• Journal of Microbiology and Biotechnology
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• v.21 no.7
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• pp.757-765
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• 2011

Many studies have suggested that the behavioral and reinforcing effects of morphine are induced by hyperactivation of the mesolimbic dopaminergic system, which results in increases in locomotor activity, c-Fos expression in the nucleus accumbens (NAc), and tyrosine hydroxylase (TH) in the ventral tegmental area (VTA). In order to investigate the effect of wild ginseng (WG) on treating morphine addiction, we examined the behavioral sensitization of locomotor activity and c-Fos and TH expression in the rat brain using immunohistochemistry. Intraperitioneal injection of WG (100 and 200 mg/kg), 30 min before administration of a daily injection of morphine (40 mg/kg, s.c.), significantly inhibited morphine-induced increases in c-Fos expression in NAc and TH expression in VTA as well as in locomotor activity, as compared with Panax ginseng. It was demonstrated that the inhibitory effect of WG on the behavioral sensitization after repeated exposure to morphine was closely associated with the reduction of dopamine biosynthesis and postsynaptic neuronal activity. It suggests that WG extract may be effective for inhibiting the behavioral effects of morphine by possibly modulating the central dopaminergic system and that WG might be a useful resource to develop an agent for preventing and treating morphine addiction.

• Journal of Ginseng Research
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• v.46 no.1
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• pp.147-155
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• 2022

Background: Methamphetamine (METH) is the most widely used psychostimulant and has been known to exhibit reinforcing effects even after long abstinence. We showed the inhibitory effect of Korean Red Ginseng extract (RGE) on METH-induced addictive behaviors in animal models mimicking the human drug-use pattern. Methods: We first investigated the effect of RGE on the acquisition of METH-induced dependence using self-administration and conditioned place preference (CPP) tests. Additionally, further experiments such as METH-induced motivational behavior and seeking behavior were conducted. To study the underlying mechanism, dopamine receptor, dopamine transporter, and N-methyl-D-aspartate receptor were assessed through Western blot analysis. Results: Treatment with RGE significantly reduced METH-induced self-administration on a fixed-ratio 1 schedule of reinforcement. It could be also decreased a progressive ratio schedule, and inhibited METH-primed reinstatement. In CPP, RGE significantly prevented the development of METH-induced CPP. Moreover, RGE not only shortened the withdrawal period clearly, but also prevented the reinstatement of CPP. RGE treatment also reversed METH-induced overexpression of dopamine transporter, dopamine receptor D1, and NMDA receptor in the nucleus accumbens. Conclusion: Our findings reflect that RGE has therapeutic potential to suppress METH-induced addictive behaviors by regulating dopaminergic and NMDAergic system.

• International Journal of Oral Biology
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• v.34 no.3
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• pp.123-129
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• 2009

Taste is associated with hedonic evaluation as well as recognition of quality and intensity. Taste information is sent to the cortical gustatory area in a chemotopical manner to be processed for discrimination of taste quality. It is also conveyed to the reward system and feeding center via the prefrontal cortices. The amygdala, which receives taste inputs, also influences reward and feeding. In terms of neuroactive substances, palatability is closely related to benzodiazepine derivatives and $\beta$-endorphin, both of which facilitate consumption of food and fluid. The reward system contains the ventral tegmental area, nucleus accumbens and ventral pallidum and finally sends information to the lateral hypothalamic area, the feeding center. The dopaminergic system originating from the ventral tegmental area mediates the motivation to consume palatable food. The actual ingestive behavior is promoted by the orexigenic neuropeptides from the hypothalamus. Even palatable food can become aversive and avoided as a consequence of postingestional unpleasant experience such as malaise. The brain mechanism of these aspects of taste is elucidated.

• The Korean Journal of Pharmacology
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• v.21 no.2
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• pp.99-110
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• 1985

Majarine that was isolated from Berberis Koreasra Palibin (Berberidaceae) is the isoquinoline alkaloid. The effects of dopaminergic and serotonergic antagonists on majarine induced changes in body temperature were studied in the mouse. Intraperitoneal administration of majarine produced dose-dependent hypothermia. At a dose of 0.1 mg/kg, majarine caused a slight increase in body temperature. Majarine-induced hyperthermia was attenuated by the 5-HT antagonist, cyproheptadine However, it caused hyothermia in mice pretreated with the DA antagonist, haloperidol, and hyperthermia in mice pretreated with haloperidol and cyproheptadine in comparision with haloperidol pretreatment. At a dose of 2.0 mg/kg, majarine-induced hypothermia was attenuated by haloperidol and cyproheptadine, respectively. In reserpine pretreated mice, majarine produced dose-dependent hypothermia. At a dose of 0.1 mg/kg, majarine pretreated with haloperidol caused no significant effect in body temperature. At a dose of 2.0 mg/kg, majarine-induced hypothermia was attenuated by haloperidol pretreatment in mice treated with reserpine and ${\alpha}$-methyl-p-tyrosine. These data suppose that both dopaminergic and serotonergic mechanisms in the brain mediate the effects of majarine on body temperature. We propose that majarine directly stimulate DA receptor, which secondarilly activate 5-HT neurons to cause changes in body temperature.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.1-18
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• 2012

Schizophrenia is a devastating psychiatric illness that afflicts 1% of the population worldwide, resulting in substantial impact to patients, their families, and health care delivery systems. For many years, schizophrenia has been felt to be associated with dysregulated dopaminergic neurotransmission as a key feature of the pathophysiology of the illness. Although numerous studies point to dopaminergic abnormalities in schizophrenia, dopamine dysfunction cannot completely account for all of the symptoms seen in schizophrenia, and dopamine-based treatments are often inadequate and can be associated with serious side effects. More recently, converging lines of evidence have suggested that there are abnormalities of glutamate transmission in schizophrenia. Glutamatergic neurotransmission involves numerous molecules that facilitate glutamate release, receptor activation, glutamate reuptake, and other synaptic activities. Evidence for glutamatergic abnormalities in schizophrenia primarily has implicated the NMDA and AMPA subtypes of the glutamate receptor. The expression of these receptors and other molecules associated with glutamate neurotransmission has been systematically studied in the brain in schizophrenia. These studies have generally revealed region- and molecule-specifi c changes in glutamate receptor transcript and protein expression in this illness. Given that glutamatergic neurotransmission has been implicated in the pathophysiology of schizophrenia, recent drug development efforts have targeted the glutamate system. Much effort to date has focused on modulation of the NMDA receptor, although more recently other glutamate receptors and transporters have been the targets of drug development. These efforts have been promising thus far, and ongoing efforts to develop additional drugs that modulate glutamatergic neurotransmission are underway that may hold the potential for novel classes of more effective treatments for this serious psychiatric illness.

• Biomolecules & Therapeutics
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• v.6 no.1
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• pp.25-30
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• 1998

The roles of dopamine(DA) and N-methyl-D-aspartate(NMDA) system in the development and expression of morphine dependence were investigated by monitoring the concentrations of extracellular DA and its metabolites by in vivo microdialysis and simultaneous observation of behavioral changes in morphine dependent rats. Extracellular DA level in caudate putamen of morphine-dependent rat was decreased and the concentrations of its metabolites, dihydroxy phenylacetic acid(DOPAC) and homovanillic acid(HVA), were increased during naloxone-precipitated withdrawal. DA contents were recovered to normal levels by pretreatment of MK-801, a noncompetitive NMDA receptor antagonist, which may explain the mechanism of diminishing effect of MK-801 on withdrawal symptoms in morphine-dependent rats. MK-801(0.3 mg/tg, i.p.) induced the untoward hamful neurological signs such as ataxia and severe rotations, which may be produced by hyperactivation of dopaminergic system. These results suggest that MK-801 may inhibit the expression of mophine dependence by altering the dopamine release.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.2
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• pp.152-157
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• 2007

Imaging of the dopamine transporter (DAT) provides a marker for the integrity of presynaptic nigrostriatal dopaminergic system. DAT density is reduced in Parkinson disease, multiple system atrophy, and progressive supranuclear palsy. In patients with suspicious parkinsonism, normal DAT imaging suggests an alternative diagnosis such as essential tremor, vascular parkinsonism, or drug-induced parkinsonism. DAT imaging is a useful tool to aid clinician's differential diagnosis in parkinsonism.

• Korean Journal of Oriental Medicine
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• v.15 no.3
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• pp.53-61
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• 2009

Oxytocin(OT), classically known to stimulate labour and milk ejection, contributes to play an important role in a wide range of behavioral effects including drug addiction. An increasing body of evidence suggests that OT ameliorates acute and long-term effects of commonly used drugs by means of interacting with the mesolimbic dopamine system. Mesolimbic dopamine system is thought to play a major role in the reinforcing properties of drug abuse. Oxytocin receptors in the nucleus accumbens(NAc) and ventral tegmental area(VTA) have been implicated in the regulation of reinforcing effects in abused drugs. In the same way acupuncture may attenuate the reinforcing effects of abused drugs in the NAc and VTA. We have an interest in similar liaison between the substrates of acupuncture and drug addiction that may involve OT. Here, we described the possibility that acupuncture modulates the reinforcing and sensitizing properties of abused drugs in the dopaminergic system via the regulation of activities in the oxytocinergic system. The elements in this paper are summarized as follows : neuroanatomical studies of oxytocinergic innervation and distribution of oxytocin receptors; experiments related to the methamphetamine, cocaine, morphine and ethanol; experiments related to the oxytocin and acupuncture.

• The Journal of Korean Medicine
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• v.26 no.3 s.63
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• pp.1-12
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• 2005

Objectives : Substantial evidence suggests that reinforcing effects of nicotine can be mediated by the mesolimbic dopaminergic system. It has been shown that repeated injections of nicotine produce an increase in locomotor activity and expression of the immediate-early gene, c-fos, in the dopaminergic target areas. Herbal medicine as a therapeutic intervention has been widely used for the treatment of mental dysfunction. Many studies have shown that Radix Scutellariae (RS) can affect the biochemical balance in the central nervous system. Tn order to investigate whether RS has an influence on nicotine-induced behavioral sensitization, we examined the effect of RS on nicotine-induced locomotor activity and c-fos expression in the striatum and nucleus accumbens utilizing the fos-tike immunohistochemistry (FLI). Methods : Male SD rats received RS (200mg/kg, i.p.) 30min before repeated daily injections of nicotine (0.4mg/kg, s.c.) for 7 days. This was followed by withdrawal for 3 days and one challenge for 1 day. Results : System challenge with nicotine produced a much larger increase in locomotor activity and accumbal FLI. Pretreatment with RS significantly inhibited nicotine-induced locomotor activity and FLI in the striatum and nucleus accumbens. Conclusions : These results demonstrate that reduction in locomotor activity by RS may be reflected by reduction of dopamine release and postsynaptic neuronal activity in the striatum and nucleus accumbens. Our results suggest that RS may have therapeutic effect on nicotine addiction.

• Sleep Medicine and Psychophysiology
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• v.17 no.1
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• pp.5-10
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• 2010

Restless legs syndrome (RLS) is a common sensorimotor disorder that is characterized by an urge to move the legs and peculiar, unpleasant sensations deep in the legs and its prevalence in the general population is between 3.2% and 15%. RLS significantly impairs patients' lives, often by severely disrupting sleep. However, both clinicians and patients under-recognize the RLS. RLS phenotypes include an idiopathic form and secondary form that is usually resulted from various causative conditions. The pathophysiology of RLS may be related with the dopaminergic system, which is closely linked to a number of psychotropic medications, including antidepressant and antipsychotics. Several antidepressants and antipsychotics have been shown to induce or exacerbate RLS. We need pay attention to the fact that commonly prescribed medications can be the cause of RLS.