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Apomorphine enhances harmaline-induced tremor in rats

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Abstract

Background

Harmaline-induced tremor is a well-known model of essential tremor in humans. The aim of the present study was to examine the influence of apomorphine, a non-selective dopamine receptor agonist, on the tremor induced by harmaline in rats. Propranolol (a first-line drug in essential tremor) was used as a reference compound.

Methods

Tremor, locomotor activity and focused stereotypy were measured objectively using force plate actimeters. Tremor was analyzed using a Fourier transform to generate power spectra for rhythmic behavior.

Results

The tremor induced by harmaline administered at a dose of 15 mg/kg ip was associated with an increase in power in the 9–15 Hz band (AP2) and in the tremor index, calculated as a difference between AP2 and power in the 0–8 Hz band (AP1). Propranolol injected at a dose of 20 mg/kg ip reversed both of these effects of harmaline. Apomorphine administered at the doses of 0.5 and 1 mg/kg sc further enhanced AP2 and at the lower dose also the tremor index elevated by harmaline. This increase in AP2 was stronger than enhancement of locomotor activity induced by apomorphine in the harmaline-treated animals.

Conclusions

The present study suggests that the dopamine agonist apomorphine enhances the tremor induced by harmaline, and this effect is at least partly independent of hyperactivity.

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References

  1. Zappia M, Albanese A, Bruno E, Colosimo C, Filippini G, Martinelli P, et al. Treatment of essential tremor; a systematic review of evidence and recommendations from the italian movement disorders association. J Neurol 2013;260(3):714–40.

    Article  PubMed  Google Scholar 

  2. Martin FC, Thu Le A, Handforth A. Harmaline-induced tremor as a potential preclinical screening method for essential tremor medications. Mov Disord 2005;20(3):298–305.

    Article  PubMed  Google Scholar 

  3. Paterson NE, Mallekiani SA, Foireman MM, Olivier B, Hanania T. Pharmacological characterization of harmaline-induced tremor in mice. Eur J Pharmacol 2009;616(1–3):73–80.

    Article  CAS  PubMed  Google Scholar 

  4. Miwa H. Rodent models of tremor. Cerebellum 2007;6(1):66–72.

    Article  CAS  PubMed  Google Scholar 

  5. Zhang N, Walberg F, Laake JH, Meldrum BS, Ottersen OP. Aspartate-like and glutamate-like immunoreactivities in the inferior olive and climbing fibre system: a light microscopic and semiquantitative electron microscopic study in rat and baboon (Papio anubis). Neuroscience 1990;38(1):61–80.

    Article  CAS  PubMed  Google Scholar 

  6. Beitz AJ, Saxon D. Harmaline-induced climbing fiber activation causes amino acid and peptide release in the rodent cerebellar cortex and a unique temporal pattern of Fos expression in the olivo-cerebellar pathway. J Neurocytol 2004;33(1):49–74.

    Article  CAS  PubMed  Google Scholar 

  7. Gołembiowska K, Berghauzen-Maciejewska K, Górska A, Kamińska K, Ossowska K. A partial lesion of the substantia nigra pars compacta and retrorubral field decreases the harmaline-induced glutamate release in the rat cerebellum. Brain Res 2013;1537:303–11.

    Article  PubMed  Google Scholar 

  8. Lamarre Y, De Montigny C, Dumont M, Weiss M. Harmaline-induced rhythmic activity of cerebellar and lower brain stem neurons. Brain Res 1971;32(1):246–50.

    Article  CAS  PubMed  Google Scholar 

  9. Ikai Y, Takada M, Shinonaga Y, Mizuno N. Dopaminergic and non-dopaminergic neurons in the ventral tegmental area of the rat project, respectively, to the cerebellar cortex and deep cerebellar nuclei. Neuroscience 1992;51(3):719–28.

    Article  CAS  PubMed  Google Scholar 

  10. Kizer JS, Palkovits M, Brownstein MJ. The projections of the A8, A9 and A10 dopaminergic cell bodies: evidence for a nigral-hypothalamic-median eminence dopaminergic pathway. Brain Res 1976;108(2):363–70.

    Article  CAS  PubMed  Google Scholar 

  11. Takada M, Sugimoto T, Hattori T. Tyrosine hydroxylase immunoreactivity in cerebellar Purkinje cells of the rat. Neurosci Lett 1993;150(1):61–4.

    Article  CAS  PubMed  Google Scholar 

  12. Kim YS, Shin JH, Hall FS, Linden DJ. Dopamine signaling is required for depolarization-induced slow current in cerebellar Purkinje cells. J Neurosci 2009;29(26):8530–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ishibashi T, Wakabayashi J, Ohno Y. 7-Hydroxy-N,N′-di-n-propyl-2-aminotetraline, a preferential dopamine D3 agonist, induces c-fos mRNA expression in the rat cerebellum. Jpn J Pharmacol 2002;89(3):309–15.

    Article  CAS  PubMed  Google Scholar 

  14. Herrera-Meza G, Aguirre-Manzo L, Coria-Avila GA, Lopez-Meraz ML, Toledo-Cárdenas R, Manzo J, et al. Beyond the basal ganglia: cFos expression in the cerebellum in response to acute and chronic dopaminergic alterations. Neuroscience 2014;267:219–31.

    Article  CAS  PubMed  Google Scholar 

  15. Yang J, Sadler TR, Givrad TK, Maarek J-M, Holschneider DP. Changes in brain functional activation during resting and locomotor states after unilateral damage in rats. NeuroImage 2007;36(3):755–73.

    Article  CAS  PubMed  Google Scholar 

  16. Heman P, Barcia C, Gómez A, Ros CM, Ros-Bernal F, Yuste JE, et al. Nigral degeneration correlates with persistent activation of cerebellar Purkinje cells in MPTP-treated monkeys. Histol Histopathol 2012;27(1):89–94.

    CAS  PubMed  Google Scholar 

  17. Kolasiewicz W, Kuter K, Berghauzen K, Nowak P, Schulze G, Ossowska K. 6-OHDA injections into A8–A9 dopaminergic neurons modelling early stages of Parkinson’s disease increase the harmaline-induced tremor in rats. Brain Res 2012;1477:59–73.

    Article  CAS  PubMed  Google Scholar 

  18. Costall B, Kelly DM, Naylor RJ. The importance of 5-hydroxytryptamine for the induction of harmaline tremor and its antagonism by dopaminergic agonists assessed by lesions of the midbrain raphe nuclei. Eur J Pharmacol 1976;35(1):109–19.

    Article  CAS  PubMed  Google Scholar 

  19. Ossowska K, Wardas J, Berghauzen-Maciejewska K, Głowacka U, Kuter K, Pilc A, et al. a positive allosteric modulator of mGlu4 receptors, reduces the harmaline-induced hyperactivity but not tremor in rats. Neuropharmacology 2014;83:28–35.

    Article  CAS  PubMed  Google Scholar 

  20. Costall B, Naylor RJ. The role of telencephalic dopaminergic systems in the mediation of apomorphine-stereotyped behaviour. Eur J Pharmacol 1972;24(1):8–24.

    Article  Google Scholar 

  21. Maj J, Grabowska M, Gajda L. Effect of apomorphine on motility in rats. Eur J Pharmacol 1972;17(2):208–14.

    Article  CAS  PubMed  Google Scholar 

  22. Ossowska K, We˛dzony K, Wolfarth S. The role of the GABA mechanisms of the globus pallidus in mediating catalepsy, stereotypy and locomotor activity. Pharmacol Biochem Behav 1984;21(6):825–31.

    Article  CAS  PubMed  Google Scholar 

  23. Poli A, Palermo-Neto J. Effects of D,L-propranolol on open field behavior of rats. Psychopharmacology 1985;86(1–2):153–5.

    Article  CAS  PubMed  Google Scholar 

  24. Wang G, Fowler SC. Concurrent quantification of tremor and depression of locomotor activity in rats by harmaline and physostigmine. Psychopharmacology 2001;158(3):273–80.

    Article  CAS  PubMed  Google Scholar 

  25. Fowler SC, Berkestrand BR, Chen R, Moss SJ, Vorotsova E, Wang G, et al. A force-plate actimeter for quantitating rodent behaviors: illustrative data on locomotion, rotation, spatial patterning, stereotypies, and tremor. J Neurosci Methods 2001;107(1–2):107–24.

    Article  CAS  PubMed  Google Scholar 

  26. Fowler SC. Behavioral spectroscopy with the Force-Plate Actometer. Curr Sep 2002;20(1):17–22.

    CAS  Google Scholar 

  27. Fowler SC, Pinkston JW, Vorontsova E. Clozapine and prazosin slow the rhythm of head movements during focused stereotypy induced by d-amphetamine in rats. Psychopharmacology 2007;192(2):219–30.

    Article  CAS  PubMed  Google Scholar 

  28. Katner S, Nikolaidis N, Markham J, Clevenger S. Automated measurement of amphetamine-induced focused stereotypy in rats and harmaline-induced tremor in mice: an introduction to the force plate actimeter. Curr Sep Drug Dev 2007;22(1):18–20.

    CAS  Google Scholar 

  29. Fowler SC, Covington III HE, Miczek KA. Stereotyped and complex motor routines expressed during cocaine self-administration: results from a 24 h binge of unlimited cocaine access in rats. Psychopharmacology 2007;192:465–78.

    Article  CAS  PubMed  Google Scholar 

  30. Barik S, de Baurepaire R. Evidence for a functional role of the dopamine D3 receptors in the cerebellum. Brain Res 1996;737(1–2):347–50.

    Article  CAS  PubMed  Google Scholar 

  31. Barili P, Bronzetti E, Ricci A, Zaccheo D, Amenta F. Microanatomical localization of dopamine receptor protein immunoreactivity in the rat cerebellar cortex. Brain Res 2000;854(1–2):130–8.

    Article  CAS  PubMed  Google Scholar 

  32. Diaz J, Pilon C, Le Foll B, Gross C, Triller A, Schwartz JC, et al. Dopamine D3 receptors expressed by all mesencephalic neurons. J Neurosci 2000;20(23):8677–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kim H, Sablin SO, Ramsay RR. Inhibition of monoamine oxidase A by betacarboline derivatives. Arch Biochem Biophys 1997;337(1):137–42.

    Article  CAS  PubMed  Google Scholar 

  34. Reid MS, Hsu Jr H, Souza KH, Broderick PA, Berger SP. Neuropharmacological characterization of local ibocaine effects on dopamine release. J Neural Transm 1996;103(8–9):967–85.

    Article  CAS  PubMed  Google Scholar 

  35. Iurlo M, Leone G, Schilström B, Linnér L, Nomikos G, Hertel P, et al. Effects of harmine on dopamine output and metabolism in rat striatum: role of monoamine oxidase – a inhibition. Psychopharmacology 2001;159(1):98–104.

    Article  CAS  PubMed  Google Scholar 

  36. Vilela-Filho O, Ferraz FP, Barros BA, Silva LO, Anunciação SF, Souza JT, et al. Effects of unilateral stereotactic posterior striatotomy on harmaline-induced tremor in rats. J Neurosci Res 2013;91(10):1328–37.

    Article  CAS  PubMed  Google Scholar 

  37. Bostan AC, Dum RP, Strick PL. The basal ganglia communicate with the cerebellum. PNAS 2010;107(18):8452–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Parent A, Hazrati L-N. Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Res Rev 1995;20(1):128–54.

    CAS  PubMed  Google Scholar 

  39. Sandvik U, Koskinen LO, Lundquist A, Blomstedt P. Thalamic and subthalamic deep brain stimulation for essential tremor: where is the optimal target? Neurosurgery 2012;70(4):840–5.

    Article  PubMed  Google Scholar 

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Correspondence to Krystyna Ossowska.

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Ossowska, K., Głowacka, U., Kosmowska, B. et al. Apomorphine enhances harmaline-induced tremor in rats. Pharmacol. Rep 67, 435–441 (2015). https://doi.org/10.1016/j.pharep.2014.11.008

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  • DOI: https://doi.org/10.1016/j.pharep.2014.11.008

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