1.Delay in Normalization of Disrupted Sleep-Wake Cycle in Mice as a Bipolar Disorder-Prone Animal Model (Bipolar Disorder-Prone Animal Model).
Soo Yeon KIM ; Eunsoo MOON ; Hee Jeong JEONG ; Young Min LEE ; Byung Dae LEE ; Je Min PARK
Journal of Korean Neuropsychiatric Association 2016;55(3):209-214
OBJECTIVES: This study was designed to test the hypothesis that delayed recovery from disrupted circadian rhythm is associated with both manic and depressive episodes in bipolar disorder. METHODS: Twenty-two male mice (age of five weeks, weight 28–30 gm) underwent three days of light-dark cycle disruption and 10 days of recovery phase. Sleep and wake state were checked every five minutes during the entire experimental period. After recovery phase, quinpirole (0.5 mg/kg, s.c.) was injected into the mice and open field locomotor activities were checked. Five days after the open field test, immobility time during the last 4 min in 6 min of forced swimming test was measured. Animals which recovered sleep-wake cycle within six days after light-dark cycle disruption were assigned to the early recovery group (n=14), and those that failed to recover in six days were assigned to the delayed recovery group (n=8). The locomotor activities and the immobility times of the two groups were compared by Mann-Whiney U test at two-tailed significance level of 0.05. RESULTS: The locomotor activities of the delayed recovery group were higher (mean rank=16.19) than those of the early recovery group (mean rank=8.82, U=18.5, p=0.008). The immobility times did not differ by recovery time (U=32.0 p=0.110). CONCLUSION: The results suggest that delayed recovery from circadian rhythm disruption raises the risk of manic symptoms rather than depressive symptoms.
Animals
;
Animals*
;
Bipolar Disorder
;
Circadian Rhythm
;
Depression
;
Humans
;
Male
;
Mice*
;
Models, Animal*
;
Motor Activity
;
Photoperiod
;
Physical Exertion
;
Quinpirole
2.Delay in the Recovery of Normal Sleep-Wake Cycle after Disruption of the Light-Dark Cycle in Mice: A Bipolar Disorder-Prone Animal Model?.
Sun Hwa JUNG ; Je Min PARK ; Eunsoo MOON ; Young In CHUNG ; Byung Dae LEE ; Young Min LEE ; Ji Hoon KIM ; Soo Yeon KIM ; Hee Jeong JEONG
Psychiatry Investigation 2014;11(4):487-491
OBJECTIVE: Disruption of the circadian rhythm is known as a provoking factor for manic episodes. Individual differences exist in the recovery rate from disruption in the general population. To develop a screening method to detect individuals vulnerable to bipolar disorder, the authors observed the relationship between the recovery of the normal sleep-wake cycle after switching the light-dark (LD) cycle and quinpirole-induced hyperactivity in mice. METHODS: Sixteen male mice (age of 5 weeks, weight 28-29 gm) were subjected to a circadian rhythm disruption protocol. Sleep-wake behaviors were checked every 5 min for a total duration of 15 days, i.e., 2 days of baseline observations, 3 days of LD cycle changes, and 10 days of recovery. During the dark cycle on the 16th experimental day, their general locomotor activities were measured in an open field for 120 minutes after an injection of quinpirole (0.5 mg/kg, s.c.). RESULTS: The individual differences in the recovery rate of the baseline sleep-wake cycle were noted after 3 days of switching the LD cycle. Fifty percent (n=8) of the mice returned to the baseline cycle within 6 days after normalizing the LD cycle (early recovery group). The locomotor activities of mice that failed to recover within 6 days (delayed recovery group) were significantly higher (mean rank=12.25) than those of the early recovery group (mean rank=4.75, u=62.0, p=0.001, Mann-Whitney U test). CONCLUSION: Given that the quinpirole-induced hyperactivity is an animal model of bipolar disorder, our results suggest individuals who have difficulties in recovery from circadian rhythm disruption may be vulnerable to bipolar disorder.
Animals
;
Bipolar Disorder
;
Circadian Rhythm
;
Humans
;
Individuality
;
Male
;
Mass Screening
;
Mice*
;
Models, Animal*
;
Motor Activity
;
Photoperiod*
;
Quinpirole
3.Interactions of Dopamine D1 and N-methyl-D-Aspartate Receptors are Required for Acute Cocaine-Evoked Nitric Oxide Efflux in the Dorsal Striatum.
Dong Kun LEE ; Sung Min AHN ; Yoon Bo SHIM ; Wei Choon Alvin KOH ; Insop SHIM ; Eun Sang CHOE
Experimental Neurobiology 2011;20(2):116-122
Alterations in nitric oxide (NO) release in response to psychostimulants in the striatum cause a plastic change contributing to the development and expression of addiction. In this study, regulation of NO efflux evoked by acute cocaine in the dorsal striatum was investigated using real-time detection of NO in vivo. We found that acute systemic injection of cocaine (20 mg/kg) increased NO efflux, which was reduced by the intrastriatal infusion of the dopamine D1 receptor antagonist, SCH23390 (7.5 nmol), and the dopamine D2 receptor agonist, quinpirole (5 nmol). Increased levels of NO efflux by acute cocaine were also reduced by the intrastriatal infusion of the N-methyl-D-aspartate (NMDA) receptor antagonists, MK801 (2 nmol) and AP5 (2 nmol). These findings suggest that interactions of dopamine D1 receptors and NMDA receptors after acute exposure to cocaine participate in the upregulation of NO efflux in the dorsal striatum.
Benzazepines
;
Cocaine
;
Dizocilpine Maleate
;
Dopamine
;
Glutamic Acid
;
N-Methylaspartate
;
Nitric Oxide
;
Plastics
;
Quinpirole
;
Receptors, Dopamine D1
;
Receptors, Dopamine D2
;
Receptors, N-Methyl-D-Aspartate
;
Up-Regulation
4.Protein Kinase C Activity and Delayed Recovery of Sleep-Wake Cycle in Mouse Model of Bipolar Disorder.
Eunsoo MOON ; Byeong Moo CHOE ; Je Min PARK ; Young In CHUNG ; Byung Dae LEE ; Jae Hong PARK ; Young Min LEE ; Hee Jeong JEONG ; YongJun CHEON ; Yoonmi CHOI ; Jeonghyun PARK
Psychiatry Investigation 2018;15(9):907-913
OBJECTIVE: Previous studies reported the delayed recovery group after circadian rhythm disruption in mice showed higher quinpiroleinduced locomotor activity. This study aimed to compare not only Protein Kinase C (PKC) activities in frontal, striatal, hippocampus and cerebellum, but also relative PKC activity ratios among brain regions according to recovery of circadian rhythm. METHODS: The circadian rhythm disruption protocol was applied to eight-week-old twenty male Institute Cancer Research mice. The circadian rhythm recovery patterns were collected through motor activities measured by Mlog system. Depressive and manic proneness were examined by forced swim test and quinpirole-induced open field test respectively. Enzyme-linked immunosorbent assay was employed to measure PKC activities. RESULTS: The delayed recovery group presented greater locomotor activities than the early recovery group (p=0.033). The delayed recovery group had significantly lower frontal PKC activity than the other (p=0.041). The former showed lower frontal/cerebellar PKC activity ratio (p=0.047) but higher striatal/frontal (p=0.038) and hippocampal/frontal (p=0.007) PKC activities ratios than the latter. CONCLUSION: These findings support potential mechanism of delayed recovery after circadian disruption in bipolar animal model could be an alteration of relative PKC activities among mood regulation related brain regions. It is required to investigate the PKC downstream signaling related to the delayed recovery pattern.
Animals
;
Bipolar Disorder*
;
Brain
;
Cerebellum
;
Circadian Rhythm
;
Enzyme-Linked Immunosorbent Assay
;
Hippocampus
;
Humans
;
Male
;
Mice*
;
Models, Animal
;
Motor Activity
;
Protein Kinase C*
;
Protein Kinases*
;
Quinpirole
5.Increased Burst Firing in Substantia Nigra Pars Reticulata Neurons and Enhanced Response to Selective D2 Agonist in Hemiparkinsonian Rats After Repeated Administration of Apomorphine.
Jung Il LEE ; Hee Jung SHIN ; Do Hyun NAM ; Jong Soo KIM ; Seung Chyul HONG ; Hyung Jin SHIN ; Kwan PARK ; Whan EOH ; Jong Hyun KIM ; Won Yong LEE
Journal of Korean Medical Science 2001;16(5):636-642
Intermittent administrations of dopaminergic agents in hemiparkinsonian rat enhances the behavioral response to subsequent administration of the drugs. This phenomenon is known as "priming" and thought as comparable to drug-induced dyskinesia in patients with Parkinson's disease. We investigated the behavioral and electrophysiological changes in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats after repeated administrations of apomorphine. Administration of apomorphine (0.32 mg/kg, intraperitoneal, i.p.) twice daily for 6 days enhanced the rotation induced by apomorphine from 341 turns/hour at the beginning to 755 turns/hr at the end. At the same time, the response to selective D2 agonist quinpirole (0.26 mg/kg, i.p.) was also enhanced from 203 to 555 turns/hr. Extracellular single unit recording revealed no significant difference in the basal firing rates of substantia nigra pars reticulata (SNr) neurons between the ipsilateral and contralateral side of the 6-OHDA lesion regardless of the repeated administrations of apomorphine. In SNr of the lesion side, the units with burst firing pattern were found more frequently after repeated administrations of apomorphine and the suppressive effect of quinpirole on the firing rate was enhanced. These findings suggest that the increased percentage of the burst units is the important electrophysiological change in the development of enhanced response to selective D2 agonist.
Animal
;
Apomorphine/*pharmacology
;
Dopamine Agonists/*pharmacology
;
MPTP Poisoning/physiopathology
;
Male
;
Oxidopamine/toxicity
;
Parkinsonian Disorders/*physiopathology
;
Quinpirole/pharmacology
;
Rats
;
Rats, Sprague-Dawley
;
Receptors, Dopamine D2/*drug effects
;
Substantia Nigra/*drug effects/physiology
6.Quinpirole Increases Melatonin-Augmented Pentobarbital Sleep via Cortical ERK, p38 MAPK, and PKC in Mice.
Sa Ik HONG ; Seung Hwan KWON ; Ji Young HWANG ; Shi Xun MA ; Jee Yeon SEO ; Yong Hyun KO ; Hyoung Chun KIM ; Seok Yong LEE ; Choon Gon JANG
Biomolecules & Therapeutics 2016;24(2):115-122
Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2-like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital-induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantly. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findings suggest that modulation of D2-like receptors might enhance the effect of MT on sleep.
Animals
;
Cerebral Cortex
;
Cyclic AMP-Dependent Protein Kinases
;
Dopamine
;
gamma-Aminobutyric Acid
;
Humans
;
Hypnotics and Sedatives
;
Melatonin
;
Mice*
;
Mitogen-Activated Protein Kinases
;
Motor Activity
;
Neurotransmitter Agents
;
p38 Mitogen-Activated Protein Kinases*
;
Pentobarbital*
;
Phosphotransferases
;
Protein Kinase C
;
Protein Kinases
;
Quinpirole*
7.Differential DAergic Control of D1 and D2 Receptor Agonist Over Locomotor Activity and GABA Level in the Striatum.
Experimental Neurobiology 2011;20(3):153-157
The basal ganglia, a group of nuclei, are associated with a variety of functions, including motor control. The striatum, which is the major input station of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. The striatum is made up 96% of medium spiny neurons which are GABAergic cells. GABAergic cells are known to contain DA receptors which divide into two main branches- the D1 receptor (D1R)-expressing direct pathway and the D2 receptor (D2R)-expressing indirect pathway. The role of these two efferent pathways has not been clear in control of motor behaviors. To establish the influence of the different DA subtypes on GABAergic systems in the striatum, D1 selective receptor agonist (SKF 38393) and D2 selective receptor agonist (Quinpirole) were administered to mice. SKF 38393 and quinpirole were administered intraperitoneally in a volume of 0, 1, 5, 10 (mg/kg) and motor activity was assessed for 60 min immediately after the injection of DA agonists. Mice were sacrificed after behavioral test and the striatum in the brain were dissected for analysis of GABA level with HPLC. Both SKF 38393 and quinpirole dose-dependently increased locomotor activity but, GABA level in the striatum was clearly different in two agonists. These findings provide insight into the selective contributions of the direct and indirect pathways to striatal GABAergic motor behaviors.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
;
Animals
;
Basal Ganglia
;
Brain
;
Chromatography, High Pressure Liquid
;
Efferent Pathways
;
gamma-Aminobutyric Acid
;
Mice
;
Motor Activity
;
Neurons
;
Quinpirole
;
Substantia Nigra
8.Lesion of Subthalamic Nucleus in Parkinsonian Rats: Effects of Dopamine D1 and D2 Receptor Agonists on the Neuronal Activities of the Substantia Nigra Pars Reticulata.
Yong Sook PARK ; Mi Fa JEON ; Bae Hwan LEE ; Jin Woo CHANG
Journal of Korean Neurosurgical Society 2007;42(6):455-461
OBJECTIVE: It was hypothesized that dopamine agonist administration and subthalamic nucleus (STN) lesion in the rat might have a synergistic effect on the neuronal activities of substantia nigra pars reticulata (SNpr) as observed in patients with Parkinson's disease. The effects of SKF38393 (a D1 receptor agonist) and Quinpirole (a D2 receptor agonist) were compared in parkinsonian rat models with 6- hydroxydopamine (6-OHDA) after STN lesion. METHODS: SKF38393 and Quinpirole were consecutively injected intrastriatally. SNpr was microrecorded to ascertain the activity of the basal ganglia output structure. The effect of SKF38393 or Quinpirole injection on the firing rate and firing patterns of SNpr was investigated in medial forebrain bundle (MFB) lesioned rats and in MFB+STN lesioned rats. RESULTS: The administration of SKF38393 decreased SNpr neuronal firing rates and the percentage of burst neurons in the MFB lesioned rats, but did not alter them in MFB+STN lesioned rats. The administration of Quinpirole significantly decreased the spontaneous firing rate in the MFB lesioned rats. However, after an additional STN lesion, it increased the percentage of burst neurons. CONCLUSION: This study demonstrated that dopamine agonists and STN lesion decreased the hyperactive firing rate and the percentage of burst neurons of SNpr neurons in 6-OHDA lesioned rats, respectively. Quinpirole with STN lesion increased a percentage of burst neurons. To clear the exact interactive mechanism of D1 and D2 agonist and the corresponding location, it should be followed a study using a nonselective dopamine agonist and D1, D2 selective antagonist.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
;
Animals
;
Basal Ganglia
;
Dopamine Agonists
;
Dopamine*
;
Fires
;
Humans
;
Hydroxydopamines
;
Kainic Acid
;
Medial Forebrain Bundle
;
Models, Animal
;
Neurons*
;
Oxidopamine
;
Parkinson Disease
;
Quinpirole
;
Rats*
;
Substantia Nigra*
;
Subthalamic Nucleus*
9.Gap Junction Contributions to the Goldfish Electroretinogram at the Photopic Illumination Level.
The Korean Journal of Physiology and Pharmacology 2012;16(3):219-224
Understanding how the b-wave of the electroretinogram (ERG) is generated by full-field light stimulation is still a challenge in visual neuroscience. To understand more about the origin of the b-wave, we studied the contributions of gap junctions to the ERG b-wave. Many types of retinal neurons are connected to similar and different neighboring neurons through gap junctions. The photopic (cone-dominated) ERG, stimulated by a small light beam, was recorded from goldfish (Carassius auratus) using a corneal electrode. Data were obtained before and after intravitreal injection of agents into the eye under a photopic illumination level. Several agents were used to affect gap junctions, such as dopamine D1 and D2 receptor agonists and antagonists, a nitric oxide (NO) donor, a nitric oxide synthase (NOS) inhibitor, the gap junction blocker meclofenamic acid (MFA), and mixtures of these agents. The ERG b-waves, which were enhanced by MFA, sodium nitroprusside (SNP), SKF 38393, and sulpiride, remained following application of a further injection of a mixture with MFA. The ERG b-waves decreased following NG-nitro-L-arginine methyl ester (L-NAME), SCH 23390, and quinpirole administration but were enhanced by further injection of a mixture with MFA. These results indicate that gap junction activity influences b-waves of the ERG related to NO and dopamine actions.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
;
Benzazepines
;
Dopamine
;
Electrodes
;
Eye
;
Gap Junctions
;
Goldfish
;
Humans
;
Intravitreal Injections
;
Light
;
Lighting
;
Meclofenamic Acid
;
Neurons
;
Neurosciences
;
NG-Nitroarginine Methyl Ester
;
Nitric Oxide
;
Nitric Oxide Synthase
;
Nitroprusside
;
Quinpirole
;
Retinal Neurons
;
Sulpiride
;
Tissue Donors