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

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*

To investigate the changes in the expression of basic fibroblast growth factor (bFGF) and transforming growth factor beta 2 (TGFbeta2) in glomus cell grafts of carotid body in the rat model of 6-hydroxydopamine-induced Parkinson disease, immunohistochemical staining of bFGF and TGFbeta2 in the sections of striate body was done on the 2nd, 4th and 12th week after transplantation. The results showed that on the 2nd week after transplantation, bFGF and TGFbeta2 were not detectable in the glumous cell grafts. On the 4th week after graft, bFGF and TGFbeta2 immunoreactivity was increased within the grafts and at the graft-host interface but was restricted only to astrocytes. In the striatum surrounding the graft, bFGF was expressed persistently, while TGFbeta2 showed transient expression. It was suggested that the transient expression of TGFbeta2 was likely due more to the trauma imposed by the graft procedure than to an intrinsic. The deficiency in astrocytic bFGF early after graft may be responsible for the poor survival of grafted glomus cells of carotid body.
Animals ; Carotid Body ; cytology ; transplantation ; Female ; Fibroblast Growth Factor 2 ; biosynthesis ; genetics ; Hydroxydopamines ; Parkinson Disease ; etiology ; metabolism ; surgery ; Rats ; Transforming Growth Factor beta ; biosynthesis ; genetics ; Transforming Growth Factor beta2 ; Transplantation, Homologous

No abstract available.
Models, Animal* ; Oxidopamine* ; Parkinsonian Disorders*

No abstract available.
Animals ; Neurons* ; Oxidopamine* ; Rats* ; Substantia Nigra*

OBJECTIVE: In this experimental study, authors evaluated the effect of repeated graft of the fetal midbrain cells on rat model of hemiparkinsonism. MATERIALS AND METHODS: Following injection of the 6-hydroxydopamine into striatum, we examined the behavior (turning response to amphetamine and apomorphine) at 2, 4 and 8 weeks. Their turning behavior persisted until 8 weeks after lesion making. Only those with turning behavior of more than average 6.2turns/minute by amphetamine test were selected for transplantation. Three different methods of transplantation were assigned into three groups and compared with each other to evaluate their efficiencies in improving behavioral responses. In first method, the volume of the transplanted cells were equivalent to that of one fetal midbrain. The volume of the transplanted cells were twice as much as that of one fetal midbrain in a group with second method. The last group consisted of repeated transplantation. Here, we transplanted the same amount of fetal midbrain cells as the in group 2 with two divided doses in one month interval. RESULTS: The second and third group improved from amphetamine test significantly(p<0.05), whereas first group failed to show any significant improvement from same test. The results from second and third group were not significantly different from each other. CONCLUSION: This results suggest that transplantation of two volumes of the fetal midbrain is needed to improve the turning behavior of this model of parkinsonism. This volume can be tansplanted at once or it may be transplanted in two divided volumes with time interval, with similar effect.
Amphetamine ; Animals ; Mesencephalon ; Models, Animal* ; Oxidopamine* ; Parkinsonian Disorders ; Rats* ; Transplants*

Unilateral obstruction or injury to the vas deferens can result in significant injury to the contralateral testicle. Although various pathways have been proposed, the mechanism of contralateral testicular deterioration remains controversial. The present animal study was performed to evaluate the effects of unilateral vasectomy on ipsilateral and contralateral testicular histology and fertility in rats that were chemically sympathectomized neonatally. The study comprised 40 male albino rats: 20 received a placebo and the other 20 underwent chemical sympathectomy neonatally. When 60 days old, each group of 20 rats was divided into two groups that underwent either a sham operation or an operation to create unilateral left vasectomy. Eight weeks after surgery, each male rat was housed with two known fertile female rats for 25 days, and then their testes were harvested. Mean seminiferous tubular diameters (MSTD) and mean testicular biopsy scores (MTBS) were determined for each testis. Although MSTD and MTBS were not significantly different between groups, chemical sympathectomy prevented the decrease in total fertility rates of the rats with unilateral left vasectomy in our study. Prevention of this decrease by chemical sympathectomy suggests that the sympathetic nervous system may play a role in the testicular degeneration associated with vasectomy.
Animals ; Female ; Fertility/*drug effects ; Male ; Oxidopamine/toxicity ; Rats ; *Sympathectomy, Chemical ; Testis/drug effects/*pathology ; *Vasectomy

Recently the reports of the autologous grafting of adrenal medullary tissue into the brain of parkinsonian patient have given the wide attention to the neurosurgeons as well as other clinicians, because the current therapeutic modalities are either imperfect or palliative. Although neural grafting of adrenal medullary tissue of fetal brain which can supply the dopamine seems to be a ideal form of treatment theoretically, many problems must be overcome for this approach to be a routine procedure. Authors made the rat parkinsonian model by destroying the substantia nigra and nigrostriatal fiber selectively with 6-OHDA. And abnormal behaviors and growth patterns were observed and studied using rotometry, T-maze and metabolic cage. With the results, some parameters which would be useful in further experiments could be established.
Animals ; Brain ; Dopamine ; Humans ; Oxidopamine ; Parkinson Disease ; Rats* ; Substantia Nigra ; Transplants

Fetal dopaminergic or nondopaminergic cortical tissues were implanted directly into the denervated striatum of partial lesioned rat parkinsonian models. After transplantation, at rats were behaviourally tested with apomorphine and sacrificed for tyrosine hydroxylase immunohistochemical stain. The results of this study are summarized as follows : 1) Of 45 rats partially lesioned with 6-hydroxydopamine, 17 rats(37.8%) met a criteria(a minimum of 4 times/min to apomorphine-induced rotation test) of the rat parkinsonian model. 2) Eight weeks after transplantation of the fetal dopaminergic tissues into the striatum of the rat parkinsonian model, transplanted dopaminergic cells were found to be alive. Also reinnervated dopaminergic fibers were found in the previously denervated striatum. And the behavioural study suggested that the transplantation of the fetal dopaminergic neurons had influenced on the apomorphine-induced rotation. 3) Eight weeks after transplantation of the fetal nondopaminergic tissues into the striatum of the rat parkinsonian model, dopaminergic cells were not found in the previously denervated striatum. However, reinnervation of the dopaminergic fibers were found in the preciously denervated striatum. However, reinnervation of the dopaminergic fibers were found in the previously denervated striatum as well as the reduction of the apomorphine-induced rotation compared to the pregraft state. The major finding of this study support a trophic hypothesis for the mechanism of recovery in response to fetal dopaminergic or nondopaminergic tissue. The author conclude that fetal nondopaminergic tissue also had some beneficial effect in reducing apomorphine-induced rotational asymmetry probably by promoting recovery or sprouting of remaining dopaminergic fibers at the previously denervated striatum of the rat parkinsonian model.
Animals ; Apomorphine ; Dopaminergic Neurons ; Oxidopamine ; Rats* ; Tissue Transplantation* ; Transplantation ; Transplants* ; Tyrosine 3-Monooxygenase

BACKGROUND: Apomorphine-induced rotational behavior of unilateral 6-hydroxydopamine (OHDA) lesioned rat is widely used to develop anti-Parkinsonian treatments including drugs, neuroprotective therapy, and neural graft. Time course of changes in rotational behavior after lesioning, however, has not been fully elucidated. The aim of this study was to observe the chronological changes in the rotational response and to find the optimal period when this model is used for investigation of various therapies. METHODS: 6-OHDA was stereotaxically delivered to the unilateral substantia nigra in 13 rats. Rotational responses to apomorphine administrations were counted in the rotomotor on 2, 4, 8, 12, and 14 weeks after lesioning. RESULTS: The total turns for two hours increased continuously up to eight weeks, and then plateaued. CONCLUSIONS: Apomorphine-induced rotations increase until eight weeks after 6-OHDA lesioning. Therefore, this Parkinsonian model should be used at least eight weeks after lesioning. Even though priming was not excluded as an explanation in the experiment, we reason that progressive degeneration of dopaminergic neurons may explain the chronological changes in rotational behavior.
Animals ; Apomorphine* ; Dopaminergic Neurons ; Neuroprotective Agents ; Oxidopamine* ; Rats* ; Substantia Nigra ; Transplants