Yonago Acta medica 2005;48:83–92

Effects of Metoclopramide Hydrochloride, a D2-Selective
Dopamine Receptor Antagonist, on the Fast Oscillation ofthe Electrooculogram
Norio Miki*, Hiroshi Nakao†, Jiro Hasegawa, Takashi Baba, Ryoko Ishikura, Akiko
Kakimaru, Keiko Sakatani, Atsushi Yamasaki, Yuji Sasaki and Akihiko Tamai‡
Division of Ophthalmology and Visual Science, Department of Medicine of Sensory and MotorOrgans, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, *Clinicof Ophthalmology, Miki Eye Clinic, Tottori 680-0801, †Clinic of Ophthalmology, Nakao EyeClinic, Nishiwaki 677-0021 and ‡Clinic of Ophthalmology, Hino Hospital Association Hino Hospital, Hino 689-4504 Japan

Fast oscillation (FO) of an electrooculogram (EOG) was recorded in both eyes of 10
healthy volunteers before and after administration of metoclopramide hydrochloride(MTCL), a D2-selective dopamine receptor antagonist, paying particular attention to sex
concerning sensitivity to dopamine in young subjects. Healthy volunteers were divided
into male and female groups; 5 males (10 eyes) aged 21 to 23 years (average, 21.8 years)
and 5 females (10 eyes) aged 19 to 25 years (average, 21.8 years). As an FO parameter,
the df FO (the averaged difference in µV between maximum amplitude in the dark period
and minimum amplitude in the light period during FO measurement) was evaluated.
The mean level of df FO signiﬁcantly increased between phase A (the initial 10 min before
intravenous injection of 10 mg of MTCL) and phase B (10 min after the injection) in themale and female groups (P < 0.01 and P < 0.025) and between phase A and phase C (theadditional 10 min after the injection) in both groups (P < 0.01 and P < 0.05). The meanlevel of df FO in the female group was signiﬁcantly higher than that of the male group inphase B (P < 0.05). As a control, the experimental procedure was performed with physiological saline administration, and no changes were observed. The data suggest that
there exists some difference between young males and females generation concerning
sensitivity to dopamine and that young females may show a higher-than-male sensitivity
to dopamine in the occurrence of FO potential.
Key words: D2-selective dopamine receptor antagonist; dopamine; electrooculogram; fast oscillation; metoclopramide hydrochloride

Fast oscillation (FO) of the electrooculogram(EOG) is the rapid initial deflection of opposite
polarities occurring at the initial stage of the lightand dark periods in the EOG procedure (Kolderand Brecher, 1966; Kolder, 1974). That is, FOshows a peak in the dark adaptation (dark peak)
and a trough in the light adaptation (light trough)in response to dark and light periods of approximately 1.1 min each. FO is distinct from ordinary
slow oscillation (SO) of the EOG which shows aAbbreviations: df FO, averaged difference in µV between maximum amplitude in the dark period and minimum amplitude in the light period during FO measurement; EOG, electrooculogram; FO, fast oscillation; MTCL, metoclopramidehydrochloride; SO, slow oscillation

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tential. In this report, we have tested the effectsof MTCL on FO in 10 healthy volunteers aged
19 to 25 years, paying particular attention to theexistence of difference in sex concerning sensitivity to dopamine in young subjects, since Nakao
and others (1994) postulated the possibility intheir experiment, in which ﬂuctuations in the FO
potential obtained from female normal subjects
averaging 22.7 years of age were relatively larger
than those from normal male subjects averaging
24.3 years of age.

trough in the dark adaptation (dark trough) anda peak in the light adaptation (light peak) in response to dark and light periods of approximately
12.5 min each (Kolder and Brecher, 1966; Kolder,1974; Welber, 1989).
Concerning the origin and occurrence of FOand SO, Steinberg and others (1983) reported theinvolvement of the retinal pigment epithelium,
mainly its basal membrane in the FO potential,
while Arden and others (1962) reported the involvement of the retinal pigment epithelium andphotoreceptor complex in the SO potential.
Joseph and Miller (1991) suggested that thedownward oscillation of FO might result froma delayed hyperpolarization associated with increased electric resistance of the basal membraneof the retinal pigment epithelium. The delayed
hyperpolarization is thought to be caused by adecrease in intracellular chloride, which is linked
to the light-induced drop in subretinal potassium
concentration (Joseph and Miller, 1991). The upward oscillation of FO is thought to result froma depolarized change associated with decreased
electric resistance of the basal membrane of theretinal pigment epithelium. This depolarized condition of the basal membrane may be caused byan increase in intracellular chloride of the retinal
pigment epithelium, which is linked to the darkinduced recovery in subretinal potassium concentration (Nikara et al., 1974).
On the other hand, dopamine, a retinal neurotransmitter, has been known to be indispensablefor the process of generation and delivery of electric excitement in the ordinary SO potential (Dawisand Niemyer, 1986; Jaffe et al., 1987; Gallemoreet al., 1988; Maruiwa et al., 1992). According
to the results of an experiment in a report byMaruiwa and others (1992), metoclopramide hydrochloride (MTCL), a D2-selective dopamine receptor antagonist (Schulze-Delrieu, 1979), which
was given intravenously in 5 healthy volunteers
aged 23 to 33 years, increased the dark-adapted
SO amplitudes transiently and suppressed thelight-adapted SO amplitudes.
However, little has been known of the reaction and influence of dopamine on the FO po-

Subjects and Methods
Subjects
In this study, 10 healthy volunteers aged 19 to 25years with normal, functional eyes (20 eyes), in
whom error of refraction did not exceed ± 3 diopters, were tested at the Department of Ophthalmology, Tottori University Hospital. The healthy
volunteers were divided into male and female
groups; 5 males (10 eyes) aged 21 to 23 years (average, 21.8 years) and 5 females (10 eyes) aged 19to 25 years (average, 21.8 years).
Before the trial, the purpose of the experiment and the tasks to be performed were fully explained to each volunteer, and written consent wasobtained. All procedures conformed to the tenetsof the Helsinki Declaration.
Apparatus and methods for FO recording
Using a newly devised automated electrooculograph, a Nidek EOG-2 (Nidek, Gamagori, Japan)(Nakao et al., 1994; Inoue et al., 2003; Tamai
et al., 2004), FO was recorded in each subject.
The EOG-2 consists of a dome, a personal computer, an index controller, an ampliﬁer, a printerand an EOG pen recorder. Inside the dome isa hemispheric screen with a radius of 300 mm.
Four tungsten lamps (115 V, 50 W each) produce a background luminance of 1,270 lux whenmeasured at the location of the subject’s eyes. In
this study, the background light was periodically84

Effects of MTCL on EOG fast oscillation

Fig. 1. Calculation method for df FO as an
FO parameter in this survey. AD, maximum
amplitude in the dark period; AL, minimum
amplitude in the light period during FO measurement. n, number of pairs (alternatingdark-light period of 1 min each), 5 pairs intotal. df FO was calculated only if at least 3
successive pairs were observed (5 ≥ n ≥ 3).

were 10 measurements in each period. Six out of
10 EOG amplitudes were automatically averaged
and recorded at the end of each period throughthe EOG artifact rejection system on the Nidek
EOG-2 (Inoue et al., 2003; Tamai et al., 2004).
In this study, the calibration sensitivity for the pen
recorder was 200 µV/division on the printer. The
time constant of the ampliﬁer was set at 3 s, and ahigh frequency cutoff of –3 dB was set at 20 Hz.

turned on and off at intervals of 1 min with theaid of the computer.
For every subject, cup-shaped silver-silver
chloride conductive electrodes, 8 mm in diameter,
were placed beside both canthi of each eye on theorbital margin, and a grounding electrode withthe same cup shape was placed on the left earlobe,
as routinely used. Before setting these electrodes,
the skin was cleaned with 90% alcohol, and thenthe electrodes were applied with a conductive
paste. Electrode resistance was below 10 kΩ. Under these conditions, simultaneous recording of
the FO potentials from each eye of every subject
was possible.
Mydriasis can provide better control of retinal illumination. However, FO recording wasperformed without mydriasis, because mydriasis
may increase discomfort in subjects. Before theFO recording, a 10-min pre-light adaptation period at a background luminance level of 1,270 lux
was given. Then the subjects were introduced toﬁxate alternately on a pair of targets on the screen
inside the dome. The two targets subtended 40˚ tothe visual angle were presented alternately with afrequency of 0.5 Hz.
After this adaptation period, the dome wasperiodically illuminated for 1 min followed by 1
min of darkness for 30 min. The FO potentials
showed peaks in darkness and troughs in lightnear the end of the dark and light periods respectively; that is, between 45 s and 55 s after the startof each period (De Rouck and Kayembe, 1981).
Therefore, the FO measurements were performed
at 40 to 60 s in each dark and light period; there

Administered agent and control solution
After the initial 10 min of alternating dark andlight periods (phase A), 10 mg of MTCL in 2 mLof Primperan injection (Fujisawa PharmaceuticalCo. Ltd., Osaka, Japan) was given intravenously
from the median cubital vein of each subject inless than 10 s. FO was further recorded for another 20 min (phases B and C, 10 min each, respectively). For the nonchemical control, each subject
was asked to receive another set of examinations
with an intravenous injection of 2 mL of physiological saline. The control examination wasscheduled after an interval of at least 2 weeks.
FO parameter
As an FO parameter, df FO, which is the averaged
difference in µV between maximum amplitude in
the dark period and minimum amplitude in thelight period during FO measurement (De Rouckand Kayembe, 1981; Nakao et al., 2003; Tamai etal., 2004) (Fig. 1), was evaluated. In the present
study, each phase showed 5 dark-rise and light-fall85

N. Miki et al.

MTCL (10 mg)administered researchControl solutionadministered research

AB

CABCA

BCAB

CA

BCABC

Subject 1(22 years)

Subject 4(22 years)

Subject 5(21 years)

Fig. 2. Some samples of FO patterns of 5 male test subjects. The dotted line in each sample shows FO pattern in theright eye and the solid line shows that in the left eye. Control solution: physiological saline. A, phase A: initial 10 min
before intravenous injection; B, phase B: following 10 min after the injection; C, phase C: additional 10 min after theinjection. A dark arrow in each sample indicates the injection point. , dark period; , light period (horizontal axis).

zigzag FO patterns (5 pairs of FO measurements),
according to the alternating dark-light period of1 min each. df FO was calculated only if at least 3
successive pairs were observed (Fig. 1). Isolated
and occasional FO patterns were not taken into
account.

Statistical analysis
All values were expressed as mean ± SD. Statistical analysis was performed with Wilcoxon’s
rank sum test of correspondence or non-correspondence. Values of P < 0.05 were consideredsigniﬁcant.
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