CNS dopamine agonistic action of the Vitex agnus-castus extract Ze 440 in freely moving, chronically instrumented animals

Background

Dopamine agonistic action is intensively under investigation because of its usefulness in movement disorder. Extracts prepared from Vitex agnus-castus (VAC) showed remarkable dopamine agonistic actions believed to inhibit exaggerated prolactin release in premenstrual syndrome.

Method

In order to investigate whether oral administered VAC besides inhibition of stimulated prolactin release might induce general dopamine action within the central nervous system (CNS), the pattern of field potentials was recorded from electrodes positioning at frontal cortex, hippocampus, striatum and reticular formation. All four electrodes were placed 3mm lateral within the left hemisphere (anterior coordinates are 12.2, 5.7, 9.7 and 3.7, according to the atlas of Paxinos and Watson). Animals were given 2 weeks for recovery from the surgical procedure. The electrical activity was amplified and wireless transmitted from the freely moving rats. Signals were collected in sweeps of 4s duration and submitted to Fast Fourier transformation. The resulting power spectra were divided into 6 frequency ranges (delta, theta, alpha1, alpha2, beta1 and beta2). Spectra were averaged in steps of 3 minutes each and displayed online. In an off-line procedure spectra were averaged to provide 60 minutes periods for data presentation and further statistical analysis. Changes of electrical power (µV2/ω) are expressed as % of the 45min absolute pre-dose electrical power values within each frequency band. Motion was measured by a video tracking system (GJB Datentechnik, D-98704 Langewiesen).

Results

Oral administration of saline did not show any changes in the EEG power spectrum. Administration of 10, 25 and 50mg of the special VAC extract Ze 440/kg BW changed dose related the alpha 2 frequency band as well as delta and theta frequencies predominantly in frontal cortex and striatum. Changes in dopaminergic transmission could be attributed to modulation of alpha2 frequencies in the past and can therefore be regarded as a validated biomarker. The largest effect was caused by 25mg Ze 440/kg BW. Administration of a potent dopamine D2 receptor blocker (L 741,626; 2mg/kg BW) prior to oral administration of 25mg Ze 440/kg BW abolished the EEG responses in the frontal cortex but not those in the striatum. Oral administration of 10, 25 or 50mg Ze 440/kg BW prevented the normal decrease of movements with time, whilst the combination of 25mg Ze 440/kg BW with the dopamine D2 antagonist increased the movement.