Abstract
Rationale and objective
Whether monoamine oxidase inhibitors (MAOIs) can be used to suppress the reinforcing effect of cocaine remains unknown. This study was undertaken to examine effects of a long-term dosing regimen with selective MAOIs on cocaine and food reward.
Materials and methods
Since single dose of clorgyline (2 mg/kg), deprenyl (1 mg/kg), and pargyline (10 mg/kg) did not acutely affect mouse locomotor activity, these doses were chosen to treat the male C57BL/6j mice on a daily basis.
Results
Fourteen consecutive days of pretreatments with clorgyline, deprenyl, or pargyline (one injection per day) did not affect natural reward-supported operant behavior, since acquisition of the lever pressing responses for food pellets under an FR-1 protocol did not differ among these drug- and saline-treated mice. Likewise, 24 consecutive days of pretreatments with clorgyline did not alter acquisition of the cocaine (0.3 mg/kg per infusion)-supported operant responses under an FR-1 protocol. In contrast, 24 days of pretreatments with deprenyl and pargyline abolished the cocaine-supported operant responses under a similar protocol. Twenty-four days of clorgyline treatment enhanced serotonin contents in striatum, nucleus accumbens, and frontal cortex. Frontal cortical 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacidic acid concentrations were decreased following 24 days of pretreatments with deprenyl and pargyline. These changes were not evident in mice pretreated with clorgyline.
Conclusions
We suggest that long-term treatments with MAO-B inhibitors may decrease cocaine-supported operant responses in cocaine-naïve mice by selectively decreasing frontal cortical metabolism of dopamine and serotonin.
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References
Bartzokis G, Beckson M, Newton T, Mandelkern M, Mintz J, Foster JA, Ling W, Bridge TP (1999) Selegiline effects on cocaine-induced changes in medial temporal lobe metabolism and subjective ratings of euphoria. Neuropsychopharmacology 20:582–590
Bodkin JA, Amsterdam JD (2002) TRansdermal selegiline in major depression: a double-blind, placebo-controlled, parallel-group study in outpatients. Am J Psych 159:1869–1975
Cornelius JR, Salloum IM, Thase ME, Haskett RF, Daley DC, Jones-Barlock A, Upsher C, Perel JM (1998) Fluoxetine versus placebo in depressed alcoholic cocaine abusers. Psychopharmacol Bull 34:117–121
Culver KE, Rosenfeld JM, Szechtman H (2002) Monoamine oxidase inhibitor-induced blockade of locomotor sensitization to quinpirole: role of striatal dopamine uptake inhibition. Neuropharmacology 43:385–393
Davis LL, Rush JA, Wisniewski SR, Rice K, Cassano P, Jewell ME, Biggs MM, Shores-Wilson K, Balasubramani GK, Husain MM, Quitkin FM, McGrath PJ (2005) Substance use disorder comorbidity in major depressive disorder: an exploratory analysis of the Sequenced Treatment Alternatives to Relieve Depression cohort. Compr Psychiatry 46:81–89
Ebadi M, Brown-Borg H, Ren J, Shama S, Shavali S, El ReFaey H, Carlson EC (2006) Therapeutic efficacy of selegiline in neurodegenerative disorders and neurological diseases. Curr Drug Targets 7:1513–1529
Elkashef A, Fudala PJ, Gorgon L, Li SH, Kahn R, Chiang N, Vocci F, Collins J, Jones K, Boardman K, Sather M (2006) Double-blind, placebo-controlled trial of selegiline transdermal system (STS) for the treatment of cocaine dependence. Drug Alcohol Depend 85:191–197
Feldman RS, Meyer JS, Quenzer LF (1997) Principles of neuropsychopharmacology. Sinauer, Sunderland, Massachusetts, USA, p 297
George TP, Weinberger AH (2008) Monoamine oxidase inhibition for tobacco pharmacotherapy. Clin Pharmacol Ther 83:619–621
Harsing LG (2006) The pharmacology of the neurochemical transmission in the midbrain raphe nuclei of the rat. Curr Neuropharmacol 4:313–339
He S, Grasing K (2006) l-Methamphetamine and selective MAO inhibitors decrease morphine-reinforced and non-reinforced behavior in rats; Insights towards selegiline's mechanism of action. Pharmacol Biochem Behav 85:675–688
Houtmuller EJ, Notes LD, Newton T, van Sluis N, Chiang N, Elkashef A, Bigelow GE (2004) Transdermal selegiline and intravenous cocaine: safety and interactions. Psychopharmacology (Berl) 172:31–40
Hurd YL, Herkenham M (1993) Molecular alterations in the neostriatum of human cocaine addicts. Synapse 13:357–369
Lamensdorf I, Youdim MB, Finberg JP (1996) Effect of long-term treatment with selective monoamine oxidase A and B inhibitors on dopamine release from rat striatum in vivo. J Neurochem 67:1532–1539
Lewis A, Miller JH, Lea RA (2007) Monoamine oxidase and tobacco dependence. Neurotoxicology 28:182–195
Little KY, Zhang L, Desmond T, Frey KA, Dalack GW, Cassin BJ (1999) Striatal dopaminergic abnormalities in human cocaine users. Am J Psychiatry 156:238–245
Newton TF, La Garza R 2nd, Fong T, Chiang N, Holmes TH, Bloch DA, Anderson A, Elkashef A (2005) A comprehensive assessment of the safety of intravenous methamphetamine administration during treatment with selegiline. Pharmacol Biochem Behav 82:704–711
Pepper JP, Baumann MH, Ayestas M, Rothman RB (2001) Inhibition of MAO-A fails to alter cocaine-induced increases in extracellular dopamine and norepinephrine in rat nucleus accumbens. Brain Res Mol Brain Res 87:184–189
Philibert RA, Gunter TD, Beach SR, Brody GH, Madan A (2008) MAOA methylation is associated with nicotine and alcohol dependence in women. Am J Med Genet B Neuropsychiatr Genet 147B:565–570
Rothman RB, Blough BE, Woolverton WL, Anderson KG, Negus SS, Mello NK, Roth BL, Baumann MH (2005) Development of a rationally designed, low abuse potential, biogenic amine releaser that suppresses cocaine self-administration. J Pharmacol Exp Ther 313:1361–1369
Rubin E, Aharonovich E, Bisaga A, Levin FR, Raby WN, Nunes EV (2007) Early abstinence in cocaine dependence: influence of comorbid major depression. Am J Addict 16:283–290
Sora I, Hall FS, Andrews AM, Itokawa M, Li XF, Wei HB, Wichems C, Lesch KP, Murphy DL, Uhl GR (2001) Molecular mechanisms of cocaine reward: combined dopamine and serotonin transporter knockouts eliminate cocaine place preference. Proc Natl Acad Sci U S A 98:5300–5305
Villegier AS, Blanc G, Glowinski J, Tassin JP (2003) Transient behavioral sensitization to nicotine becomes long-lasting with monoamine oxidases inhibitors. Pharmacol Biochem Behav 76:267–274
Wilcon KM, Paul IA, Woolverton WL (1999) Comparison between dopamine transporter affinity and self-administration potency of local anesthetics in rhesus monkeys. Eur J Pharm 367:175–181
Wilson JM, Levey AI, Bergeron C, Kalasinsky K, Ang L, Peretti F, Adams VI, Smialek J, Anderson WR, Shannak K, Deck J, Niznik HB, Kish SJ (1996) Striatal dopamine, dopamine transporter, and vesicular monoamine transporter in chronic cocaine users. Ann Neurol 40:428–439
Winger GD, Yasar S, Negus SS, Goldberg SR (1994) Intravenous self-administration studies with l-deprenyl (selegiline) in monkeys. Clin Pharmacol Ther 56:774–780
Acknowledgments
This research is supported by ROC National Science Council grants 952413H006003MY2 and 952320B006042 to L.Y.
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Ho, MC., Cherng, C.G., Tsai, YP.N. et al. Chronic treatment with monoamine oxidase-B inhibitors decreases cocaine reward in mice. Psychopharmacology 205, 141–149 (2009). https://doi.org/10.1007/s00213-009-1524-5
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DOI: https://doi.org/10.1007/s00213-009-1524-5