The authors examined the specificity of the dopamine-2 receptor for eyeball growth of the experimental myopic chicken eyes. Two day-old white Leghorn chickens were monocularly deprived of vision by lid suture of the right eyes. We measured the axial lengths of chicken's eyes by ultrasonography at the 2nd day and the 4th weeks. The right eyes of the first group were instillated with 0.04cc of tris buffer solution, those of the second and third group were instillated with 0.04cc of 0.02% SKF38393 hydrochloride solution and 0.02% bromocriptine solution individually. All solutions were instillated into the right eyes two times per day during 4 weeks. At the 2nd day of the age, the axial lengths of the first group's eyeballs were 7.83 +/- 0.14mm in the right, 7.87 +/- 0.15mm in the left eyes, 7.78 +/- 0.16mm in the right eyes, 7.77 +/- 0.11mm in the left eyes of the second group and 7.89 +/- 0.12mm in the right eyes, 7.87 +/- 0.12mm in the left eyes of the third group. Each group was not statistically different (p>0.05). But at the four weeks of the age, the axial lengths of the lid sutured right chicken eyeball were 11.39 +/- 0.27mm in the first group, 11.40 +/- 0.40mm in the second group and 11.20 +/- 0.40mm in the third group, The third group was statistically different from the first or 2nd group (p<0.05). The growth of the axial lengths of the right chicken eyeballs from the 2nd day to the 4th week of the age was 3.50 +/- 0.35mm in the first, 3.63 +/- 0.42mm in the second and 3.21 +/- 0.29mm in the third group. The right eyes of the third group were found significantly less growth than those of other groups. These results suggest that dopamine-2 receptor playa role in eyeball growth.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine ; Bromocriptine ; Chickens* ; Myopia* ; Sensitivity and Specificity* ; Sutures ; Tromethamine ; Ultrasonography

BACKGROUND: The selective D1 dopamine agonist has been known to play a stimulatory role in substance-P synthesis in the striatum, but its effect on the enkephalin mRNA expression has not been well known in the striatum of unilateral 6-hydroxydopamine(OHDA)-lesioned rat. So we investigated the effect of selective D1 dopaminergic agonist on substance-P, enkephalin mRNA expression in the striatum with different time interval. METHODS: The lesioned rats were divided into two groups (treated and non-treated). Each group was subdivided according to time course after lesioning (2nd, 4th and 8th week). Dopamine 1 receptor agonist, SKF-38393 (5 mg/kg/ip) and the same volume of saline was injected to treated and nontreated group respectively. The levels of enkephalin and substance-P mRNA were determined by in situ-hydridization and the expression of mRNA levels were compared between the groups. RESULTS: The expression of striatal enkephalin mRNA was increased on lesioned side in all groups. Especially, SKF-38393 enhanced the striatal expression of enkephalin mRNA after lesioning 2nd week. After lesioning 4th week and 8th week, the effect of SKF-38393 was not significant. The striatal expression of substance-P mRNAs was significantly decreased on the lesioned side, especially at the 2nd weeks. This decrement of substance-P mRNA was reversed by SKF-38393 at the 2nd week. CONCLUSIONS: These data show that the selective D1 agonist SKF-38393 have an agonistic effect on direct pathway but antagonistic effect on indirect pathway in early course of Parkinsonian rat model.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine ; Animals ; Dopamine ; Dopamine Agonists ; Enkephalins* ; Models, Animal* ; Rats* ; RNA, Messenger*

BACKGROUND: The selective D1 dopamine agonist has been known to play a stimulatory role in substance-P synthesis in the striatum, but its effect on the enkephalin mRNA expression has not been well known in the striatum of unilateral 6-hydroxydopamine(OHDA)-lesioned rat. So we investigated the effect of selective D1 dopaminergic agonist on substance-P, enkephalin mRNA expression in the striatum with different time interval. METHODS: The lesioned rats were divided into two groups (treated and non-treated). Each group was subdivided according to time course after lesioning (2nd, 4th and 8th week). Dopamine 1 receptor agonist, SKF-38393 (5 mg/kg/ip) and the same volume of saline was injected to treated and nontreated group respectively. The levels of enkephalin and substance-P mRNA were determined by in situ-hydridization and the expression of mRNA levels were compared between the groups. RESULTS: The expression of striatal enkephalin mRNA was increased on lesioned side in all groups. Especially, SKF-38393 enhanced the striatal expression of enkephalin mRNA after lesioning 2nd week. After lesioning 4th week and 8th week, the effect of SKF-38393 was not significant. The striatal expression of substance-P mRNAs was significantly decreased on the lesioned side, especially at the 2nd weeks. This decrement of substance-P mRNA was reversed by SKF-38393 at the 2nd week. CONCLUSIONS: These data show that the selective D1 agonist SKF-38393 have an agonistic effect on direct pathway but antagonistic effect on indirect pathway in early course of Parkinsonian rat model.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine ; Animals ; Dopamine ; Dopamine Agonists ; Enkephalins* ; Models, Animal* ; Rats* ; RNA, Messenger*

BACKGROUND & OBJECTIVES: Glutamate is a major neurotrammitter in corticostriatal, subthalamopallidal, and subthalamonigral pathways and interacts with other neurotrammitters. The study was done to investigate the effects of NMDA blockade on dopaminergic responses. METHODS: We made a unilateral Parkinson model in rats by injecting 6-hydroxydopamine into the substantia nigra. Rotational behavior was observed using apomorphine (mixed Dl/D2 agonist, 0. 5 mg/kg), SKF 38393 (Dl agonist, 1. 5 mg/kg), LY-171555 (D2 agonist, 0. I mg/kg), MK-801 (uncompetitive NMDA blocker, 0. 067 mg/kg), and memantine (non competitive NMDA blocker, 10 mg/kg). RESULTS: Contralateral rotation was induced by apomorphine (total turns for 2 hours, 1160+/-154), SKF 38393 (total turns for 3 hours, 1374+/-400), and LY 171555 (total turns for 3 hours 2316+/-395). NMDA antagonists per se induced mild ipsilateral rotation (MK 801; 587+/-131, memantine; 166+36). Apomorphine induced rotation was potentiated by MK 801 (1683+/-186, p<0.05) and memantine (170+/-264, p<0.05). SKF 38393 induced rotation tended to be potetiated by MK-801 (2451+/-741, p=0.08) and memantine (1794+/-450, p=0.21), though not statistically significant. However, LY 171555 induced rotation was reduced by MK-801 (1153+/-284, p<0.05) ad memantine (22.1+/-42.5, p<0.05). CONCLUSION: NMDA blockers act synergistically with Dl- and antagonistically with D2-mediated behavioural responses, suggesting that glutamate has different interactions with Dl- and D2 pathway.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine ; Animals ; Apomorphine ; Dizocilpine Maleate ; Glutamic Acid ; Hydroxydopamines* ; Memantine ; N-Methylaspartate* ; Oxidopamine ; Rats* ; Substantia Nigra

The present study was aimed to explore the involvement of dopamine D1 receptor of the anterior cingulate cortex (ACC) in the regulation of chronic inflammatory pain-related emotion. On the first day, the rats were acclimated to the environment and the baseline indices were measured. On the second day, the rats were administered with the dopamine D1 receptor antagonist SCH-23390 or agonist SKF38393 in the ACC, and then they were subcutaneously injected with complete Freund's adjuvant (CFA, 0.08 mL) in the left hind paw to establish conditioned place avoidance (CPA) response after pairing with specific environment. On the third day, the CPA response and the firing frequency of ACC neurons were observed synchronously, and the open-field behavior, mechanical pain behavior and paw withdrawal latency (PWL) tests were also observed subsequently. In other experiments, rats were given subcutaneous injection of normal saline (NS) on the left hind paw after SCH-23390 or SKF-38393 was administered in the ACC, and then the same observations were performed. The results showed that: (1) Compared with the control group, the PWL and mechanical pain thresholds of rats injected with CFA on the left hind paw were significantly decreased (P < 0.05); (2) The residence time of rats injected with CFA in the "pain environment" and open field center was significantly shortened (P < 0.05); (3) Pre-injection of antagonist SCH-23390 in ACC (10 μg) alleviated the anxiety-like negative behavior response induced by CFA (P < 0.05) and reversed CFA-induced increases of discharge frequency of ACC neurons (P < 0.05); (4) Pre-injection of agonist SKF-38393 in the ACC (10 μg) induced CPA-like behavioral response in rats injected with NS in the left hind paw, and increased the firing frequency of ACC neurons (P < 0.05); (5) Immunofluorescence detection showed that dopamine D1 receptor and NMDA receptor were co-expressed in the same neuron. These results suggest that inhibition of dopamine D1 receptor in ACC can alleviate the negative emotional response induced by persistent pain.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/adverse effects* ; Animals ; Anxiety ; Chronic Pain ; Gyrus Cinguli ; Hyperalgesia ; Rats ; Receptors, Dopamine D1/metabolism*

OBJECTIVES: It was aimed to observe the regional cerebral blood flow (rCBF) response on methamphetamine challenge test in rats which were subjected to repeated administration of methamphetamine, and to investigate the mechanism(s) of changes in rCBF response in relation to the dopaminergic receptors and cyclic AMP. METHODS: Male Sprague-Dawley rats received daily injections of methamphetamine (0.3 mg/kg, i.p.) for 10 days, and were then allowed a 4-day drug-free period. Naive and methamphetamine-pretreated rats were challenged with topical application of methamphetamine on the surface of parietal cortex through a cranial window. The changes in rCBF were measured by laser-Doppler flowmetry. RESULTS: Acute topical application of methamphetamine dose-dependently increased rCBF with little effect on mean arterial blood pressure. The methamphetamine-induced increases in rCBF were significantly blocked by SCH23390, a D1-like receptor antagonist, but not by sulpiride, a D2-like receptor antagonist. Repeated administration of methamphetamine induced progressive augmentation of rCBF in response to the challenge of methamphetamine. Repeated administration of methamphetamine in combination with SKF38393, a D1-like receptor agonist, as well as with SCH23390 significantly attenuated the development of augmentation of rCBF response to methamphetamine. The augmentation of rCBF response was markedly inhibited by pretreatment with 2',3'-dideoxyadenosine, a specific adenylyl cyclase inhibitor, and Rp-cAMPS, a protein kinase A inhibitor, respectively. CONCLUSION: Based on these results, it is suggested that repeated administration of methamphetamine induces an augmentation of rCBF in response to the challenge of methamphetamine, and that D1-like receptor-mediated cyclic AMP plays a critical role in the development of augmentation of methamphetamine-induced rCBF response.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine ; Adenylyl Cyclases ; Animals ; Arterial Pressure ; Cyclic AMP ; Cyclic AMP-Dependent Protein Kinases ; Dideoxyadenosine ; Humans ; Laser-Doppler Flowmetry ; Male ; Methamphetamine* ; Rabeprazole ; Rats* ; Rats, Sprague-Dawley ; Sulpiride

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*

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

OBJECTIVETo explore the possible differential trafficking properties of the dopamine D1-like receptor subtypes, D1 receptor and D5 receptor.

METHODSTo visualize distributions of dopamine D1-like receptor subtypes at subcellular level, the yellow and cyan variants of green fluorescent protein (GFP) were used to tag D1 and D5 receptors. After transfection with the tagged dopamine receptors, the neuroblastoma cells NG108-15 were treated with D1 agonist SKF38393 or acetylcholine (ACh). Then we observed the subcellular distributions of the tagged receptors under the confocal microscopy and tried to determine trafficking properties by comparing their distribution patterns before and after the drug treatment.

RESULTSIn resting conditions, D1 receptors located in the plasma membrane of NG108-15 cells, while D5 receptors located in both plasma membrane and cytosol. With the pre-treatment of SKF38393, the subcellular distribution of D1 receptors was changed. The yellow particle-like fluorescence of tagged D1 receptors appeared in the cytosol, indicating that D1 receptors were internalized into cytosol from the cell surface. Same situation also occurred in ACh pre-treatment. In contrast, the subcellular distribution of D5 receptors was not changed after SKF38393 or ACh treatment, indicating that D5R was not translocated to cell surface. Interestingly, when D1 and D5 receptors were co-expressed in the same cell, both kept their distinct subcellular distribution patterns and the trafficking properties.

CONCLUSIONOur present study reveals that in NG108-15 nerve cells, dopamine D1 and D5 receptors exhibit differential subcellular distribution patterns, and only D1 receptor has a marked trafficking response to the drug stimulation. We further discuss the potential role of the differential trafficking properties of D1-like receptors in complex modulation of DA signaling.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine ; pharmacology ; Acetylcholine ; pharmacology ; Animals ; Cell Line ; Dopamine Agonists ; pharmacology ; HeLa Cells ; Humans ; Luminescent Proteins ; genetics ; Mice ; Microscopy, Confocal ; methods ; Neuroblastoma ; Protein Transport ; drug effects ; Rats ; Receptors, Dopamine D1 ; metabolism ; Receptors, Dopamine D5 ; metabolism ; Subcellular Fractions ; metabolism ; ultrastructure ; Transfection ; methods

The present study was to investigate the role of dopamine D1 receptors and its relationship with glutamate, N-methyl-D-aspartic acid (NMDA) receptor and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor in depression induced by chronic unpredictable mild stress (CUMS). CUMS-induced depression model was established in Sprague-Dawley rats, and intrahippocampal microinjections of D1 dopamine receptor agonist SKF38393, non-competitive NMDA receptor antagonist MK-801 and AMPA receptor antagonist NBQX were respectively adopted by rat brain stereotaxic coordinates. The behavioral observations were conducted by measurement of weight changes, sucrose preference test, open-field test and tail suspension test. The concentration of glutamic acid and the expression of its receptors' subunits were detected by HPLC and Western blot, respectively. The results showed that, compared with control group, CUMS rats showed depression-like behavioral changes, higher concentration of glutamic acid, lower expressions of NMDA receptor (NR1) and AMPA receptor (GluR2/3) in hippocampus. Pretreatment with injection of SKF38393 could rescue such depression effect of CUMS, decrease the concentration of glutamic acid, and increase the expressions of NMDA receptor (NR1), AMPA receptor (GluR2/3) in hippocampus. Pretreatment with MK-801 could enhance the antidepressant effect of SKF38393, while NBQX weakened. These results suggest that agonists of D1 dopamine receptor could reduce the concentration of glutamic acid in hippocampus, and its antidepressant effect may be mediated by AMPA receptor partially.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine ; pharmacology ; Animals ; Depression ; etiology ; physiopathology ; Dizocilpine Maleate ; pharmacology ; Excitatory Amino Acid Antagonists ; Glutamates ; metabolism ; Hippocampus ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA ; metabolism ; Receptors, Dopamine D1 ; agonists ; physiology ; Stress, Physiological ; physiology