• 수면정신생리
• /
• 제10권1호
• /
• pp.26-31
• /
• 2003

Restless leg syndrome (RLS) and periodic limb movement of sleep (PLMS), often concurrent, come under diagnosed disorders of sleep and treatable condition. RLS symptoms are evoked in the limbs at rest and increase in the evening and during the night. PLMS is characterized by periodic episodes of repetitive limb movements caused by muscle contractions during sleep. RLS is often associated with a sleep complaint and PLMS. Both RLS and PLMS represent one of the most commonly encountered sleep disorders in a primary care setting. The circadian rhythm and the presence of PLMS cause sleep disturbances in RLS. The emphasis on pathophysiology includes consideration of central nervous system localization, neurotransmitter, and the role of iron metabolism. Dopaminergic agents are considered the treatment of choice for RLS and PLMS. With proper diagnosis and effective treatment patients' ability to fall asleep and maintain sleep improves, and their sense of well being increases.

• 생물정신의학
• /
• 제18권2호
• /
• pp.61-71
• /
• 2011

Substance addiction is a chronically relapsing disorder that has been characterized by a vicious cycle composed of intoxication, craving/anticipation, withdrawal, and response inhibition/bingeing. Here we summarize the findings from neuroimaging studies in addiction according to these behavioral components and suggest the integrated neurobiological model of drug addiction and related brain correlates. The roles of various prefrontal regions, thalamus, memory circuit, anterior cingulated, and insula were also suggested in addition to those of classical mesolimbic dopaminergic system and its responsivity. Limited studies of behavioral addiction demonstrated a similarity with substance addiction on the neurobiological basis. Based on the current understanding of neurobiology of addiction, further researches on interactions of behavioral components and their brain correlates, behavioral addiction, and therapeutic applications will be desired.

• 수면정신생리
• /
• 제15권1호
• /
• pp.17-24
• /
• 2008

Periodic leg movements during sleep (PLMS) are best described as repetitive stereotypical movements of the lower extremities characterized by dorsiflexion of the ankle, dorsiflexion of the toes and a partial flexion of the knee and sometimes the hip. The prevalence of PLMS is about 5-11% in adults and is predicted much higher than previously surveyed. They are also frequently found in various sleep disorders, several disorders not primarily affecting sleep, and patients taking psychiatric medications. Although they are rarely found in children, they are common findings in children referred to a pediatric sleep laboratory. The pathophysiology is strongly associated with decline of central dopaminergic function and closely related to arousal system during sleep. Benzodiazepines, levodopa, dopamine agonists and opioids are generally recommended for treatment but more controlled studies on the effectiveness are needed.

• 약학회지
• /
• 제43권5호
• /
• pp.682-688
• /
• 1999

Abuse liability of ephedrine was investigated by measurement of locomotor activity and self-administration in Sprague-Dawley rats. Locomotor activity was determined in rats treated with 3, 10 and 30 mg/kg ephedrine for 14 days. Self-administration by ephedrine (0.23, 1 and 2.3 mg/kg) was examined in food-trained rats. We also examined effect of dopamine receptor antagonist (spiperone, $30{\;}\mu\textrm{g}/kg$) on the ephedrine-induced response of self-administration. Body weight was not statistically difference between control and ephedrine treatment group, but locomotor activity was dose-dependently increased. Self-administration for ephedrine was decreased in the early response (day 1 and 2) but the response was increased by higher dose of ephedrine. Self-administration was decreased by dopamine receptor antagonist (spiperone). These data showed that ephedrine increased locomotor activity and induced response of self-administration, and the effects of ephedrine were partially related to the dopaminergic system, which suggest the ephedrine may have abuse liability.

• 대한핵의학회지
• /
• 제38권1호
• /
• pp.41-51
• /
• 2004

목적 : 본 연구는 약물에 노출되지 않은 뚜렛 장애 아동들에게 치료 목적으로 일정기간 일정한 용량의 risperidone을 투여한 후 치료 전과 후의 틱증상 척도의 변화 정도와 $[^{123}I]IPT$ SPECT로 측정한 기저 신경절 DAT밀도에 변화가 있는 지 여부를 알아보고자 하였다. 대상 및 방법 :만 $6{\sim}12$세 사이의 아동으로 약물 비노출뚜렛 장애 아동 9명과 11명의 정상 대조군을 대상으로 risperidone 치료 전과 후에서 각각 $[^{123}I]IPT$ SPECT로 측정한 기저 신경절 DAT 밀도에 변화를 정량적 계측하고 치료전 약물 비노출군과 정상대조군의 기저 신경절 DAT 밀도에 차이를 통계적 분석하였으며, 약물 비노출군아동의 치료전과 치료후의 기저 신경절 DAT 밀도에 차이를 통계분석하였다. 결과: 9명의 약물 비노출뚜렛 장애 아동군과 정상 대조군 사이의 좌,우측 기저 신경절 DAT특이결합/비특이결합 비율의 비교한 결과 좌,우측 기저 신경절 모두 DAT특이결합/비특이결합 비율이 정상 대조군에 비해서 증가되어 있었다. (좌측: z=1.576, p=0.043, 우측: z=1.787, p=0.025). 9명의 뚜렛 장애 아동에서 risperidone치료 전과 후 상태에서 기저 신경절 DAT 특이결합/비특이 결합 비율 비교한 결과, risperidone 전후 사이에 유의한 차이가 관찰되지 않았다. (우측: t=-0.974, p=0.362 ; 좌측: t=-0.513, p=0.634). 결론: Risperidone 투여가 뚜렛 장애의 증상을 호전시키는 시점에서 기저 신경절 DAT 밀도는 변화시키지 앓을 수 있음을 제시한다.

• KSBB Journal
• /
• 제20권5호
• /
• pp.363-370
• /
• 2005

중추신경계의 신경간세포가 파킨슨병과 뇌졸중과 같은 퇴행성 뇌 질환의 치료뿐만이 아니라 신경세포 발생과정에서의 중요성 때문에 최근에 커다란 관심의 대상이 되고 있다. 중추신경계의 발생과정 동안에, 중뇌의 도파민 신경세포의 형성은 두 가지의 분자생물학적인 기작에 의해서 결정된다. 첫째로, FGF-8, sonic hedgehog 그리고 전사조절인자 인 Nurr1이 도파민 신경세포의 형질을 결정짓는다. 또 다른 기작으로는, 전사조절인자 인 $Lm{\times}lb$와 $Pt{\times}3$가 중요하게 관련되어있다. 특히 Nurr1이 결핍된 생쥐에서, 타이로신수산화효소 (Tyrosine bydroxylase, TH) 면역양성 세포들이 중뇌흑색질에서 발견되지 않으므로 Nurr1이 도파민 신경세포의 발생에 필수적임을 알 수 있다. 본 연구에서는 도파민 신경세포의 형질을 유도하는데 있어서 Nurr1이 매개하는 기작을 연구하기 위해서 레트로 바이러스를 이용하여 Nurr1을 도입한 무한증식 신경간세포를 사용하였다. Nurr1 유전자의 과발현 만으로는 신경간세포에서 도파민 신경세포의 형질을 유도하지는 못하지만, 레티노이드 (retinoid, RA)와 폴스콜린 (forskolin, FK)을 처리하여 TH와 방향성 L-아미노산 탈카르복시화효소 (aromatic L-amino acid decarboxylase, AADC) mRNA의 발현을 유도하였다. 또한, Nurr1 과발현 신경간세포를 사람 별아교세포와 공동배양 하여 TH 발현량을 많이 증가시켰다. 이러한 공동배양실험에서, RA와 FK를 처리하면 TH의 발현수준이 더욱 더 증가함을 발견하였다. 이러한 결과들은 Nurr1 유전자를 도입한 사람 신경간세포가 파킨슨병 환자들에게 세포이식을 통한 유전자 치료의 유용성을 시사하고 있다.

• 대한약침학회지
• /
• 제7권1호
• /
• pp.53-61
• /
• 2004

Substantial evidence suggests that behavioral and reinforcing effects of cocaine can be mediated by the mesolimbic dopaminergic system. It has been shown that repeated injections of cocaine produce increase in locomotor activity, expression of the immediate-early gene, c-fos in the nucleus accumbens (NAc), which was one of the main dopaminergic terminal areas. Herbal-acupuncture as a therapeutic intervention has been widely used for the treatment of many functional disorders such as drug abuse. Coptidis Rhizoma (CR) and its main component, berberine (BER) were selected as herbal medicine of herbal-acupuncture. Both medicines have been known to have the therapeutic effect on the central nervous system. In order to investigate the effects of CR and BER herbalacupuncture at shenmen (HT7) point (CR/H and BER/H) on the cocaine-induced behavioral sensitization, the influence of CR/H and BER/H on repeated cocaine-induced locomotor activity, the change of c-Fos expression in the brain by immunohistochemistry were examined. Male SD rats were given CR/H (0.4mg/kg) and BER/H (0.1mg/kg) 30 min before daily injections of cocaine hydrochloride (15mg/kg. i.p.) 10 days. After 3 days withdrawal, rats received a challenge injection of cocaine (15mg/kg, i.p.). Systemic challenge with cocaine produced much larger increased locomotor activity, accumbal Fos-like immunoreactivity in the NAc. Pretreatment with CR/H and BER/H significantly inhibited cocaine-induced locomotor activity, the change of c-Fos expression in the rats. Our data demonstrated that the inhibitory effects of cocaine-induced behavioral sensitization by CR/H and BER/H were closely associated with the reduction of presynaptic dopamine release in the NAc. These results suggest that CR/H and BER/H can be effectively applied to cocaine addiction.

• 생명과학회지
• /
• 제19권9호
• /
• pp.1232-1238
• /
• 2009

신경전달물질의 분비는 시냅스전 신경말단의 active zone에 있는 다양한 단백질들에 의해 조절된다. 도파민은 정신분열병, 약물중독과 같은 여러 가지 행동, 정신질환의 병태생리와 연관된 필수적인 신경전달물질이다. 저자들은 본 연구에서 신경 전달물질 분비와 관련된 주요 유전자가 결여 된 knockout (KO) 생쥐의 시냅토좀(synaptosome) 도파민 분비를 측정하였다. 시냅토좀 도파민 흡수와 분비는 [$^3H$]-도파민과 관류실험을 이용하여 시행, 측정하였다. 17 KO 생쥐 가운데 3 종류의 생쥐에서 그들의 littermate 대조군과 비교하였을 때 변화된 도파민 분비를 보였다. $Rim1{\alpha}$ KO에서 세포막 탈분극에 의한 [$^3H$]-도파민은 유의하게 감소되었으며, 또한 $Rim1{\alpha}$의 도파민 신경에서의 조건 KO에서는 생리적 완충용액에 의한 기본적인 도파민 분비 및 세포막 탈분극에 의한 도파민 분비 모두가 유의하게 감소되어 있었다. neurexin3의 도파민 신경에서의 조건 KO에서는 세포막 탈분극에 의한 도파민 분비의 증가를 보였다. 이 데이터들은 도파민 분비와 글루타메이트, GABA와 같은 전통적 신경전달물질 분비의 유사성과 차별성을 설명한다. 결론적으로, $Rim1{\alpha}$와 neurexin3는 시냅스전 도파민 분비의 중요한 조절자이며 신경계 질환과 연관될 가능성이 있다.

• 한국환경성돌연변이발암원학회지
• /
• 제21권1호
• /
• pp.30-33
• /
• 2001

Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, SAL), a dopaminergic isoquinoline neurotoxin, has been implicated to contribute the etiology of Parkinson's disease and neuropathology of chronic alcoholism. In our previous results, SAL was reported to have the mutagenicity and clastogenicity not in bacteria but in mammalian cells, and its genotoxic potential was known to be potentiated in the presence of rat liver S-9 fraction. This may indicate that some metabolite(s) of SAL was involved in the mutagenic potentials. To investigate the SAL metabolites, the metabolism studies of SAL were conducted in vitro rat liver S-9 fraction and in vivo using rats by high performance liquid chromatography and gas chromatography/mass spectrometry. The methylated metabolite of SAL was found in urine of rats, while the same methylating form of metabolite was not produced from the in vitro metabolism system using rat liver S-9 fraction.

• Biomolecules & Therapeutics
• /
• 제9권2호
• /
• pp.88-95
• /
• 2001

(+)-Methamphetamine (METH) is a psychostimulant, which has been the most popular abused drug in Korea. The rewarding mechanism in METH abuse has been reported to be mediated by dopaminergic system. Recently, it has been reported that dopamine releaser (phentermine) plays a dominant role in the discriminative stimulus effects of METH, whereas 5-HT releaser (fenfluramine) can strongly modify METH self-administration. The present study is designed to assess the behavioral changes and the changes of the serotonin receptors in the brains of rats administered repeated of self-administered METH. The repeated administration of 1.0 mg/kg/day METH for 12 days increased locomotor activities, and there was no difference between i.v. and i.p. treatment. Rats had actively acquired METH self-administration for 3 weeks at 0.1 or 0.2 mg/kg/injection. Whereas, it was taken few days to acquire sucrose pellet self-administration. The binding of [$^3$H]-8-hydroxy-DPAT (5-H $T_{1A}$ receptors) and [$^3$H]-5-carboxytryptamine (5-H $T_{1B}$ receptors) to brain sections was examined. Both passive administration and self-administration of METH did not change significantly the serotonin receptors levels in hippocampus, striatum and nucleus accumbens. These results suggest that serotonin receptors may not change in the acquisition period of METH self-administration, and we are trying to investigate the serotonin receptors levels of brain in rats maintained of METH self-administration.n.n.