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1.
Front Neurol ; 13: 928803, 2022.
Article in English | MEDLINE | ID: mdl-35911880

ABSTRACT

Pregnancy-associated cervicocephalic arterial dissection is rare, and its pathophysiology remains poorly understood. Despite the hypothesized contribution to pathogenesis, connective tissue diseases and genetic factors are rarely identified in clinical cases. We describe a case of postpartum arterial dissection involving all four cervicocephalic arteries resulting in acute cerebral infarction. The patient underwent successful endovascular thrombectomy and angioplasty and recovered fully without sequelae. Genetic screening for connective tissue diseases identified a heterozygous missense COL5A1 variant with unknown clinical significance. Two genetically related family members later developed arterial abnormalities, and one of them tested positive for the same COL5A1 gene variant as our patient, while the other was scheduled for genetic testing. The extensive clinical presentation of our patient and the prevalence of arterial abnormalities in her family warrant further assessment of the association between the identified COL5A1 gene variant and the pathogenesis of arterial dissections.

2.
Medicine (Baltimore) ; 94(1): e268, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25569642

ABSTRACT

Previous reports demonstrated 8-60% patients treated for developmental dislocation of hip (DDH) in infancy have residual acetabular dysplasia (AD) at skeletal maturity. AD patients reportedly exhibit abnormal morphology of the pelvis, high rates of comorbid spinal congenital anomalies and high bone mineral density. These physical findings suggest that AD patients have genetic background. We examined the percentage of AD patients with hip pain at skeletal maturity having a history of DDH in infancy and the correlation between the severity of AD at skeletal maturity and history of DDH treatment to investigate the relationship between AD and DDH.A total of 245 patients were radiographically examined for any history of DDH treatment in infancy. The study included 226 women and 19 men with a mean age at examination of 40.7 years (range 17-59 years).Eighty-eight patients (36%) had a history of DDH treatment (DDH group) and the remaining 157 patients (64%) had no history of DDH treatment (non-DDH group). The average age was lower and acetabular angle was larger in the DDH group. There was a significant increasing trend of the percentage of DDH patients associated with the severity of AD classified with CE, acetabular angle, and acetabular roof angle.Our data suggest that there are several AD patients without a history of DDH in Japan, and AD in patients without a history of DDH has different characteristics from AD in patients with a history of DDH.


Subject(s)
Hip Dislocation/etiology , Osteoarthritis, Hip/etiology , Adolescent , Adult , Female , Humans , Infant, Newborn , Male , Middle Aged , Retrospective Studies , Young Adult
3.
Mod Rheumatol ; 24(2): 340-2, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24593210

ABSTRACT

OBJECTIVE: Increased femoral neck bone mineral density (BMD) in a hip with osteoarthritis (OA) has been previously reported, however, it is possible that increased BMD at sites other than the hip joint is influenced by the disease process of OA. Therefore, we measured BMD at locations different from the hip joint and determined whether higher BMD was also observed at these different skeletal sites in hip OA patients. METHODS: We measured BMD in 68 women (average age 61.0 years) scheduled to undergo total hip arthroplasty for end-stage OA and 100 healthy women (average age 60.9 years) as age-matched controls. BMD at the lumbar spine, radius, and calcaneus was measured by dual-energy X-ray absorptiometry (DXA). Moreover, we measured speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index of the calcaneus by quantitative ultrasonography (QUS). RESULTS: BMD obtained by DXA at the lumbar spine and radius was significantly higher in hip OA patients than in controls. However, at the calcaneus, no significant differences were observed between the groups in BMD obtained by DXA. SOS, BUA, and stiffness index obtained by QUS were significantly lower in the OA group than in controls. CONCLUSION: Higher BMDs of the spine and radius suggest that the incidence of osteoporosis is inversely associated with the incidence of OA. However, it remains unclear whether lack of difference in BMD and lower SOS, BUA, and stiffness index of the calcaneus in the OA group was secondary to the effect walking disturbance resulting from hip pain. Our data suggest that hip OA patients have higher BMD than healthy women, and that inactivity or immobilization caused by hip OA may reduce BMD in the lower limb.


Subject(s)
Bone Density/physiology , Calcaneus/diagnostic imaging , Lumbar Vertebrae/diagnostic imaging , Osteoarthritis, Hip/diagnostic imaging , Radius/diagnostic imaging , Aged , Female , Humans , Middle Aged , Radiography
4.
Med Sci Monit ; 20: 116-22, 2014 Jan 26.
Article in English | MEDLINE | ID: mdl-24463880

ABSTRACT

BACKGROUND: Acetabular dysplasia (AD) is the main cause of hip osteoarthritis in Japan. A simple method to evaluate acetabular dysplasia would be helpful for early treatment or prevention of hip osteoarthritis. Acetabular dysplasia is reported to be associated with pathological transverse growth of the pelvis, indicating that the distance between the 2 anterior superior iliac spines might be useful for screening and detection of acetabular dysplasia. The purpose of this study was to determine if the acetabular dysplasia radiographic parameters are related to the distance between the 2 anterior superior iliac spines in patients with hip osteoarthritis. MATERIAL AND METHODS: In this study, data obtained in a previous multi-institutional examination of patients with hip osteoarthritis in Japan were evaluated. The anterior superior iliac spine distances of 176 female patients (mean age, 54 years; range, 18-85 years) were measured by physical examination. The relationship between the anterior superior iliac spine distance and acetabular dysplasia was analyzed, and the anterior superior iliac spine distances of the patients with acetabular dysplasia who were at relatively high risk for hip osteoarthritis were compared with that of the patients at lower risk. RESULTS: A statistically significant relationship between the anterior superior iliac spine distance and all of the acetabular dysplasia parameters was observed. The anterior superior iliac spine distances of the acetabular dysplasia patients with a relatively high risk for radiographic acetabular dysplasia parameters were significantly smaller than those of patients at lower risk. Even after adjustment for age, height, and weight, significantly increased relative risk for having high risk AD was found in patients with an ASIS distance of less than 24.5 cm. CONCLUSIONS: There was a significant relationship between the anterior superior iliac spine distance and the degree of acetabular dysplasia.


Subject(s)
Acetabulum/physiopathology , Bone Diseases, Developmental/complications , Bone Diseases, Developmental/diagnosis , Ilium/diagnostic imaging , Osteoarthritis, Hip/pathology , Biomarkers , Bone Diseases, Developmental/physiopathology , Female , Humans , Japan , Osteoarthritis, Hip/etiology , Radiography
5.
J Bone Miner Metab ; 32(3): 312-6, 2014 May.
Article in English | MEDLINE | ID: mdl-23921834

ABSTRACT

Recent reports have shown the existence of subchondral insufficiency fracture in rapidly destructive arthrosis of the hip joint (RDA), and the findings suggest that osteopenia is related to the pathogenesis of the rapid progression of this disease. Therefore, we measured bone mineral density (BMD) in RDA patients. We measured BMD of the lumbar spine, radius, and calcaneus using dual-energy X-ray absorptiometry in 19 patients with RDA and 75 with osteoarthritis of the hip (OA) and compared BMD at different skeletal sites between RDA and OA patients. No significant differences were observed in BMD of the lumbar spine, ultradistal radius, mid-radius, and calcaneous between the RDA and OA groups. Our data suggest that RDA is not accompanied by generalized osteoporosis. Factors other than generalized bone status, for example, BMD around the affected hip joint before destruction, need to be analyzed to elucidate the pathophysiological mechanism of RDA.


Subject(s)
Bone Density/physiology , Osteoarthritis, Hip/pathology , Absorptiometry, Photon/methods , Aged , Aged, 80 and over , Bone Diseases, Metabolic/diagnostic imaging , Bone Diseases, Metabolic/pathology , Calcaneus/diagnostic imaging , Calcaneus/pathology , Female , Hip/diagnostic imaging , Hip/pathology , Hip Joint/diagnostic imaging , Hip Joint/pathology , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/pathology , Middle Aged , Osteoarthritis, Hip/diagnostic imaging , Osteoporosis/diagnostic imaging , Osteoporosis/pathology
6.
Mod Rheumatol ; 2013 May 07.
Article in English | MEDLINE | ID: mdl-23649732

ABSTRACT

OBJECTIVE: Increased femoral neck bone mineral density (BMD) in a hip with osteoarthritis (OA) has been previously reported, however, it is possible that increased BMD at sites other than the hip joint is influenced by the disease process of OA. Therefore, we measured BMD at locations different from the hip joint and determined whether higher BMD was also observed at these different skeletal sites in hip OA patients. METHODS: We measured BMD in 68 women (average age 61.0 years) scheduled to undergo total hip arthroplasty for end-stage OA and 100 healthy women (average age 60.9 years) as age-matched controls. BMD at the lumbar spine, radius, and calcaneus was measured by dual-energy X-ray absorptiometry (DXA). Moreover, we measured speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index of the calcaneus by quantitative ultrasonography (QUS). RESULTS: BMD obtained by DXA at the lumbar spine and radius was significantly higher in hip OA patients than in controls. However, at the calcaneus, no significant differences were observed between the groups in BMD obtained by DXA. SOS, BUA, and stiffness index obtained by QUS were significantly lower in the OA group than in controls. CONCLUSION: Higher BMDs of the spine and radius suggest that the incidence of osteoporosis is inversely associated with the incidence of OA. However, it remains unclear whether lack of difference in BMD and lower SOS, BUA, and stiffness index of the calcaneus in the OA group was secondary to the effect walking disturbance resulting from hip pain. Our data suggest that hip OA patients have higher BMD than healthy women, and that inactivity or immobilization caused by hip OA may reduce BMD in the lower limb.

7.
Behav Brain Res ; 216(1): 46-52, 2011 Jan 01.
Article in English | MEDLINE | ID: mdl-20620171

ABSTRACT

Growing evidence indicates that the glutamatergic neurotransmitter system is central to the neurobiology and treatment of depression. Riluzole, a drug currently used to slow the progression of amyotrophic lateral sclerosis (ALS), directly affects the glutamatergic system. In this study, we investigated the effects of riluzole in olfactory bulbectomy (OBX) rats, an animal model of depression. The olfactory bulbs in rats were removed by suction. The emotionality of rats was measured by scoring their responses to given stimuli, i.e., attack, startle, struggle, and fight responses. The OBX rats chronically treated with vehicle for 7 days at 14 days following surgery showed significant increases in emotionality responses. Single (1st day administration) and subchronic (7th day administration) riluzole treatment (1-10 mg/kg, po) significantly and dose-dependently reduced hyperemotional responses in OBX rats. Both single and subchronic riluzole treatment (10 mg/kg, po) had no significant effects on the emotional responses in sham operated rats. In addition, we demonstrated that single riluzole treatment (10 mg/kg, po) significantly decreased extracellular glutamate levels in medial prefrontal cortex of OBX rats by in vivo microdialysis. We provide the first experimental evidence that riluzole rapidly attenuated hyperemotional responses in OBX rats, an animal model of depression.


Subject(s)
Depressive Disorder/drug therapy , Emotions/drug effects , Olfactory Bulb/surgery , Riluzole/pharmacology , Analysis of Variance , Animals , Behavior, Animal/drug effects , Chromatography, High Pressure Liquid , Disease Models, Animal , Glutamic Acid/metabolism , Male , Microdialysis , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Rats , Rats, Wistar , Riluzole/therapeutic use , Statistics, Nonparametric
8.
PLoS One ; 4(10): e7461, 2009 Oct 14.
Article in English | MEDLINE | ID: mdl-19829704

ABSTRACT

Recently, neurotrophic factors and cytokines have been shown to be associated in psychiatric disorders, such as schizophrenia, bipolar disorder, and depression. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family, serves as a neurotrophic molecular and plays a significant role in the brain. We generated mice in which HB-EGF activity is disrupted specifically in the ventral forebrain. These knockout mice showed (a) behavioral abnormalities similar to those described in psychiatric disorders, which were ameliorated by typical or atypical antipsychotics, (b) altered dopamine and serotonin levels in the brain, (c) decreases in spine density in neurons of the prefrontal cortex, (d) reductions in the protein levels of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor and post-synaptic protein-95 (PSD-95), (e) decreases in the EGF receptor, and in the calcium/calmodulin-dependent protein kinase II (CaMK II) signal cascade. These results suggest the alterations affecting HB-EGF signaling could comprise a contributing factor in psychiatric disorder.


Subject(s)
Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/physiology , Animals , Antipsychotic Agents/pharmacology , Behavior, Animal , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Disks Large Homolog 4 Protein , Dopamine/metabolism , ErbB Receptors/metabolism , Female , Heparin-binding EGF-like Growth Factor , Intracellular Signaling Peptides and Proteins/metabolism , Male , Membrane Proteins/metabolism , Mice , Mice, Knockout , Neurons/metabolism , Prosencephalon/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Serotonin/metabolism
9.
Biol Pharm Bull ; 32(9): 1576-83, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19721235

ABSTRACT

We investigated the involvement of glutamic acid in neural development by injecting phencyclidine (PCP) into neonatal ICR mice. Neonatal mice were injected with PCP at 10 mg/kg or saline on postnatal days 7, 9 and 11, and their behavioral, anatomical and neurochemical changes were analyzed in adulthood. PCP-treated mice exhibited an increase in PCP-induced hyperactivity and impairments of spatial working memory and social interaction behavior. The impairment of social interaction behavior was significantly reversed by administration of clozapine, D-cycloserine, flumazenil, or SHC50911, a gamma-aminobutyrate B (GABA(B)) receptor antagonist. A decrease in the number of parvalbumin-positive cells and spine density in the frontal cortex, nucleus accumbens and hippocampus were evident in the brains of PCP-treated mice. Measurement of brain monoamine and their metabolite contents in adulthood indicated brain area-dependent and neurotransmitter-specific changes in monoamine metabolism. These findings suggest that neonatal treatment with PCP in mice leads to enhanced sensitivity to PCP and impairment of spatial working memory and social interaction behaviors in adulthood, which may be associated with reduced spine density and GABAergic interneurons and changes in monoamine metabolism. Furthermore, pharmacologic experiments suggest the potential applicability of neonatally PCP-treated mice as a useful animal model for new antipsychotic drug screening.


Subject(s)
Aging/drug effects , Aging/metabolism , Behavior, Animal/drug effects , Brain Chemistry/drug effects , Brain/drug effects , Brain/pathology , Phencyclidine/toxicity , Aging/physiology , Animals , Animals, Newborn , Behavior, Animal/physiology , Biogenic Monoamines/metabolism , Brain Chemistry/physiology , Interpersonal Relations , Male , Memory/drug effects , Memory/physiology , Mice , Mice, Inbred ICR , Motor Activity/drug effects , Motor Activity/physiology , Schizophrenia/chemically induced , Schizophrenia/metabolism , Schizophrenia/pathology
10.
Brain Res ; 1208: 160-9, 2008 May 07.
Article in English | MEDLINE | ID: mdl-18381208

ABSTRACT

The responses of olfactory bulbectomized (OBX) rats to antidepressant treatment are similar to those of depressed patients since chronic administration of an antidepressant reverses OBX-induced behavioral and physiological changes. Previously, using several animal models, it was demonstrated that single treatment with delta-opioid receptor agonists produced an antidepressant-like effect. This study examined the antidepressant effects resulting from subchronic exposure for 8 days to the delta-opioid receptor agonist SNC80 in an OBX rat model of depression. The olfactory bulbs were removed by suction. The emotionality of rats was measured by scoring their responses to given stimuli, i.e., attack, startle, struggle, and fight responses. The OBX rats chronically treated with vehicle for 7 days at 14 days following surgery showed a significant increase in emotionality score and a decrease in the time spent and entries in the open arm of a plus-maze. In the case of OBX rats, these changes were dose- and time-dependently reversed by chronic SNC80 treatment (1-10 mg/kg, s.c.) for 7 days, as same as desipramine (10 mg/kg, i.p.). Moreover, the concentration of 5-HT and its metabolite 5-HIAA in the frontal cortex, hippocampus, and amygdala were decreased in OBX rats, and these changes were also normalized by SNC80 treatment, rather than desipramine treatment. In addition, SNC80 also significantly reversed the loss of TH-positive cells produced by OBX in the dorsal raphe. In conclusion, we demonstrated that subchronic SNC80 treatment could completely reverse OBX-induced behavioral abnormalities and defects in serotonergic function.


Subject(s)
Antidepressive Agents/pharmacology , Benzamides/pharmacology , Depression/drug therapy , Olfactory Bulb/physiopathology , Piperazines/pharmacology , Analysis of Variance , Animals , Behavior, Animal/drug effects , Brain/drug effects , Brain/metabolism , Brain/pathology , Depression/etiology , Depression/pathology , Desipramine/therapeutic use , Disease Models, Animal , Dose-Response Relationship, Drug , Male , Maze Learning/drug effects , Olfactory Bulb/injuries , Rats , Rats, Wistar , Serotonin/metabolism , Time Factors , Tryptophan Hydroxylase/metabolism
11.
Pathophysiol Haemost Thromb ; 36(5): 245-50, 2008.
Article in English | MEDLINE | ID: mdl-19996634

ABSTRACT

In this study, we examined the effects of alteplase, a recombinant tissue-type plasminogen activator (t-PA), in a simple and reproducible rat middle cerebral artery (MCA) occlusion model induced by photoillumination with 12 mg/kg of rose bengal. A clinically equivalent dose of alteplase (3 mg/kg), which was administered just after thrombotic occlusion of the MCA, significantly reopened the thrombotic MCA occlusion in 16 of 23 animals (69.6%) when compared with vehicle-treated animals (8 of 22 animals, 36.4%). In addition, alteplase significantly reduced cerebral damage and improved neurological deficits. Although it has been reported that t-PA possesses neurotoxicity, the present findings suggest that alteplase was effective in a rat acute stroke model due to reopening of thrombotic MCA occlusion. This new model is very useful for investigating the efficacy of thrombolytic agents in stroke research, providing a condition similar to the clinical setting.


Subject(s)
Infarction, Middle Cerebral Artery/drug therapy , Tissue Plasminogen Activator/pharmacology , Animals , Disease Models, Animal , Fibrinolytic Agents , Rats , Stroke/prevention & control , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome
13.
Masui ; 56(3): 324-5, 2007 Mar.
Article in Japanese | MEDLINE | ID: mdl-17366920

ABSTRACT

Pompe or glycogen storage disease type II is a genetic disorder affecting the cardiac and skeletal muscle. A 4-year-old boy with this disease was scheduled to undergo an orthopedic operation for clubbed foot. He had cardiomyopathy and skeletal muscle weakness; but his cardiac function was normalized by the long-term enzyme replacement therapy. General anesthesia was slowly induced with oxygen, nitrous oxide, and sevoflurane, and tracheal intubation was achieved without any muscle relaxants. In combination with a caudal blockade with 6 ml of 0.375% ropivacaine, general anesthesia was successfully maintained with oxygen, nitrous oxide, and sevoflurane. We did not use muscle relaxants to avoid prolonged respiratory depression. The perioperative course was uneventful and no complication was observed.


Subject(s)
Anesthesia, General , Glycogen Storage Disease Type II/surgery , Perioperative Care , Child, Preschool , Clubfoot/surgery , Humans , Intubation, Intratracheal , Male , Methyl Ethers , Neuromuscular Agents , Nitrous Oxide , Orthopedic Procedures , Oxygen , Prognosis , Respiratory Insufficiency/prevention & control , Sevoflurane
14.
Psychopharmacology (Berl) ; 191(4): 857-65, 2007 May.
Article in English | MEDLINE | ID: mdl-17318509

ABSTRACT

RATIONALE: It has been reported that many of the behavioral and serotonergic neuronal changes observed in olfactory bulbectomy (OBX) were improved by subchronic administration of a variety of antidepressants. OBJECTIVE: We examined the effects of subchronic treatment with milnacipran, a dual serotonin and noradrenaline reuptake inhibitors (SNRIs) and fluvoxamine, selective serotonin reuptake inhibitors (SSRI) in the OBX-induced hyperemotional behaviors and tryptophan hydroxylase (TPH), rate-limiting enzyme of 5-HT. MATERIALS AND METHODS: The olfactory bulbs were removed by suction. Drugs were administered p.o. once daily for 8 days beginning 14 days post-surgery. The hyperemotionality behaviors of OBX rats were measured by rating scale and in the elevated plus-maze test. RESULTS: OBX rats, after milnacipran or fluvoxamine treatment, showed significant decrease in the score of hyperemotional responses on 7th day as compared with vehicle-treated OBX rats. In addition, milnacipran and fluvoxamine in OBX rats respectively produced a significant increase in the percentage of time spent in and number of entries into open arms in the elevated plus maze test. Furthermore, when 5-HTnergic neuronal function was examined using antibodies against tryptophan hydroxylase (TPH) following the behavioral tests, fluvoxamine significantly reversed the loss of TPH-positive cells produced by OBX in the dorsal raphe. CONCLUSION: We demonstrated that chronic treatment with milnacipran or fluvoxamine was effective to improve both the hyperemotional behavior and the loss of TPH-positive cells seen in OBX rats.


Subject(s)
Adrenergic Uptake Inhibitors/pharmacology , Behavior, Animal/drug effects , Cyclopropanes/pharmacology , Emotions/drug effects , Fluvoxamine/pharmacology , Raphe Nuclei/drug effects , Selective Serotonin Reuptake Inhibitors/pharmacology , Tryptophan Hydroxylase/metabolism , Animals , Dose-Response Relationship, Drug , Male , Milnacipran , Motor Activity/drug effects , Neurons/drug effects , Neurons/enzymology , Olfactory Bulb/surgery , Raphe Nuclei/cytology , Raphe Nuclei/enzymology , Rats , Rats, Wistar , Serotonin/metabolism , Time Factors
16.
Masui ; 54(6): 662-4, 2005 Jun.
Article in Japanese | MEDLINE | ID: mdl-15966386

ABSTRACT

We report a case of a 35-year-old woman with myotonic dystrophy and severe obesity of BMI 43.3 who showed persistent apnea at emergence after ovarian resection. The patient received an iv induction with minimum dose of propofol and vecuronium 3 mg. Anesthesia was maintained with propofol, 50% nitrous oxide and 50% oxygen mixture and epidural anesthesia. Additional vecuronium 0.5 mg was administered twice. Surgery was performed uneventfully within 130 minutes and iv propofol was discontinued. The patient awoke promptly after termination of nitrous oxide but no spontaneous breathing appeared with end-tidal CO2 of 60 mmHg. Because she could obey the order to breathe, the endotracheal tube was removed 40 minutes after discontinuation of propofol. Spontaneous breathing at the rate of 17 x min(-1) started soon after extubation. We assume that this apnea was caused by breath holding. Whether this breath holding is specific to myotonic dystrophy or not, anesthesia for patients with this disease requires careful attention for perioperative respiratory management.


Subject(s)
Anesthesia, General , Apnea/etiology , Myotonic Dystrophy/complications , Obesity/complications , Adult , Anesthesia Recovery Period , Anesthesia, Epidural , Anesthesia, General/methods , Female , Humans , Ovariectomy
17.
Article in Japanese | MEDLINE | ID: mdl-12762219

ABSTRACT

With the recent appearance of SSRI and SNRI, medication options with respect to depression have broadened. However, patients displaying clear improvement with existing antidepressants still do not exceed about 60 percent of total patients. New types of therapeutic agent development are currently required. Conditions for the determination of new antidepressants are: 1) instantaneous medications displaying a high level of antidepressant action in the early stages of treatment and 2) medications displaying efficacy with respect to patients that are therapy-resistant. However, drug discovery using new animal models is critical as part of drug development of these types of antidepressants in addition to models used in the past such as the forced swim test. We adopted two animal models (olfactory bulbectomy model and conditioned fear stress (CFS) model) developed for pharmacological evaluation of antidepressants. It has been well known that olfactory bulbectomied rats display extreme emotional response (aggressiveness and anxiety). However the improvement of this response occurs following chronic but not acute antidepressant treatment. Thus, we used this model to evaluate the period of the manifestation of antidepressant action. Mice exhibited a marked suppression of motility when they were returned to the same environment in which they had previously received an electric foot shock. Thus, it is suggested that the CFS stress model may be a useful model for therapy-resistant depression due to the fact that motor suppression is not readily attenuated by antidepressant treatment. In this report, we provide an overview of the approaches in the discovery of new antidepressants using these affective disorder models.


Subject(s)
Antidepressive Agents/therapeutic use , Conditioning, Psychological , Disease Models, Animal , Drug Design , Mood Disorders/drug therapy , Olfactory Bulb/surgery , Animals , Humans , Male , Mice , Mood Disorders/etiology , Rats , Rats, Wistar
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