epstein RS (2007) Trends in medication treatment for ADHD. J Atten Disord 10:335–342
pubmed: 17449832
Kollins SH (2008) ADHD, substance use disorders, and psychostimulant treatment: current literature and treatment guidelines. J Atten Disord 12:115–125
pubmed: 18192623
Swanson JM, Wigal TL, Volkow ND (2011) 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 137:742–748
pubmed: 21859175
pmcid: 3187625
DSMMD (2000) Diagnostic and statistical Manual of Mental Disorders, Fourth Edition. American Psychiatric Association, Washington, DC
SAMHSA (2015) Behavioral Health Trends in the United States: results from the 2014 National Survey on Drug Use and Health. NSDUH Series H-50, HHS Publication No (SMA) 15–4927 https://www.samhsa.gov/data/sites/default/files/NSDUH-FRR1-2014/NSDUH-FRR1-2014.pdf
Benson K, Flory K, Humphreys KL, Lee SS (2015) Misuse of stimulant medication among college students: a comprehensive review and meta-analysis. Clin Child Fam Psychol Rev 18:50–76
pubmed: 25575768
Compton WM, Han B, Blanco C, Johnson K, Jones CM (2018) Prevalence and correlates of prescription stimulant use, misuse, use disorders, and motivations for misuse among adults in the United States. Am J Psychiatry 175:741–755
pubmed: 29656665
pmcid: 6070393
Carlezon WAJ, Konradi C (2004) Understanding the neurobiological consequences of early exposure to psychotropic drugs: linking behavior with molecules. Neuropharmacology 47:47–60
pubmed: 15464125
pmcid: 4204484
Carrey N, Wilkinson M (2011) A review of psychostimulant-induced neuroadaptation in developing animals. Neurosci Bull 27:197–214
pubmed: 21614102
pmcid: 5560359
Marco EM, Adriani W, Ruocco LA, Canese R, Sadile AG, Laviola G (2011) Neurobehavioral adaptations to methylphenidate: the issue of early adolescent exposure. Neurosci Biobehav Rev 35:1722–1739
pubmed: 21376076
Van Waes V, Steiner H (2015) Fluoxetine and other SSRI antidepressants potentiate addiction-related gene regulation by psychostimulant medications. In: Pinna G (ed) Fluoxetine: Pharmacology, Mechanisms of Action and Potential Side Effects. Nova Science Publishers, Hauppauge, NY, pp 207–225
Rushton JL, Whitmire JT (2001) Pediatric stimulant and selective serotonin reuptake inhibitor prescription trends: 1992 to 1998. Arch Pediatr Adolesc Med 155:560–565
pubmed: 11343498
Safer DJ, Zito JM, DosReis S (2003) Concomitant psychotropic medication for youths. Am J Psychiatry 160:438–449
pubmed: 12611822
Waxmonsky J (2003) Assessment and treatment of attention deficit hyperactivity disorder in children with comorbid psychiatric illness. Curr Opin Pediatr 15:476–482
pubmed: 14508296
Spencer TJ (2006) ADHD and comorbidity in childhood. J Clin Psychiatry 67 Suppl 8:27–31
Lavretsky H, Kim MD, Kumar A, Reynolds CF (2003) Combined treatment with methylphenidate and citalopram for accelerated response in the elderly: an open trial. J Clin Psychiatry 64:1410–1414
pubmed: 14728100
Nelson JC (2007) Augmentation strategies in the treatment of major depressive disorder. Recent findings and current status of augmentation strategies. CNS Spectr 12 Suppl 22:6–9
Ishii M, Tatsuzawa Y, Yoshino A, Nomura S (2008) Serotonin syndrome induced by augmentation of SSRI with methylphenidate. Psychiatry Clin Neurosci 62:246
pubmed: 18412855
Ravindran AV, Kennedy SH, O’Donovan MC, Fallu A, Camacho F, Binder CE (2008) Osmotic-release oral system methylphenidate augmentation of antidepressant monotherapy in major depressive disorder: results of a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry 69:87–94
pubmed: 18312042
Csoka A, Bahrick A, Mehtonen OP (2008) Persistent sexual dysfunction after discontinuation of selective serotonin reuptake inhibitors. J Sex Med 5:227–233
pubmed: 18173768
Volkow ND, Wang GJ, Fowler JS, Logan J, Franceschi D, Maynard L, Ding YS, Gatley SJ, Gifford A, Zhu W, Swanson JM (2002) Relationship between blockade of dopamine transporters by oral methylphenidate and the increases in extracellular dopamine: therapeutic implications. Synapse 43:181–187
pubmed: 11793423
Yano M, Steiner H (2007) Methylphenidate and cocaine: the same effects on gene regulation? Trends Pharmacol Sci 28:588–596
pubmed: 17963850
Pan D, Gatley SJ, Dewey SL, Chen R, Alexoff DA, Ding YS, Fowler JS (1994) Binding of bromine-substituted analogs of methylphenidate to monoamine transporters. Eur J Neurosci 264:177–182
Kuczenski R, Segal DS (1997) Effects of methylphenidate on extracellular dopamine, serotonin, and norepinephrine: comparison with amphetamine. J Neurochem 68:2032–2037
pubmed: 9109529
Segal DS, Kuczenski R (1999) Escalating dose-binge treatment with methylphenidate: role of serotonin in the emergent behavioral profile. J Pharmacol Exp Ther 291:19–30
pubmed: 10490882
Berke JD, Paletzki RF, Aronson GJ, Hyman SE, Gerfen CR (1998) A complex program of striatal gene expression induced by dopaminergic stimulation. J Neurosci 18:5301–5310
pubmed: 9651213
pmcid: 6793476
Yuferov V, Kroslak T, Laforge KS, Zhou Y, Ho A, Kreek MJ (2003) Differential gene expression in the rat caudate putamen after binge cocaine administration: advantage of triplicate microarray analysis. Synapse 48:157–169
pubmed: 12687634
Yuferov V, Nielsen D, Butelman E, Kreek MJ (2005) Microarray studies of psychostimulant-induced changes in gene expression. Addict Biol 10:101–118
pubmed: 15849024
Black YD, Maclaren FR, Naydenov AV, Carlezon WAJ, Baxter MG, Konradi C (2006) Altered attention and prefrontal cortex gene expression in rats after binge-like exposure to cocaine during adolescence. J Neurosci 26:9656–9665
pubmed: 16988036
pmcid: 4203339
Heiman M, Schaefer A, Gong S, Peterson JD, Day M, Ramsey KE, Suárez-Fariñas M, Schwarz C, Stephan DA, Surmeier DJ, Greengard P, Heintz N (2008) A translational profiling approach for the molecular characterization of CNS cell types. Cell 135:738–748
pubmed: 19013281
pmcid: 2696821
Nestler EJ (2014) Epigenetic mechanisms of drug addiction. Neuropharmacology 76, part B:259–268
Steiner H, Van Waes V (2013) Addiction-related gene regulation: risks of exposure to cognitive enhancers vs. other psychostimulants. Prog Neurobiol 100:60–80
pubmed: 23085425
Thanos PK, Michaelides M, Benveniste H, Wang GJ, Volkow ND (2007) Effects of chronic oral methylphenidate on cocaine self-administration and striatal dopamine D2 receptors in rodents. Pharmacol Biochem Behav 87:426–433
pubmed: 17599397
Robison LS, Ananth M, Hadjiargyrou M, Komatsu DE, Thanos PK (2017) Chronic oral methylphenidate treatment reversibly increases striatal dopamine transporter and dopamine type 1 receptor binding in rats. J Neural Transm 124:655–667
pubmed: 28116523
Yano M, Beverley JA, Steiner H (2006) Inhibition of methylphenidate-induced gene expression in the striatum by local blockade of D1 dopamine receptors: interhemispheric effects. Neuroscience 140:699–709
pubmed: 16549270
Alburges ME, Hoonakker AJ, Horner KA, Fleckenstein AE, Hanson GR (2011) Methylphenidate alters basal ganglia neurotensin systems through dopaminergic mechanisms: a comparison with cocaine treatment. J Neurochem 117:470–478
pubmed: 21323925
Bhat RV, Baraban JM (1993) Activation of transcription factor genes in striatum by cocaine: role of both serotonin and dopamine systems. J Pharmacol Exp Ther 267:496–505
pubmed: 8229780
Lucas JJ, Segu L, Hen R (1997) 5-Hydroxytryptamine1B receptors modulate the effect of cocaine on c-fos expression: converging evidence using 5-hydroxytryptamine1B knockout mice and the 5-hydroxytryptamine1B/1D antagonist GR127935. Mol Pharmacol 51:755–763
pubmed: 9145913
Castanon N, Scearce-Levie K, Lucas JJ, Rocha B, Hen R (2000) Modulation of the effects of cocaine by 5-HT1B receptors: a comparison of knockouts and antagonists. Pharmacol Biochem Behav 67:559–566
pubmed: 11164086
Morris BJ, Reimer S, Hollt V, Herz A (1988) Regulation of striatal prodynorphin mRNA levels by the raphe-striatal pathway. Brain Res 464:15–22
pubmed: 3179742
Walker PD, Capodilupo JG, Wolf WA, Carlock LR (1996) Preprotachykinin and preproenkephalin mRNA expression within striatal subregions in response to altered serotonin transmission. Brain Res 732:25–35
pubmed: 8891265
Horner KA, Adams DH, Hanson GR, Keefe KA (2005) Blockade of stimulant-induced preprodynorphin mRNA expression in the striatal matrix by serotonin depletion. Neuroscience 131:67–77
pubmed: 15680692
Van Waes V, Beverley J, Marinelli M, Steiner H (2010) Selective serotonin reuptake inhibitor antidepressants potentiate methylphenidate (Ritalin)-induced gene regulation in the adolescent striatum. Eur J Neurosci 32:435–447
pubmed: 20704593
pmcid: 2921647
Thanos PK, Robison LS, Steier J, Hwang YF, Cooper T, Swanson JM, Komatsu DE, Hadjiargyrou M, Volkow ND (2015) A pharmacokinetic model of oral methylphenidate in the rat and effects on behavior. Pharmacol Biochem Behav 131:143–153
pubmed: 25641666
pmcid: 4461871
Moon C, Marion M, Thanos PK, Steiner H (2021) Fluoxetine potentiates oral methylphenidate-induced gene regulation in the rat striatum. Mol Neurobiol 58:4856–4870
pubmed: 34213723
pmcid: 8500935
Thanos PK, McCarthy M, Senior D, Watts S, Connor C, Hammond N, Blum K, Hadjiargyrou M, Komatsu D, Steiner H (2023) Combined chronic oral methylphenidate and fluoxetine treatment during adolescence: Effects on behavior. Curr Pharm Biotechnol 24:1307–1314
pubmed: 36306463
Senior D, McCarthy M, Ahmed R, Klein S, Lee WX, Hadjiargyrou M, Komatsu D, Steiner H, Thanos PK (2023) Chronic oral methylphenidate plus fluoxetine treatment in adolescent rats increases cocaine self-administration. Addict Neurosci 8:100127
Lamoureux L, Beverley JA, Marinelli M, Steiner H (2023) Fluoxetine potentiates methylphenidate-induced behavioral responses: enhanced locomotion or stereotypies and facilitated acquisition of cocaine self-administration. Addict Neurosci 9:100131
Steiner H, Warren BL, Van Waes V, Bolaños-Guzmán CA (2014) Life-long consequences of juvenile exposure to psychotropic drugs on brain and behavior. Prog Brain Res 211:13–30
pubmed: 24968775
pmcid: 4331026
Alter D, Beverley JA, Patel R, Bolaños-Guzmán CA, Steiner H (2017) The 5-HT1B serotonin receptor regulates methylphenidate-induced gene expression in the striatum: Differential effects on immediate-early genes. J Psychopharmacol 31:1078–1087
pubmed: 28720013
pmcid: 5540766
Borycz J, Zapata A, Quiroz C, Volkow ND, Ferré S (2008) 5-HT(1B) receptor-mediated serotoninergic modulation of methylphenidate-induced locomotor activation in rats. Neuropsychopharmacology 33:619–626
pubmed: 17487226
Van Waes V, Ehrlich S, Beverley JA, Steiner H (2015) Fluoxetine potentiation of methylphenidate-induced gene regulation in striatal output pathways: potential role for 5-HT1B receptor. Neuropharmacology 89:77–86
pubmed: 25218038
Meadows SM, Conti MM, Gross L, Chambers NE, Avnor Y, Ostock CY, Lanza K, Bishop C (2018) Diverse serotonin actions of Vilazodone reduce L-3,4‐dihydroxyphenylalanine-induced dyskinesia in hemi‐parkinsonian rats. Mov Disord 33:1740–1749
pubmed: 30485908
Altwal F, Moon C, West AR, Steiner H (2020) The multimodal serotonergic agent vilazodone inhibits L-DOPA-induced gene regulation in striatal projection neurons and associated dyskinesia in an animal model of Parkinson’s disease. Cells 9:2265
pubmed: 33050305
pmcid: 7600385
Hughes ZA, Starr KR, Langmead CJ, Hill M, Bartoszyk GD, Hagan JJ, Middlemiss DN, Dawson LA (2005) Neurochemical evaluation of the novel 5-HT1A receptor partial agonist/serotonin reuptake inhibitor, vilazodone. Eur J Pharmacol 510:49–57
pubmed: 15740724
Owen RT (2011) Vilazodone: a new treatment option for major depressive disorder. Drugs Today (Barc) 47:531–537
pubmed: 22013560
Cruz MP (2012) Vilazodone HCl (Viibryd): a serotonin partial agonist and reuptake inhibitor for the treatment of major depressive disorder. Pharm Ther 37:28–31
Altwal F, Padovan-Neto FE, Ritger A, Steiner H, West AR (2021) Role of 5-HT1A receptor in vilazodone-mediated suppression of L-DOPA-induced dyskinesia and increased responsiveness to cortical input in striatal medium spiny neurons in an animal model of Parkinson’s disease. Molecules 26:5790
pubmed: 34641332
pmcid: 8510243
Van Waes V, Carr B, Beverley JA, Steiner H (2012) Fluoxetine potentiation of methylphenidate-induced neuropeptide expression in the striatum occurs selectively in direct pathway (striatonigral) neurons. J Neurochem 122:1054–1064
pubmed: 22738672
pmcid: 3423503
Willuhn I, Sun W, Steiner H (2003) Topography of cocaine-induced gene regulation in the rat striatum: relationship to cortical inputs and role of behavioural context. Eur J Neurosci 17:1053–1066
pubmed: 12653981
Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic Press, New York
Yano M, Steiner H (2005) Methylphenidate (ritalin) induces Homer 1a and zif 268 expression in specific corticostriatal circuits. Neuroscience 132:855–865
pubmed: 15837145
Van Waes V, Vandrevala M, Beverley J, Steiner H (2014) Selective serotonin re-uptake inhibitors potentiate gene blunting induced by repeated methylphenidate treatment: Zif268 versus Homer1a. Addict Biol 19:986–995
pubmed: 23763573
Sahli ZT, Banerjee P, Tarazi FI (2016) The preclinical and clinical effects of vilazodone for the treatment of major depressive disorder. Expert Opin Drug Discov 11:515–523
pubmed: 26971593
pmcid: 4841022
Carta M, Carlsson T, Kirik D, Björklund A (2007) Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia in parkinsonian rats. Brain 130:1819–1833
pubmed: 17452372
Nishijima H, Tomiyama M (2016) What mechanisms are responsible for the reuptake of levodopa-derived dopamine in Parkinsonian. Striatum? Front Neurosci 10:575
pubmed: 28018168
Carta M, Björklund A (2018) The serotonergic system in L-DOPA-induced dyskinesia: pre-clinical evidence and clinical perspective. J Neural Transm 125:1195–1202
pubmed: 29480391
Cenci MA (2017) Molecular mechanisms of L-DOPA-induced dyskinesia. In: Steiner H, Tseng KY (eds) Handbook of basal ganglia structure and function. Elsevier, London, pp 857–871
Spigolon G, Fisone G (2018) Signal transduction in L-DOPA-induced dyskinesia: from receptor sensitization to abnormal gene expression. J Neural Transm 125:1171–1186
pubmed: 29396608
Lanza K, Bishop C (2018) Serotonergic targets for the treatment of L-DOPA-induced dyskinesia. J Neural Transm 125:1203–1216
pubmed: 29305656
Cohen SR, Terry ML, Coyle M, Wheelis E, Centner A, Smith S, Glinski J, Lipari N, Budrow C, Manfredsson FP, Bishop C (2022) The multimodal serotonin compound vilazodone alone, but not combined with the glutamate antagonist amantadine, reduces l-DOPA-induced dyskinesia in hemiparkinsonian rats. Pharmacol Biochem Behav 217:173393
pubmed: 35513119
Sellnow RC, Newman JH, Chambers N, West AR, Steece-Collier K, Sandoval IM, Benskey MJ, Bishop C, Manfredsson FP (2019) Regulation of dopamine neurotransmission from serotonergic neurons by ectopic expression of the dopamine D2 autoreceptor blocks levodopa-induced dyskinesia. Acta Neuropathol Commun 7:8
pubmed: 30646956
pmcid: 6332643
Barnes NM, Sharp T (1999) A review of central 5-HT receptors and their function. Neuropharmacology 38:1083–1152
pubmed: 10462127
De Deurwaerdère P, Di Giovanni G (2016) Serotonergic modulation of the activity of mesencephalic dopaminergic systems: therapeutic implications. Prog Neurobiol in press
Budrow C, Elder K, Coyle M, Centner A, Lipari N, Cohen S, Glinski J, Kinzonzi N, Wheelis E, McManus G, Manfredsson F, Bishop C (2023) Serotonergic actions of vortioxetine as a promising avenue for the treatment of L-DOPA-induced dyskinesia. Cells 12:837
pubmed: 36980178
pmcid: 10047495
Lobo MK, Nestler EJ (2011) The striatal balancing act in drug addiction: distinct roles of direct and indirect pathway medium spiny neurons. Front Neuroanat 5:41
pubmed: 21811439
pmcid: 3140647
Steiner H (2017) Psychostimulant-induced gene regulation in striatal circuits. In: Steiner H, Tseng KY (eds) Handbook of Basal Ganglia Structure and Function. Academic Press/Elsevier, London, pp 639–672