INTRODUCTION
Hyperexcitability of the central nervous system (CNS) has been a major problem that underlies most of ethanol
withdrawal symptoms. It has been regularly found when ethanol consumption is reduced or completely stops
(Hendricson et al., 2007; Bailey et al., 1998). Consequently, many behaviors emerge as result of cortical excitation.
Overactivation of NMDA-type glutamate receptors (Haugba et al., 2005) and suppression of GABA
A
receptor activity
(Mhatre et al., 1993) were found during early phase of ethanol withdrawal. Central monoaminergic systems also play
important roles in the development of some ethanol withdrawal symptoms. Serotonergic dysfunction has been observed
during ethanol withdrawal period (Heinz et al., 1998; Kelai et al., 2003). Some of previous studies found that serotonin
levels were decreased in various brain regions of rat brain during chronic ethanol consumption and ethanol withdrawal
(Uzbay etal., 1998; Mirovsky et al., 1995). There might be a correlation between decreased serotonergic activity and
ethanol withdrawal symptom. Thus, enhancement of serotonergic function by selective serotonin reuptake inhibitors
(SSRIs) could be effective in treatment of ethanol withdrawal.
Many drugs have been applied to prevent against the ethanol withdrawal syndrome. Most common drugs
popularly used to treat ethanol withdrawal syndrome are anxiolytic (Verleye et al., 2009) and antidepressant groups.
However, the use of anxiolytics such as benzodiazepines has been found to develop dependence and sedative actions by
themselves (Pratt et al., 1998; Landry et al., 1992).
Mitragyna speciosa
Korth. (MS) is a native tropical plant mainly found in Southeast Asian countries
particularly in Thailand and Malaysia. This plant belongs to the family Rubiaeceae. It is traditionally used to treat
diarrhea, fever, asthma and coughing. In addition, it was also used to substitute for opium or morphine in the treatment
program. Farmers and laborers often chew fresh leave or smoke the dry leaves of MS to increase work efficiency and
tolerance of hard work (Jansen and Prast, 1988). Over 22 indole alkaloids from the MS
have been isolated including
mitragynine a main constituent (~66.2% based on the crude extract) (Takayama, 2004). Most studies have focused on
pure mitragynine and its antinociceptive action on the brain trough μ- and
δ
-opioid receptor (Matsumoto et al., 1996;
Thongpradichote et al., 1998). In addition, it was found that noradrenergic and serotonergic systems were involved in the
antinociceptive effect of mitragynine. Moreover, 7-hydroxymitragynine, a minor constituent, possess antinociceptive
effects with high affinity for opioid receptors and its potency was 30- and 17-fold higher than those of mitragynine and
morphine, respectively (Horie et al., 2005; Matsumoto et al., 2004).
Previously, antidepressive activity of the MS extracts was demonstrated by using behavioral studies. Its action
may be partially mediated through stimulations of serotonergic (Kumarnsit et al., 2007) and HPA axis pathways (Farah
ET AL., 2010). These findings have brought the idea of MS application for ethanol withdrawal treatment. Until recently,
a pilot study in our laboratory has already shown that aqueous extract from the MS attenuated some ethanol withdrawal
induced-specific behaviors (Kumarnsit et al., 2007b).
This study utilized EEG recording technique that would allow quantifying the severity levels of ethanol
withdrawal and the effectiveness of treatment. Sleep disturbance has been found during ethanol withdrawal Ehlers and
Slawecki, 2000). EEG signals were also used for analysis of wakefulness period to evaluate severity of ethanol
withdrawal and treatment.
