EN
Harmaline, a derivative of beta-carboline is a well-known tremorgenic compound which induces the action and postural tremor in animals. Oscillation frequency of this symptom is equal to 10–12 Hz in rats. A synchronous activation of the olivo-cerebellar pathway and release of glutamate in the cerebellum has been suggested to be a primary cause of the harmaline-induced tremor. Subtype 4 of metabotropic glutamate receptors (mGluR4) is mainly an autoreceptor and its stimulation decreases glutamate release. MGluR4 receptors are abundant in the cerebellum and therefore their influence on the harmaline-induced tremor might be expected. However, mechanisms underlying this symptom are more complex and seem to involve also other neurotransmitter systems, especially the noradrenergic neurotransmission in the cerebellum. The aim of the present study was to examine an influence of an orthosteric agonist of mGluR4 – AF22898:8 on the tremor induced by harmaline in rats. An antagonist of beta-adrenoceptors – propranolol was used as a reference compound. Tremor of animals was measured automatically by actimeters where four force tranducers measured the force exerted by an animal on the floor. The Power Spectra analysis which uses a Fourier transform generated power spectra for examination of the tremor. The average power over three specific frequency bands AP1 (0–8 Hz), AP2 (9–15 Hz), AP3 (16–25 Hz), and tremor indices, which quantified the differences in power between the AP2 and AP1 (T1) and AP3 and AP1 (T2) were used to quantify the tremor intensity. Harmaline in doses of 7.5–25 mg/kg i.p. induced the generalized tremor which was dose-dependent and lasted longer than 2 h. Propranolol in a dose of 20 mg/kg i.p. diminished the tremor (decreased T1 and AP2) induced by harmaline (15 mg/ kg i.p.). In contrast, AF22898:8 administered in doses of 2.5–20 mg/kg i.p. was ineffective. The present results indicate that the harmaline-induced tremor measured in the force plate actimeters consititute a good model for screening antitremorgenic compounds. However, in contrast to earlier expectations the agonist of mGluR4 had no influence on this symptom.The study was supported by the grant of the National Science Centre nr N N401 570638, and partly by Statutory Funds of the Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland.