Pramipexole Reduces zif-268 mRNA Expression in Brain Structures involved in the Generation of Harmaline-Induced Tremor.

Abstract

Essential tremor is one of the most common neurological disorders, however, it is not sufficiently controlled with currently available pharmacotherapy. Our recent study has shown that pramipexole, a drug efficient in inhibiting parkinsonian tremor, reduced the harmaline-induced tremor in rats, generally accepted to be a model of essential tremor. The aim of the present study was to investigate brain targets for the tremorolytic effect of pramipexole by determination of the early activity-dependent gene zif-268 mRNA expression. Tremor in rats was induced by harmaline administered at a dose of 15 mg/kg ip. Pramipexole was administered at a low dose of 0.1 mg/kg sc. Tremor was measured by Force Plate Actimeters where four force transducers located below the corners of the plate tracked the animal's position on a Cartesian plane. The zif-268 mRNA expression was analyzed by in situ hybridization in brain slices. Harmaline induced tremor and increased zif-268 mRNA levels in the inferior olive, cerebellar cortex, ventroanterior/ventrolateral thalamic nuclei and motor cortex. Pramipexole reversed both the harmaline-induced tremor and the increase in zif-268 mRNA expression in the inferior olive, cerebellar cortex and motor cortex. Moreover, the tremor intensity correlated positively with zif-268 mRNA expression in the above structures. The present results seem to suggest that the tremorolytic effect of pramipexole is related to the modulation of the harmaline-increased neuronal activity in the tremor network which includes the inferior olive, cerebellar cortex and motor cortex. Potential mechanisms underlying the above pramipexole action are discussed.

• Authors: Barbara Kosmowska, Krystyna Ossowska, Jadwiga Wardas
• Journal: Neurochemical research (Neurochem Res) Vol. 45 Issue 7 Pg. 1518-1525 (Jul 2020) ISSN: 1573-6903 [Electronic] United States
• PMID: 32172399 (Publication Type: Journal Article)

Chemical References

• Antiparkinson Agents
• Central Nervous System Stimulants
• Early Growth Response Protein 1
• Egr1 protein, rat
• RNA, Messenger
• Pramipexole
• Harmaline

Topics

• Animals
• Antiparkinson Agents (pharmacology, therapeutic use)
• Brain (drug effects, metabolism)
• Central Nervous System Stimulants (toxicity)
• Early Growth Response Protein 1 (biosynthesis, genetics)
• Gene Expression
• Harmaline (toxicity)
• Male
• Pramipexole (pharmacology, therapeutic use)
• RNA, Messenger (biosynthesis, genetics)
• Rats
• Rats, Wistar
• Tremor (chemically induced, drug therapy, metabolism)