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PubMed1984

Time-dependent rotational rates of excited fluorophores. A linkage between fluorescence depolarization and solvent relaxation.

It is generally assumed that the rotational diffusion coefficients of fluorophores are independent of time subsequent to excitation, and that the rotational diffusion coefficients of the ground and the excited states are the same. We now describe a linkage between the extent of solvent relaxation and the rate of fluorescence depolarization. Specifically, if a fluorophore displays time-dependent solvent relaxation it may also show a time-dependent decrease in its rotational rate. A decreased rate of rotation could result from the increased interaction with polar solvent molecules which occurs as a result of solvent relaxation. The decays of anisotropy predicted from our model closely mimic those often observed for fluorophores which are bound to macromolecules. For example, the decays are more complex than a single exponential, and the time-resolved anisotropy can display a limiting value which does not decay to zero. The effect of solvent relaxation upon the rates of rotational diffusion is expected to be most dramatic for solvent-sensitive fluorophores in a viscous environment. These conditions are frequently encountered for fluorophore-macromolecule complexes. Consideration of the linkage between solvent relaxation and rotational diffusion leads to two unusual predictions. First even spherical fluorophores in an isotropic environment could display multi- or nonexponential decays of fluorescence anisotropy. Secondly, for the special case in which the fluorophore dipole moment decreases upon excitation, the theory predicts that the anisotropy decay rate may increase with time subsequent to pulsed excitation. The predictions of this theory are consistent with published data on the effects of red-edge excitation upon the apparent rotational rates of fluorophores in polar solvents.

Journal Article↗
PubMed2004

Effects of glenohumeral rotations and translations on supraspinatus tendon morphology.

OBJECTIVE: The purpose of this study was to evaluate the effects of glenohumeral rotations and humeral head translations on supraspinatus tendon morphology. DESIGN: A convenience sample of cadaver shoulders was used to measure supraspinatus tendon shape and dimensions from MRI images. BACKGROUND: Epidemiological evidence has indicated that shoulder elevation and external rotation may be risk factors for rotator cuff tendon pathology, but little is known about how these postures affect tendon morphology. METHODS: Measurements of supraspinatus tendon morphology were made from three-dimensional reconstructions based on T2-weighted fast spin-echo magnetic resonance images. Seven cadaver arms were imaged at neutral, 45 degrees external and 45 degrees internal rotations at 0 degrees, 30 degrees, and 60 degrees of glenohumeral abduction. Measurements of the anterior, middle, and posterior portions of the tendon were made using ANALYZE software. RESULTS: The supraspinatus tendon was twisted at the muscle-tendon junction of the middle and posterior portions in 45 degrees external and 45 degrees internal axial rotations of the humerus, especially over 30 degrees of abduction. Abduction over 30 degrees shortened the entire supraspinatus tendon. External and internal rotation motions elongated the anterior and posterior portions, respectively. CONCLUSIONS: Arm posture affects morphology of the supraspinatus tendon. RELEVANCE: The results support the epidemiologic evidence linking external rotation and abduction to supraspinatus tendon disorders.

Aged↗
PubMed2005

The detection of non-RoTat 1.2 Trypanosoma evansi.

The majority of Trypanosoma evansi can be detected using diagnostic tests based on the variant surface glycoprotein (VSG) of Trypanosoma evansi Rode Trypanozoon antigen type (RoTat) 1.2. Exceptions are a number of T. evansi isolated in Kenya. To characterize T. evansi that are undetected by RoTat 1.2, we cloned and sequenced the VSG cDNA from T. evansi JN 2118Hu, an isolate devoid of the RoTat 1.2 VSG gene. A 273 bp DNA segment of the VSG gene was targeted in PCR amplification for the detection of non-RoTat 1.2 T. evansi. Genomic DNA samples from different trypanosomes were tested including 32 T. evansi, 10 Trypanosoma brucei, three Trypanosoma congolense, and one Trypanosoma vivax. Comparison was by PCR amplification of a 488 bp fragment of RoTat1.2 VSG gene. Results showed that the expected 273 bp amplification product was present in all five non-RoTat 1.2 T. evansi tested and was absent in all 27 RoTat 1.2-positive T. evansi tested. It was also absent in all other trypanosomes tested. The PCR test developed in this study is specific for non-RoTat 1.2 T. evansi.

Amino Acid Sequence↗
PubMed2006

Magnitude and clinical relevance of translational and rotational patient setup errors: a cone-beam CT study.

PURPOSE: To establish volume imaging using an on-board cone-beam CT (CB-CT) scanner for evaluation of three-dimensional patient setup errors. METHODS AND MATERIALS: The data from 24 patients were included in this study, and the setup errors using 209 CB-CT studies and 148 electronic portal images were analyzed and compared. The effect of rotational errors alone, translational errors alone, and combined rotational and translational errors on target coverage and sparing of organs at risk was investigated. RESULTS: Translational setup errors using the CB-CT scanner and an electronic portal imaging device differed <1 mm in 70.7% and <2 mm in 93.2% of the measurements. Rotational errors >2 degrees were recorded in 3.7% of pelvic tumors, 26.4% of thoracic tumors, and 12.4% of head-and-neck tumors; the corresponding maximal rotational errors were 5 degrees , 8 degrees , and 6 degrees . No correlation between the magnitude of translational and rotational setup errors was observed. For patients with elongated target volumes and sharp dose gradients to adjacent organs at risk, both translational and rotational errors resulted in considerably decreased target coverage and highly increased doses to the organs at risk compared with the initial treatment plan. CONCLUSIONS: The CB-CT scanner has been successfully established for the evaluation of patient setup errors, and its feasibility in day-to-day clinical practice has been demonstrated. Our results have indicated that rotational errors are of clinical significance for selected patients receiving high-precision radiotherapy.

Head and Neck Neoplasms↗
PubMed2004

Does egocentric mental rotation elicit sex differences?

Mental rotation tests traditionally show a male performance advantage. Some neuroimaging studies have reported sex-specific cortical activation patterns during mental rotation. However, these experiments used abstract stimuli and some studies did not systematically exclude performance as a confounding variable. The mental rotation of hands and hand-related objects, compared to abstract objects, is known to evoke an egocentric motor strategy. In this study, we used fMRI to explore potential gender-specific cortical activation patterns for the mental rotation of hands and tools in a sample with an adequate and equal performance for men and women. We found a common neural substrate for men and women comprising superior parietal lobe, dorsolateral premotor cortex, and extrastriate occipital areas, compatible with an egocentric motor strategy for the mental rotation of hands and tools. Sex differences were modest and limited to the mental rotation of hands. Women recruited more left ventral premotor cortex, which could imply that women rely more on imitation or use more perceptual comparisons. Men, on the other hand, drafted more the lingual gyrus, possibly referring to more extensive semantic or early visual processing. We conclude that men and women use a very similar motor strategy during egocentric mental rotation with a potential gender-specific accent.

Adult↗
PubMed2004

Can rotation osteotomy remain effective for more than ten years?

Trochanteric rotation osteotomies displace the necrotic zone of the femoral head outside the major acetabular weight-bearing zone and rotate the head anteriorly or posteriorly. Nineteen consecutive patients were selected for rotation osteotomy based on age,absence of progressive disease, and preoperative imaging studies predicting that rotation osteotomy would move the entire necrotic zone away from the acetabular roof. Factors associated with failure were head flattening and necrosis deeper than one third of the femoral head diameter. Among patient subsets with identical disease stages, outcomes seemed better after posterior rotation than after anterior rotation. Rotation osteotomies,fixed by a nail plate, can be recommended in a few selected patients with shallow necrosis involving less than one third of the femoral head diameter and without osteoarthritis or head flattening. Under these conditions, good outcomes may be achieved for 10 years or longer.

Adolescent↗
PubMed2001

Eccentric head positions bias random generation of leftward and rightward handle-bar rotations.

We explored the effects of eccentric head positions on rapid rotations of a handle-bar in a modified randomization task. Subjects had to generate a random sequence of leftward and rightward handle-bar rotations; each pre-selected rotation was produced in response to a visual signal as rapidly as possible. Eccentric head positions induced a bias in that handle-bar rotations in the direction of the eccentric head position were chosen more frequently than handle-bar rotations in the opposite direction. This is consistent with previous evidence on a spatial coupling. In contrast to response selection, response initiation was not affected by eccentric head positions. The kinematic characteristics, however, differed: rotations in the direction of the eccentric head position were of larger amplitude and longer duration than rotations in the opposite direction. This difference may have been secondary to a difference in the start positions of the handle-bar, which were shifted in the direction opposite to the eccentric head position.

Adult↗
PubMed2003

Comparison of rotational atherectomy with conventional balloon angioplasty in the prevention of restenosis of small coronary arteries: results of the Dilatation vs Ablation Revascularization Trial Targeting Restenosis (DART).

BACKGROUND: The optimum treatment of obstructive coronary disease in small (<3.0 mm diameter) arteries remains unknown. Rotational atherectomy is an approved treatment that might reduce the vascular injury during percutaneous coronary intervention compared with angioplasty. We report on a multicenter, randomized, blinded end point trial comparing rotational atherectomy with balloon angioplasty in the prevention of restenosis of obstructed small coronary arteries. METHODS: A total of 446 patients with myocardial ischemia associated with an angiographic stenosis in a native coronary artery 2 to 3 mm in diameter and < or =20 mm in length without severe calcification were randomly assigned to receive rotational atherectomy (n = 227) or balloon angioplasty (n = 219). The primary end point was target vessel failure at 12 months (defined as the composite of death, Q-wave myocardial infarction, and clinically driven repeat revascularization of the target vessel). RESULTS: The mean reference vessel diameter was 2.46 +/- 0.40 mm, the mean lesion length was 9.97 +/- 5.59 mm, and the prevalence of diabetes mellitus was 32%. Acute procedural success (91.6% for rotational atherectomy, 94.1% for balloon angioplasty, P =.36) and target vessel failure at 12 months were not significantly different (30.5% vs 31.2%, P =.98). At 8 months, there were no significant differences in minimum lumen diameter (1.28 +/- 0.63 mm vs 1.19 +/- 0.54 mm, P =.26), percent diameter stenosis (28% +/- 12% vs 29% +/- 15%, P =.59), binary restenosis rate (50.5% vs 50.5%, P = 1.0), or late loss index (0.57 vs 0.62, P =.7). No Q-wave myocardial infarctions occurred in either arm of the study, and non-Q-wave myocardial infarctions (defined as creatine kinase level >2 times normal with an elevated creatine kinase-myocardial band isoenzyme level) occurred in 2.2% and 1.4% of the patients in the rotational atherectomy and balloon angioplasty groups, respectively (P =.72). CONCLUSION: Rotational atherectomy was found to be safe in the treatment of obstructed small arteries, but lower rates of target vessel failure were not achieved compared with balloon angioplasty. Because the acute gain and loss index ratios of the 2 treatments were similar, there was no evident beneficial antirestenosis mechanism seen for rotational atherectomy.

Angioplasty, Balloon, Coronary↗
PubMed1998

Quantitative angiography of coronary artery dimensions 24 hours after rotational atherectomy.

Rotational atherectomy results in platelet activation and heat generation, which may impact artery size immediately after treatment. In addition, arteries treated with balloon angioplasty may exhibit recoil within 24 hours. In this study, arteries treated with rotational atherectomy, with and without adjunctive balloon angioplasty, were analyzed by quantitative coronary angiography to determine the effect of rotational atherectomy on the dynamic behavior of the arterial wall within 24 hours after the procedure. Quantitative coronary angiography was performed at a core laboratory. Coronary angiogram acquisitions were preceded by intracoronary nitroglycerin injections and were repeated using identical angles of projection. Proximal and distal reference vessel diameters were 2.55 +/- 0.60 and 2.28 +/- 0.51 mm, respectively, and did not change from pre- to postprocedure. Both were larger the following day increasing to 2.72 +/- 0.65 and 2.52 +/- 0.52 mm, respectively, (p <0.001). Minimum luminal diameter (MLD) increased from 0.70 +/- 0.28 mm before to 1.49 +/- 0.34 mm after the procedure and to 1.72 +/- 0.37 mm at 24-hour follow-up (p <0.001). Subset analysis of patients treated with rotational atherectomy alone or rotational atherectomy with adjunctive balloon angioplasty revealed that the increase in luminal diameters occurred in both subsets. Patients treated with adjunctive angioplasty had a smaller initial MLD, a larger postprocedure MLD, and no difference in MLD at 24-hour follow-up compared with stand-alone rotational atherectomy. Subset analysis of 100 patients who had 6-month follow-up angiography revealed that both a calculated acute gain and chronic late loss, based on a 24-hour film, differed significantly from values using a film acquired immediately after the procedure. However, the slope of the linear regression between acute gain and chronic late loss did not differ. Coronary arteries treated with rotational atherectomy with or without adjunctive balloon angioplasty increase significantly in size during the first 24 hours after the procedure. This phenomenon has implications for the calculation of absolute gain and chronic late loss, but not for the linear relation between the 2 quantitative outcomes.

Aged↗
PubMed1999

Rotational versus nonrotational forceps: maternal and neonatal outcomes.

OBJECTIVE: Our purpose was to evaluate maternal and neonatal morbidity associated with rotations performed with Leff forceps in comparison with nonrotational forceps deliveries. STUDY DESIGN: A review of 267 rotational and nonrotational forceps deliveries from August 1996 through February 1998 was performed. Multiple maternal and neonatal outcome measures were compared and results were analyzed by chi(2) with the Fisher exact test and the Student t test. RESULTS: One hundred sixty-three traditional low-forceps or outlet forceps deliveries were compared with 104 rotational forceps deliveries performed with Leff forceps. There were no significant differences between the 2 groups in maternal age, gestational age, gravidity, parity, total labor duration, birth weight, and Apgar scores. There were significantly lower rates of episiotomy, third- and fourth-degree lacerations, and sulcus lacerations in the rotation group, and the second stage of labor was also shorter. The neonatal intensive care unit admission rate was higher in the rotation group; however, none of the admissions were directly related to the mode of delivery. CONCLUSION: Rotational deliveries performed with Leff forceps are associated with less maternal morbidity and shorter second stage of labor than are deliveries performed with traditional forceps. Leff forceps are a safe option for rotation of the persistent occipitoposterior fetal position.

Adult↗
PubMed1978

Detection of hindered rotations of 1,6-diphenyl-1,3,5-hexatriene in lipid bilayers by differential polarized phase fluorometry.

Differential polarized phase fluorometry has been used to investigate the depolarizing motions of 1,6-diphenyl-1,3,5-hexatriene (DPH) in the isotropic solvent propylene glycol and in lipid bilayers of dimyristoyl-L-alpha-phosphatidylcholine (DMPC), dipalmitoyl-L-alpha-phosphatidylcholine (DPPC), and other phosphatidylcholines. Differential phase fluorometry is the measurement of differences in the phase angles between the parallel and perpendicular components of the fluorescence emission of a sample excited with sinusoidally modulated light. The maximum value of the tangent of the phase angle (tan Delta(max)) is known to be a function of the isotropy of the depolarizing motions. For DPH in propylene glycol the maximum tangent is observed at 18 degrees C, and this tangent value corresponds precisely with the value expected for an isotropic rotator. Additionally, the rotational rates determined by steady-state polarization measurements are in precise agreement with the differential phase measurements. These results indicate that differential phase fluorometry provides a reliable measure of the probe's rotational rate under conditions where these rotations are isotropic and unhindered.Rotational rates of DPH obtained from steady-state polarization and differential phase measurements do not agree when this probe is placed in lipid bilayers. The temperature profile of the tan Delta measurements of DPH in DMPC and DPPC bilayers is characterized by a rapid increase of tan Delta at the transition temperature (T(c)), followed by a gradual decline in tan Delta at temperatures above T(c). The observed tanDelta(max) values are only 62 and 43% of the theoretical maximum. This defect in tanDelta(max) is too large to be explained by any degree of rotational anisotropy. However, these defects are explicable by a new theory that describes the tan Delta values under conditions where the probe's rotational motions are restricted to a limiting anisotropy value, r(infinity). Theoretical calculations using this new theory indicate that the temperature dependence of the depolarizing motions of DPH in these saturated bilayers could be explained by a rapid increase in its rotational rate (R) at the transition temperature, coupled with a simultaneous decrease in r(infinity) at this same temperature. The sensitivity of the tan Delta values to both R and r(infinity) indicates that differential phase fluorometry will provide a method to describe more completely the depolarizing motion of probes in lipid bilayers.

Membranes, Artificial↗
PubMed1982

Dynamic depolarization of interacting fluorophores. Effect of internal rotation and energy transfer.

Effects of internal rotation on the fluorescence decay functions and time-dependent anisotropies of fluorophores bound to a spherical macromolecule are theoretically investigated in the presence of the intramolecular energy transfer interaction by solving relevant rotational diffusion equations. The model system examined is one in which the energy donor is internally rotating around an axis fixed at the macromolecule and the acceptor is fixed at a definite position in the macromolecule. The effect of internal rotation in the system is described by Hill's functions with two cosine terms. The fluorescence decay function and anisotropy decay are functions of the ratio of energy-transfer probability averaged over the internal rotation angle to the rotary diffusion co-efficient. When the internal rotation is much faster than energy transfer, the decay function of the donor is predicted to be a single exponential, and the anisotropy decay is essentially described by the expression derived by Gotlieb and Wahl (1963. J. Chim. Phys. 60:849-856). However, deviation from it becomes pronounced as the rotation becomes slower. Methods of numerical analysis are presented for decay function and anisotropy decay, as well as relative quantum yield and polarization anisotropy under steady-state excitation, and examined for a simplified system under the variation of the diffusion coefficient.

Energy Transfer↗
PubMed2006

Differential effects of transcranial magnetic stimulation of left and right posterior parietal cortex on mental rotation tasks.

A recently published study used the interference strategy of transcranial magnetic stimulation (TMS) to demonstrate the role of the right posterior parietal cortex (PPC) in the mental rotation of alphanumeric stimuli. We used similar stimulation parameters over the same left and right PPC regions, and examined the ability to rotate more complex 3D Shepard and Metzler (1971) images. There was reduced accuracy of performance with both right and left PPC stimulation for different angles of rotation of the visual stimuli. Right PPC stimulation led to reduced accuracy to rotate stimuli by 1200, whereas left PPC stimulation affected 180 degrees C rotation. We hypothesise that the two hemispheres make different contributions to the processing underlying visuospatial mental imagery: the right PPC is important for spatial rotations through smaller angles; the left hemisphere has a unique role when the stimuli to be compared are rotated through 180 degrees C, a task that engages verbal strategies due to the well-documented special nature of enantiomorphs.

Adult↗
PubMed2005

[Displacement of the instantaneous center of rotation of the humeral head during abduction: implication for scapulohumeral muscular function].

PURPOSE OF THE STUDY: To date, studies of glenohumeral stress forces have been based on the notion of a unique center of rotation situated at the geometric center of the humeral head. Early work, e.g. Fisher et al in 1977, suggested that the instantaneous center of rotation can migrate during abduction producing muscle vectors with variable moments and consequently variable stress forces. We conducted a kinematic analysis of the shoulder forces during continuous movement. MATERIAL AND METHODS: An imaging device commonly used for angiography enabled acquisition of one image per second during a continuous movement of abduction. Images were obtained for twenty healthy shoulders in ten subjects. RESULTS: The instantaneous center of rotation was not situated at the geometric center of the humeral head. Although interindividual variability was significant, the preferential positions of the instantaneous center of rotation implied a constant reproducible succession of gliding, rolling, and translation in variable proportions during the abduction movement. When the same movement was performed with a 3500g load held in the hand, the ICR migrated towards the upper part of the humeral head implying a predominance of the rolling motion over the gliding and translation motions. Between 40 degrees and 60 degrees glenohumeral abduction, the instantaneous center of rotation exhibited a metaphyseal displacement producing a longer lever arm for the supaspinatus and an abduction function for the infraspinatus and the subscapularis, unrecognized to date. After 60 degrees, medialization of the instantaneous center of rotation lengthened the lever arm of the deltoid. DISCUSSION: A valid analysis of the glenohumeral stress forces must take into consideration the localization of the instantaneous center of rotation. In the clinical setting, our findings demonstrate that the infraspinatus and the subscapularis play an important role which must be considered both in surgery and in rehabilitation.

Adult↗
PubMed1999

Optimisation of antihypertensive treatment by crossover rotation of four major classes.

BACKGROUND: Most comparisons of antihypertensive drugs are undertaken in parallel groups. We undertook a crossover rotation of the four main classes of antihypertensive drugs, in untreated young hypertensive patients, to assess the response rate with monotherapy achieved by a systematic rotation. METHODS: 56 patients, mean blood pressure 161/98 mm Hg, entered the rotation, of whom 36 received all four monthly cycles of treatment with an angiotensin-converting-enzyme (ACE) inhibitor (A), beta-blocker (B), calcium-channel blocker (C), and diuretic (D). Each patient's best drug was then repeated to assess repeatability. Two measures of individual variability in response were used. First, the value of rotation was measured by the increased proportion of patients reaching target blood pressure on their best drug versus their first drug. Second, we assessed whether the responses to each drug were correlated with each other. FINDINGS: Significant variability in response was found. 20 of the 41 patients reaching target blood pressure (< or =140/90 mm Hg) failed to achieve this target on their first drug. Rotation increased from 22/56 (39%) to 41/56 (73%) the success of monotherapy (p=0.0001); in half the patients, blood-pressure on the best treatment was 135/85 mm Hg or less. There were significant correlations between the blood pressure responses to A and B (r=0.5, p<0.01), and C and D (r=0.6, p<0.001), but not between the other four pairings of treatments. The responses to the AB pair were, on average, at least 50% higher than those to the CD pair; this difference was highly significant by multivariate repeated-measures ANOVA. INTERPRETATION: There is a marked variability in hypertensive patients' response to different antihypertensive drugs. The basis may be underlying variability in types of essential hypertension. Optimisation of treatment requires systematic rotation through several therapies; however, an "AB/CD" rule is proposed in which one of each of the two pairs of treatments is initially selected to abbreviate the rotation in routine practice.

Adrenergic beta-Antagonists↗
PubMed1998

Adaptation in a rotating artificial gravity environment.

The centripetal force generated by a rotating space vehicle is a potential source of artificial gravity. Minimizing the cost of such a vehicle dictates using the smallest radius and highest rotation rate possible, but head movements made at high rotation rates generate disorienting, nauseogenic cross-coupled semicircular canal stimulation. Early studies suggested 3 or 4 rpm as the highest rate at which humans could adapt to this vestibular stimulus. These studies neglected the concomitant Coriolis force actions on the head/neck system. We assessed non-vestibular Coriolis effects by measuring arm and leg movements made in the center of a rotating room turning at 10 rpm and found that movement endpoints and trajectories are initially deviated; however, subjects readily adapt with 10-20 additional movements, even without seeing their errors. Equilibrium point theories of motor control errantly predict that Coriolis forces will not cause movement endpoint errors so that subjects will not have to adapt their reaching movements during rotation. Adaptation of movement trajectory acquired during Coriolis force perturbations of one arm transfers to the unexposed arm but there is no intermanual transfer of endpoint adaptation indicating that neuromotor representations of movement endpoint and trajectory are separable and can adapt independently, also contradictory to equilibrium point theories. Touching a surface at the end of reaching movements is required for complete endpoint adaptation in darkness but trajectory adapts completely with or without terminal contact. We have also made the first kinematic measurements of unconstrained head movements during rotation, these movements show rapid adaptation to Coriolis force perturbations. Our results point to methods for achieving full compensation for rotation up to 10 rpm.

Adaptation, Physiological↗
PubMed1998

Opposite rotation induced by dopamine agonists in rats with unilateral lesions of the globus pallidus or substantia nigra.

Normal rats with a unilateral ibotenic acid lesion of substantia nigra pars reticulata (SNR, n = 12) or globus pallidus (GP, n = 12) were challenged systemically with the mixed dopaminergic agonist apomorphine (0.5 and 1.5 mg/kg) and the indirect acting d-amphetamine (1.5 mg/kg). The low dose of apomorphine produced a weak contralateral rotation only in the SNR-lesioned group, which showed an intense ipsilateral rotation following the administration of the higher dose. GP-lesioned rats also showed ipsilateral rotation after the high dose of apomorphine. d-Amphetamine produced ipsilateral rotation in GP-lesioned rats, contrasting with a vigorous contralateral rotation in SNR-lesioned rats. The unexpected opposite rotation after apomorphine and d-amphetamine, observed only in SNR-lesioned animals, indicates that the role of SNR in basal ganglia functions is less clear and more complex than what is expected from our current model of basal ganglia circuitry and functions. On the other hand, the GP lesion resulted in a consistent and predictable ipsilateral rotation after both apomorphine and d-amphetamine, indicating a more determinant effect on the output of the basal ganglia than heretofore believed. Our results may contribute to the recently expressed views challenging the established model of basal ganglia organisation.

Animals↗
PubMed1998

The role of nigrostriatal dopamine in metabotropic glutamate agonist-induced rotation.

Metabotropic glutamate receptors are a major class of excitatory amino acid receptors. Eight metabotropic glutamate receptors subtypes have been cloned and have been classified into three groups based on their amino acid sequence homology, effector systems, and pharmacological profile. Previous results have shown that striatal group I metabotropic glutamate receptor stimulation produces vigorous contralateral rotation in intact rats, thought to be due to increased striatal dopamine release. Examination of FOS-like immunoreactivity and local cerebral glucose metabolism suggests that this occurs secondary to activation of the subthalamic nucleus. We sought to determine the contribution of dopamine by examining metabotropic glutamate receptor agonist-induced rotation in rats following acute dopamine depletion by reserpine/alpha-methyl-para-tyrosine treatment, or chronic dopamine depletion by 6-hydroxydopamine treatment. In unilateral 6-hydroxydopamine lesioned rats, the group I metabotropic glutamate receptor agonist (RS)-3,5-dihydroxyphenylglycine induced contralateral rotation with a coincident increase in striatal 3,4-dihydroxyphenylacetic acid. The rotation was attenuated by the group I antagonist 1-aminoindan-1,5-dicarboxylate. Examination of FOS-like immunoreactivity and [14C]2-deoxyglucose uptake in chronically dopamine depleted rats also revealed similar patterns to those seen previously in intact rats. However, acutely dopamine depleted rats do not exhibit metabotropic glutamate receptor agonist-induced rotation and show a different pattern of [14C]2-deoxyglucose uptake, with no increase in glucose utilization in the intermediate and deep layers of the superior colliculus. These results suggest that there are compensatory changes under conditions of chronic dopamine denervation which permit metabotropic glutamate receptor agonist-induced rotation to occur, which may include dopamine receptor supersensitivity, increased dopamine turnover, and/or changes in sensitivity of striatal group I metabotropic glutamate receptors. The group III metabotropic glutamate receptor agonist L-(+)-2-amino-4-phosphonobutyrate induced contralateral rotation in 6-hydroxydopamine lesioned rats, while it had no effect in intact rats. Additionally, examination of FOS-like immunoreactivity revealed a distinct pattern following L-(+)-2-amino-4-phosphonobutyrate administration in 6-hydroxydopamine lesioned versus intact rats. These results suggest that there is a change in the effect of striatal group III stimulation under conditions of dopamine depletion.

3,4-Dihydroxyphenylacetic Acid↗