Advertisement

Psychopharmacology

, Volume 236, Issue 11, pp 3125–3133 | Cite as

Synergistic anticataleptic effect of imipramine and nicotine in a rotenone-induced rat model

  • Ilya D. IonovEmail author
  • Irina I. Pushinskaya
  • Nicholas P. Gorev
  • Larissa A. Shpilevaya
Original Investigation

Abstract

Rationale

Some antidepressants have been previously found to produce anti-parkinsonian effect; nicotine was known to mitigate experimental neurotoxic lesions. The anticataleptic efficacy of antidepressant-nicotine co-administration is unstudied.

Objectives

This work aimed to evaluate anticataleptic action of imipramine-nicotine combination in rotenone model.

Methods

Catalepsy was measured by the bar test. Concentrations of tyrosine hydroxylase, dopamine, and DOPAC were determined in the substantia nigra and dorsal striatum using ELISA and HPLC techniques; additionally, dopamine/DOPAC ratio was calculated for both areas.

Results

Imipramine and nicotine alone were ineffective; however, co-administration of the drugs significantly (p < 0.01) inhibited rotenone-induced catalepsy and mitigated neurochemical changes in the nigrostriatal system. Anticataleptic effect of the combination exceeded that of levodopa, a standard drug for anti-parkinsonian treatment.

Conclusion

The combined use of imipramine and nicotine at relatively low doses inhibits neurotoxin-induced catalepsy and nigrostriatal neurochemical changes. The co-administration of these drugs might be a new approach to the treatment of extrapyramidal dysfunctions.

Keywords

Imipramine Nicotine Catalepsy Rotenone Dopamine Tyrosine hydroxylase Synergy 

Notes

Acknowledgments

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. I.D.I. is indebted to his long-standing mentors, Prof. Igor Efimovich Kovalev and Prof. Lev Aramovich Piruzyan. The study was supported by the Ministry of Science and Higher Education of the Russian Federation (project АААА-А18-118012390247-0).

Compliance with ethical standards

All experimental animal procedures were conducted according to the European Communities Council Directive 2010/63/EU and approved by the local Ethics Committee for Animal Experimentation.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Alam M, Mayerhofer A, Schmidt WJ (2004) The neurobehavioral changes induced by bilateral rotenone lesion in medial forebrain bundle of rats are reversed by L-DOPA. Behav Brain Res 151:117–124PubMedGoogle Scholar
  2. Al-Khatib IM, Fujiwara M, Ueki S (1989) Relative importance of the dopaminergic system in haloperidol-catalepsy and the anticataleptic effect of antidepressants and methamphetamine in rats. Pharmacol Biochem Behav 33:93–97PubMedGoogle Scholar
  3. Ascherio A, Schwarzschild MA (2016) The epidemiology of Parkinson’s disease: risk factors and prevention. Lancet Neurol 15:1257–1272PubMedGoogle Scholar
  4. Augustine RA, Kokay IC, Andrews ZB, Ladyman SR, Grattan DR (2003) Quantitation of prolactin receptor mRNA in the maternal rat brain during pregnancy and lactation. J Mol Endocrinol 31:221–232PubMedGoogle Scholar
  5. Bertolucci PH, Andrade LA, Lima JG, Carlini EA (1987) Total sleep deprivation and Parkinson disease. Arq Neuropsiquiatr 45:224–230PubMedGoogle Scholar
  6. Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 3:1301–1306PubMedGoogle Scholar
  7. Blesa J, Phani S, Jackson-Lewis V, Przedborski S (2012) Classic and new animal models of Parkinson’s disease. J Biomed Biotechnol 2012:845618PubMedPubMedCentralGoogle Scholar
  8. Capote HA, Rainka M, Westphal ES, Beecher J, Gengo FM (2018) Ropinirole in bipolar disorder: rate of manic switching and change in disease severity. Perspect Psychiatr Care 54(2):100–106PubMedGoogle Scholar
  9. Church WH, Sabol KE, Justice JB Jr, Neill DB (1986) Striatal dopamine activity and unilateral barpressing in rats. Pharmacol Biochem Behav 25:865–871PubMedGoogle Scholar
  10. Costa G, Abin-Carriquiry JA, Dajas F (2001) Nicotine prevents striatal dopamine loss produced by 6-hydroxydopamine lesion in the substantia nigra. Brain Res 888:336–342PubMedGoogle Scholar
  11. Cotzias GC, Papavasiliou PS, Gellene R (1969) Modification of parkinsonism—chronic treatment with L-dopa. New Engl J Med 280:337–345PubMedGoogle Scholar
  12. Denmark JC, David JD, McComb SG (1961) Imipramine hydrochloride (Tofranil) in parkinsonism. A preliminary report. Br J Clin Pract 15:523–524PubMedGoogle Scholar
  13. Dijk S, Krugers HJ, Korf J (1991) The effect of theophylline and immobilization stress on haloperidol-induced catalepsy and on metabolism in the striatum and hippocampus, studied with lactography. Neuropharmacology 30:469–473PubMedGoogle Scholar
  14. Dilsauer SC, Hariharen M, Davidson RK (1988) Desipramine subsensitizes nicotinic mechanism involved in regulating core temperature. Psychiatry Res 25:105–108PubMedGoogle Scholar
  15. Duncan GE, Knapp DJ, Carson SW, Breese GR (1998) Differential effects of chronic antidepressant treatment on swim stress- and fluoxetine-induced secretion of corticosterone and progesterone. J Pharmacol Exp Ther 285:579–587PubMedPubMedCentralGoogle Scholar
  16. Erzin-Waters C, Muller P, Seeman P (1976) Catalepsy induced by morphine or haloperidol: effects of apomorphine and anticholinergic drugs. Can J Physiol Pharmacol 54:516–519PubMedGoogle Scholar
  17. Gillhespy RO, Mustard DM (1963) The evaluation of imipramine in the treatment of Parkinson’s disease. Br J Clin Pract 17:205–208PubMedGoogle Scholar
  18. Goetz CG, Tanner CM, Klawans HL (1984) Bupropion in Parkinson’s disease. Neurology 34:1092–1094PubMedGoogle Scholar
  19. Hart A (2001) Mann-Whitney test is not just a test of medians: differences in spread can be important. Br Med J 323(7309):391–393Google Scholar
  20. Hefti F, Enz A, Melamed E (1985) Partial lesions of the nigrostriatal pathway in the rat. Acceleration of transmitter synthesis and release of surviving dopaminergic neurones by drugs. Neuropharmacology 24:19–23PubMedGoogle Scholar
  21. Hefti F, Melamed E, Wurtman RJ (1980) Partial lesions of the dopaminergic nigrostriatal system in rat brain: biochemical characterization. Brain Res 195:123–137PubMedGoogle Scholar
  22. Hermann B, Pulver R (1960) Der Stoffwechsel des Psychopharmakons Tofranil. Arch Int Pharmacodyn Thér 126:454–469Google Scholar
  23. Holma IA, Holma KM, Melartin TK, Ketokivi M, Isometsä ET (2013) Depression and smoking: a 5-year prospective study of patients with major depressive disorder. Depress Anxiety 30:580–588PubMedGoogle Scholar
  24. Hornykiewicz O (1998) Biochemical aspects of Parkinson’s disease. Neurology 51(2 Suppl 2):S2–S9PubMedGoogle Scholar
  25. Högl B, Peralta C, Wetter TC, Gershanik O, Trenkwalder C (2001) Effect of sleep deprivation on motor performance in patients with Parkinson’s disease. Mov Disord 16:616–621PubMedGoogle Scholar
  26. Hsieh PF, Chia L, Ni D, Cheng L, Ho Y, Tzeng S, Chang M, Hong J (2002) Behavior, neurochemistry and histology after intranigral lipopolysaccharide injection. Neuroreport 13:277–280PubMedGoogle Scholar
  27. Ionov ID, Pushinskaya II, Gorev NP (2018) Cyclosomatostatin-induced catalepsy in the aged rat: a response to levodopa, diphenhydramine and nicotine. Curr Topics Pharmacol 22:45–54Google Scholar
  28. Kalia LV, Lang AE (2015) Parkinson’s disease. Lancet 386(9996):896–912PubMedGoogle Scholar
  29. Kataoka Y, Ohta H, Fujiwara M, Oishi R, Ueki S (1987) Noradrenergic involvement in catalepsy induced by delta 9-tetrahydrocannabinol. Neuropharmacology 26:55–60PubMedGoogle Scholar
  30. Kheradmand A, Nayebi AM, Jorjani M, Haddadi R (2016) Effect of WR-1065 on 6-hydroxydopamine-induced catalepsy and IL-6 level in rats. Iran J Basic Med Sci 19:490–496PubMedPubMedCentralGoogle Scholar
  31. Kleiber AC, Zheng H, Schultz HD, Peuler JD, Patel KP (2008) Exercise training normalizes enhanced glutamate-mediated sympathetic activation from the PVN in heart failure. Am J Phys Regul Integr Comp Phys 294:R1863–R1872Google Scholar
  32. Laitinen L (1969) Desipramine in treatment of Parkinson’s disease. A placebo-controlled study. Acta Neurol Scand 45:109–113PubMedGoogle Scholar
  33. Lavielle S, Tassin JP, Thierry AM, Blanc G, Herve D, Barthelemy C, Glowinski J (1979) Blockade by benzodiazepines of the selective high increase in dopamineturnover induced by stress in mesocortical dopaminergic neurons of the rat. Brain Res 168:585–594PubMedGoogle Scholar
  34. Li X, Li W, Liu G, Shen X, Tang Y (2015) Association between cigarette smoking and Parkinson’s disease: a meta-analysis. Arch Gerontol Geriatr 61:510–516PubMedGoogle Scholar
  35. Liang T, Habegger K, Spence JP, Foroud T, Ellison JA, Lumeng L, Li TK, Carr LG (2004) Glutathione S-transferase 8-8 expression is lower in alcohol-preferring than in alcohol-nonpreferring rats. Alcohol Clin Exp Res 28:1622–1628PubMedPubMedCentralGoogle Scholar
  36. Mandell AJ, Markham C, Fowler W (1961) Parkinson’s syndrome, depression and imipramine. A preliminary report. Calif Med 95:12–14PubMedPubMedCentralGoogle Scholar
  37. Onodera K (1991) Effects of antidepressants and antihistaminics on catalepsy induced by intracerebroventricular administration of histamine in mice. Methods Find Exp Clin Pharmacol 13:397–403PubMedGoogle Scholar
  38. Palkovits M (1973) Isolated removal of hypothalamic or other brain nuclei of the rat. Brain Res 59:449–450PubMedGoogle Scholar
  39. Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic Press, San DiegoGoogle Scholar
  40. Pflug B, Tölle R (1971) Therapie endogener Depressionen durch Schlafentzug. Nervenarzt 42:117–124PubMedGoogle Scholar
  41. Popik P, Kozela E, Krawczyk M (2003) Nicotine and nicotinic receptor antagonists potentiate the antidepressant-like effects of imipramine and citalopram. Br J Pharmacol 139:1196–1202PubMedPubMedCentralGoogle Scholar
  42. Rampello L, Chiechio S, Raffaele R, Vecchio I, Nicoletti F (2002) The SSRI, citalopram, improves bradykinesia in patients with Parkinson’s disease treated with L-dopa. Clin Neuropharmacol 25:21–24PubMedGoogle Scholar
  43. Reist C, Sokolski KN, Chen CC, Coskinas E, Demet EM (1995) The effect of sleep deprivation on motor impairment and retinal adaptation in Parkinson’s disease. Prog Neuro-Psychopharmacol Biol Psychiatry 19:445–454Google Scholar
  44. Ryan RE, Ross SA, Drago J, Loiacono RE (2001) Dose-related neuroprotective effects of chronic nicotine in 6-hydroxydopamine treated rats, and loss of neuroprotection in alpha4 nicotinic receptor subunit knockout mice. Br J Pharmacol 132:1650–1656PubMedPubMedCentralGoogle Scholar
  45. Sanberg PR, Pisa M, Fibiger HC (1981) Kainic acid injections in the striatum alter the cataleptic and locomotor effects of drugs influencing dopaminergic and cholinergic systems. Eur J Pharmacol 74:347–357PubMedGoogle Scholar
  46. Schulte W (1966) Kombinierte Psycho- und Pharmakotherapie bei Melancholikern. In: Kranz H, Petrilowitsch N (eds) Probleme der pharmakopsychiatrischen Kombinations- und Langzeitbehandlung. Karger, Basel, pp 150–169Google Scholar
  47. Sigwald J, Bouttier D, Marques M, Basset J, Gal JC (1959) Amélioration de l’akinésie parkinsonienne par deux derives de l’iminodibenzyle. Rev Neurol (Paris) 101:583–584Google Scholar
  48. Soto-Otero R, Méndez-Alvarez E, Hermida-Ameijeiras A, López-Real AM, Labandeira-García JL (2002) Effects of (-)-nicotine and (-)-cotinine on 6-hydroxydopamine-induced oxidative stress and neurotoxicity: relevance for Parkinson’s disease. Biochem Pharmacol 64:125–135PubMedGoogle Scholar
  49. Strang RR (1965) Imipramine in treatment of parkinsonism: a double-blind placebo study. Br Med J 2:33–34PubMedPubMedCentralGoogle Scholar
  50. Tang SP, Kuttulebbai Nainamohamed Salam S, Jaafar H, Gan SH, Muzaimi M, Sulaiman SA (2017) Tualang honey protects the rat midbrain and lung against repeated paraquat exposure. Oxidative Med Cell Longev 2017:4605782.  https://doi.org/10.1155/2017/4605782 CrossRefGoogle Scholar
  51. Tatara A, Shimizu S, Shin N, Sato M, Sugiuchi T, Imaki J, Ohno Y (2012) Modulation of antipsychotic-induced extrapyramidal side effects by medications for mood disorders. Prog Neuro-Psychopharmacol Biol Psychiatry 38:252–259Google Scholar
  52. Tikhonova MA, Alperina EL, Tolstikova TG, Bazovkina DV, Di VY, Idova GV, Kulikov AV, Popova NK (2010) Effects of chronic fluoxetine treatment on catalepsy and the immune response in mice with a genetic predisposition to freezing reactions: the roles of types 1A and 2A serotonin receptors and the tph2 and SERT genes. Neurosci Behav Physiol 40:521–527PubMedGoogle Scholar
  53. Tretiakoff C (1919) Contribution a l’étude de l’Anatomie pathologique du Locus Niger de Soemmering avec quelques déductions relatives à la pathogenie des troubles du tonus musculaire et de la maladie de Parkinson (Thèse de Doctorat). Université de Paris, ParisGoogle Scholar
  54. Visanji NP, O'Neill MJ, Duty S (2006) Nicotine, but neither the alpha4beta2 ligand RJR2403 nor an alpha7 nAChR subtype selective agonist, protects against a partial 6-hydroxydopamine lesion of the rat median forebrain bundle. Neuropharmacology 51:506–516PubMedGoogle Scholar
  55. Yang Y, Liu X, Long Y, Wang F, Ding JH, Liu SY, Sun YH, Yao HH, Wang H, Wu J, Hu G (2006) Activation of mitochondrial ATP-sensitive potassium channels improves rotenone-related motor and neurochemical alterations in rats. Int J Neuropsychopharmacol 9:51–61PubMedGoogle Scholar
  56. Zetler G (1968) Cataleptic state and hypothermia in mice, caused by central cholinergic stimulation and antagonized by anticholinergic and antidepressant drugs. Int J Neuropharmacol 7:325–335PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Centre on Theoretical Problems in Physical and Chemical PharmacologyRussian Academy of SciencesMoscowRussia
  2. 2.Timpharm LTDMoscowRussia

Personalised recommendations