Pramipexole at a Low Dose Induces Beneficial Effect in the Harmaline-induced Model of Essential Tremor in Rats

CNS Neurosci Ther. 2016 Jan;22(1):53-62. doi: 10.1111/cns.12467. Epub 2015 Oct 13.

Abstract

Aims: The aim of the study was to examine the effects of preferential agonists of dopamine D3 receptors: pramipexole and 7-OH-DPAT on the harmaline-induced tremor in rats (a model of essential tremor, ET). To study receptor mechanisms of these drugs, rats were pretreated with dopamine D3 receptor antagonists--SB-277011-A and SR-21502, an antagonist of presynaptic D2/D3 receptors--amisulpride, or a nonselective antagonist of D2-like receptors, haloperidol, at a postsynaptic dose.

Methods: For tremor measurement, fully automated force plate actimeters were used and data were analyzed using fast Fourier transform.

Results: Harmaline (15 mg/kg ip)-triggered tremor was manifested by an increase in the power within 9-15 Hz band (AP2). Pramipexole administered at a low (0.1 mg/kg sc), but not higher doses (0.3 and 1 mg/kg sc), and 7-OH-DPAT (0.1, 0.3, and 1 mg/kg sc) reversed the harmaline-increased AP2. None of the examined dopamine antagonists: SB-277011-A (10 mg/kg ip), SR-21502 (15 mg/kg ip), haloperidol (0.5 mg/kg ip), or amisulpride (1 mg/kg ip) influenced the above effect of dopamine agonists.

Conclusion: The present study indicates that pramipexole reduces the harmaline-induced tremor, which may suggest its beneficial effects in ET patients. However, mechanisms underlying its action are still unclear and need further examination.

Keywords: Cerebellum; Dopamine receptors; Essential tremor; Harmaline-induced tremor; Pramipexole.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amisulpride
  • Animals
  • Anti-Dyskinesia Agents / administration & dosage*
  • Benzothiazoles / administration & dosage*
  • Disease Models, Animal
  • Dopamine Agonists / administration & dosage
  • Dopamine Antagonists / pharmacology
  • Dose-Response Relationship, Drug
  • Essential Tremor / drug therapy*
  • Essential Tremor / physiopathology
  • Haloperidol / pharmacology
  • Harmaline
  • Imidazoles / pharmacology
  • Male
  • Movement / drug effects
  • Nitriles / pharmacology
  • Pramipexole
  • Pyridines / pharmacology
  • Rats, Wistar
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3 / metabolism
  • Sulpiride / analogs & derivatives
  • Sulpiride / pharmacology
  • Tetrahydroisoquinolines / pharmacology
  • Tetrahydronaphthalenes / administration & dosage
  • Treatment Outcome

Substances

  • Anti-Dyskinesia Agents
  • Benzothiazoles
  • DRD2 protein, rat
  • Dopamine Agonists
  • Dopamine Antagonists
  • Drd3 protein, rat
  • Imidazoles
  • Nitriles
  • Pyridines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • SB 277011
  • SR 21502
  • Tetrahydroisoquinolines
  • Tetrahydronaphthalenes
  • Sulpiride
  • Amisulpride
  • Pramipexole
  • Harmaline
  • Haloperidol
  • 7-hydroxy-2-N,N-dipropylaminotetralin