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BBRC Vol 14 No 04 2021-18
BBRC Vol 14 No 04 2021-18
Pharmacological Communication
ABSTRACT
Although the implication of calcium signalling in the aetiology of anxiety remains elusive, drugs modulating calcium (like calcium
channel blockers) have been discovered to be somewhat beneficial as treatment option for anxiety related disorders. This study was
therefore undertaken to assess probable ameliorative potential of verapamil against manic-like (stereotype behaviour) and anxiety-
like symptoms in mice exposed to sleep deprivation. Mice were allotted into five treatment groups (n=5): group 1 and 2 received
10 mL/kg distilled water, groups 3 and 4 verapamil (25 and 50 mg/kg) while group 5 received astaxanthin (50 mg/kg) which served
as the reference drug. Treatment was for 7 days and animals were sleep-deprived on the final 72 hours. Various behavioural tests to
determine degree of stereotypical behaviour and locomotor activity were carried out. Anxiety test was done via the aid of a light/dark
box and plus maze while stereotype behaviour was assess utilizing an open field box. Oxidative stress parameters; malondialdehyde
and glutathione were assessed. Histopathological perturbations in the caudate putamen were also recorded. Data were subjected to
ANOVA at α0.05. The results obtained suggest that verapamil significantly suppressed stereotyped behaviour and reduced the incidence
of manic-like behaviour which was induced by paradoxical sleep deprivation. Verapamil also significantly restored antioxidant levels
and protected against loss of caudate neurons. In conclusion, verapamil ameliorates manic-like symptoms and anxiety in mice deprived
of sleep, while protecting brain neurons against oxidative stress damage induced by sleep deprivation.
1487 Verapamil improved mania-like symptoms in sleep-deprived mice BIOSCIENCE BIOTECHNOLOGY RESEARCH COMMUNICATIONS
Eduviere et al.,
which treatment with lithium attenuated (Benedetti et al. However, the results obtained revealed that verapamil, at
2008; Armani et al. 2012; De Miranda et al. 2020). As both doses, caused a significant reversal in hyperactivity
obtainable in Table 1 and Figure 1 below, sleep deprivation and the various stereotype behaviours. Thus, indicating the
significantly increased manic-like behaviour in PSD mice. probable use of verapamil in the reduction or attenuation
of manic like symptoms.
Figure 1: Effect of verapamil on motor coordination in mice Table 2. Effect of verapamil on anxiety in sleep deprived
subjected to paradoxical sleep deprivation. mice using the light/dark box
The tests for anxiety were conducted using a light/dark group, and for the plus maze, the mice spent significant time
box and plus maze. Sleep deprived animals spent longer in open arm than closed arm, thus signifying that verapamil
period in the dark box compared to animals that were not could possibly be used to attenuate the symptoms of anxiety
sleep deprived. In the plus maze, the sleep deprived mice associated with sleep deprivation (Table 2 and Table 3).
expended much time in the closed arm than open arm;
signifying classic indication of anxiety. However significant Each bar represents mean ± S.E.M of grouped mice (n=6).
variations were observed when verapamil was administered # specifies significant (p < 0.05) difference compared
– the mice spent lesser period in the dark box and more in to vehicle. * specifies significant (p < 0.05) difference
the light box compared to the vehicle plus sleep deprived compared to the vehicle + SD. (One-way ANOVA and
BIOSCIENCE BIOTECHNOLOGY RESEARCH COMMUNICATIONS Verapamil improved mania-like symptoms in sleep-deprived mice 1488
Eduviere et al.,
post-hoc test; Student-Newman-Keuls). VEH: Vehicle, et al. 2020). Furthermore, PSD alters membrane fluidity,
AXT: Astaxanthin, VPL: Verapamil, SD: Sleep deprivation. calcium ion (Ca2+), concentration, gene expression, and
under/beneath All the Tables and figures, except for figure enhances metabolic rate (Ramanathan et al. 2002; Singh et
6. al. 2008; Mathangi et al. 2012; Ben-Azu et al. 2020).
Verapamil on brain oxidative stress in sleep-deprived Verapamil on pain and nociception in sleep-deprived
mice: Results obtained indicate that verapamil produced an
Figure 2: Effect of verapamil on brain malondialdehyde
anti-nociceptive effect by reducing the pain threshold and
levels in mice subjected to sleep deprivation
increasing reaction time of PSD mice as recorded by the two
tests; hot plate (Figure 4) and tail flick (Figure 5). This gives
an indication that verapamil may be useful in the mitigation
of pain in patients who experience sleep difficulties. This
also supports previous studies which showed that PSD
contributes to hyperalgesia. It is, thus, logical to infer that
PSD aggravates chronic pain symptoms in patients (Smith
et al. 2000). Also, patients with pain disorders normally
suffer anxiety due to the strain associated with living with
pain. Note that the effect of verapamil on pain differs
depending on dose, route of administration and pain test
utilised (Tamaddonfard et al. 2014).
1489 Verapamil improved mania-like symptoms in sleep-deprived mice BIOSCIENCE BIOTECHNOLOGY RESEARCH COMMUNICATIONS
Eduviere et al.,
the principal brain mechanism at the core of the impact of of neuronal damage and also an increase of viable neuronal
sleep deficits on nociception remains unknown (Stroemel- cells in PSD mice.
Scheder et al. 2020).
Counts were based on neuronal nuclei present in three
(3) squares per slide, using the pre-calibrated Image J
software.
Figure 6: Photomicrograph of the caudate putamen of mice
after paradoxical sleep deprivation
Conclusion
The finding of the present experiment suggests that
verapamil attenuated anxiety/manic-like behaviour induced
via deprivation of REM phase sleep, through a mechanism
believed to be associated with reduced oxidative stress, and
neuronal damage. Verapamil also significantly restored
antioxidant levels and protected against loss of caudate
neurons. In conclusion, verapamil ameliorates manic-like
symptoms and anxiety in mice derived of sleep, while
protecting brain neurons against oxidative stress damage
induced by sleep deprivation.
Acknowledgements
This work was technically supported by the laboratory
technicians of Pharmacology laboratory, DELSU.
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