Role of potassium channels in the antinociception induced by agonists of alpha2-adrenoceptors.
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1. The effect of the administration of pertussis toxin (PTX) as well as modulators of different subtypes of K+ channels on the antinociception induced by clonidine and guanabenz was evaluated in the mouse hot plate test. 2. Pretreatment with pertussis toxin (0.25 microg per mouse i.c.v.) 7 days before the hot-plate test, prevented the antinociception induced by both clonidine (0.08-0.2 mg kg(-1), s.c.) and guanabenz (0.1-0.5 mg kg(-1), s.c.). 3. The administration of the K(ATP) channel openers minoxidil (10 microg per mouse, i.c.v.), pinacidil (25 microg per mouse, i.c.v.) and diazoxide (100 mg kg(-1), p.o.) potentiated the antinociception produced by clonidine and guanabenz whereas the K(ATP) channel blocker gliquidone (6 microg per mouse, i.c.v.) prevented the alpha2 adrenoceptor agonist-induced analgesia. 4. Pretreatment with an antisense oligonucleotide (aODN) to mKv1.1, a voltage-gated K+ channel, at the dose of 2.0 nmol per single i.c.v. injection, prevented the antinociception induced by both clonidine and guanabenz in comparison with degenerate oligonucleotide (dODN)-treated mice. 5. The administration of the Ca2+-gated K+ channel blocker apamin (0.5-2.0 ng per mouse, i.c.v.) never modified clonidine and guanabenz analgesia. 6. At the highest effective doses, none of the drugs used modified animals' gross behaviour nor impaired motor coordination, as revealed by the rota-rod test. 7. The present data demonstrate that both K(ATP) and mKv1.1 K+ channels represent an important step in the transduction mechanism underlying central antinociception induced by activation of alpha2 adrenoceptors. (+info)
Concurrent performance of motor tasks and processing capacity in patients with schizophrenia.
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Any task is carried out more successfully if we allocate undivided attention to it, but as demands on attentional capacity increase-for example, in concurrent or dual task conditions-performance on attended tasks becomes more impaired. Patients with schizophrenia show impaired performance on tasks requiring high levels of attentional capacity. This study examines performance of 11 patients with schizophrenia and 13 normal controls on two motor tasks (placing pegs in a pegboard and repetitive index finger tapping) under unimanual, bimanual, and dual task conditions. The patients with schizophrenia placed fewer pegs and had reduced tapping speed in unimanual and bimanual conditions. However, the decrement in bimanual performance as a percentage of unimanual performance was not significantly different for the patients and controls on either the pegboard or tapping tasks. By contrast, under dual task conditions, the performance of the patients with schizophrenia in peg placement actually improved relative to the unimanual pegboard task, whereas tapping performance deteriorated compared with the unimanual tapping, a decrement that was significantly greater for the patients. Thus the improvement in the visually guided pegboard task was at the expense of the repetitive tapping task. These results are discussed in terms of an impairment of self initiated movement with general sparing of externally triggered movements in schizophrenia and the role of frontostriatal loops in this process. (+info)
Characterization of neuropeptide Y-induced feeding in mice: do Y1-Y6 receptor subtypes mediate feeding?
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The stimulation of food consumption after i.c.v. administration of various neuropeptide Y (NPY) receptor agonists was examined in CD-1 mice. These agonists, including endogenous peptides NPY, peptide YY (PYY), and pancreatic polypeptide, as well as several N-terminal truncated and synthetic peptides that are prototypic receptor agonists at Y1-Y6 NPY receptors ([Leu31Pro34]NPY, NPY2-36, NPY3-36, NPY13-36, PYY3-36, Pro34PYY, and D-Trp32NPY), showed varying abilities to elicit food consumption such that PYY > NPY2-36 = NPY = PYY3-36 > Pro34PYY > NPY3-36 >> [Leu31Pro34]NPY > NPY13-36 = D-Trp32NPY = pancreatic polypeptide. Published reports have suggested that NPY-induced feeding is mediated via the Y1 or the Y5 receptor subtypes. However, the relative ability of the various peptide analogs to elicit feeding differed from the relative ability of these peptides to bind to cloned Y1-Y6 receptors. The effects of prototypic Y1 receptor antagonists on NPY-induced feeding were also evaluated after i.c.v. administration. GR231118 (1229U91), a peptide Y1 antagonist, did not block NPY-induced feeding at the doses tested. BIBP3226, a nonpeptide Y1 receptor antagonist, as well as its opposite enantiomer, BIBP3435, which is inactive at Y1 receptors, blocked feeding elicited by NPY, [Leu31Pro34], or PYY at doses that did not cause overt behavioral dysfunction. The lack of effects with GR231118 and the nonstereoselective effects of BIBP3226 suggested that NPY-induced feeding in mice was not mediated via the Y1 receptor. Thus, by using currently available prototypic peptide NPY receptor agonists for Y1-Y6 receptors and peptide and nonpeptide Y1 receptor antagonists GR231118 and BIBP3226, the mediation of NPY-induced feeding cannot be unequivocally attributed to any one of the known NPY receptors. It is possible that NPY-induced feeding is mediated either by a combination of more than one NPY receptor subtype or by a unique NPY receptor subtype. Additional subtype-selective receptor antagonists, when available, will help to clarify this issue further. (+info)
The role of the hippocampus in auditory processing studied by event-related electric potentials and magnetic fields in epilepsy patients before and after temporal lobectomy.
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To clarify the relationship between the hippocampus and the event-related responses in auditory information processing, we recorded event-related potentials (ERPs) and event-related magnetic fields (ERFs) associated with the auditory oddball paradigm in 12 patients with temporal lobe epilepsy before and after surgical treatment, and in eight age-matched healthy volunteers. Lesions in the patients were hippocampal sclerosis (8), cyst (2), cavernoma (1) and calcified arteriovenous malformation (1), all in the unilateral temporal lobe. Standard temporal lobectomy (8), selective amygdalohippocampectomy (2), selective hippocampectomy (1) and inferior lateral temporal resection (1) were carried out. ERPs were recorded in nine patients before surgery, in all 12 patients after surgery, and in all normal subjects. P300 was maximal at Pz in the patients both before and after surgery, and in normal subjects. The peak latency and amplitude of P300 measured at Pz in the patients either before or after surgery did not differ significantly from those in normal subjects. After surgery, only the amplitude of P300 over the anterior and mid-temporal area on the resected side was attenuated, while it was symmetric before surgery regardless of the side of epileptogenic focus. ERFs were recorded in three patients before surgery and in six normal subjects by using a whole-head neuromagnetometer. ERFs in response to the target stimuli at a latency of approximately 400 ms were recognized at the anterior, middle and posterior lateral channels on each hemisphere (M400). The latency and dipole moments for M400 did not differ significantly between the patients before surgery and the normal subjects. As a result of analysis using the time-varying multidipole model, three dipoles for M400 were estimated in two patients in whom ERFs were available before surgery for the analysis, and in normal subjects: mesial temporal area, superior temporal area and inferior parietal area on each hemisphere. After surgery, in four out of six patients in whom ERFs were recordable, M400 at the anterior temporal channels on the resected side disappeared, and the activity in the affected mesial temporal area was lost. In one patient who underwent inferior lateral temporal resection, M400 waveforms and its sources were preserved in all regions. There were no significant differences in the latency and dipole moments of the unaffected source of M400 before versus after surgery. These results suggest that the hippocampus contributes to the scalp-recorded P300 only at the corresponding anterior temporal region, and does not influence its general waveform and predominant distribution over the scalp. (+info)
School attainments in children with congenital hypothyroidism detected by neonatal screening and treated early in life.
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OBJECTIVE: Evaluation of school attainments in children with congenital hypothyroidism (CH) detected by neonatal screening and treated early in life. PATIENTS AND METHODS: Text comprehension, mathematics, reading, writing and verbal and spatial memory, as indices of school learning, were evaluated in nineteen 5- to 10-year-old children with CH attending nursery or elementary school. l-Thyroxine substitution (starting dose 8-10 microg/kg body weight per day) was initiated at a mean age of 30+/-10 days of life. The control group included 298 unaffected children matched with the CH children for age and school grade. Thirty per cent of controls were classmates of CH children. Intelligence quotients (IQ), language performances and motor development were evaluated in CH children at age 5 years, and were related to their school attainments. School performances of CH children were also compared with their neonatal serum thyroxine (T4) concentration, and with the social-cultural level of the family. RESULTS: Four out of 19 (21%) children with CH, 3 in the nursery and 1 in the elementary school, displayed a generalized learning disorder. Symbol copy, geometric copy, phrase repetition, dictation writing and spontaneous writing were particularly defective in nursery school CH children, while orthographic error recognition was defective in elementary school CH children. School learning disorders in CH children were significantly correlated with a borderline-low IQ, poor language performances and a low social-cultural level of the family, but not with motor skills or neonatal T4 concentration. CONCLUSION: School attainments of early treated CH children were within the normal range in most affected cases. However, about 20% of CH children, most of them attending nursery school, showed a generalized learning disorder. Low IQ scores and poor language performances at age 5 years were associated with defective learning, mainly in CH children living in a poor social-cultural environment. In this subset of CH children, prompt initiation of speech and psychomotor rehabilitation therapy is recommended in order to prevent subsequent school learning disorders. (+info)
Presupplementary motor area activation during sequence learning reflects visuo-motor association.
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In preceding studies (Hikosaka et al., 1996; Sakai et al., 1998) we have shown that the presupplementary motor area (pre-SMA), an anterior part of the medial premotor cortex, is active during visuo-motor sequence learning. However, the paradigm required the subjects first to acquire correct visuo-motor association and then to acquire correct sequence, and it was still unknown which of the two processes the pre-SMA is involved in. To further characterize the role of pre-SMA, we have conducted another series of functional magnetic resonance imaging experiments using three learning paradigms. The three were the same in that they involved a visuo-motor association component, but they differed in terms of the involvement of sequential components; one involved no sequence learning, whereas the other two involved learning of motor sequence or perceptual sequence. Comparison of the learning conditions with the any-order button press condition revealed pre-SMA activation in all three paradigms. The pre-SMA activation remained unchanged during learning of visuo-motor associations but decreased during learning of sequences, suggesting that the pre-SMA is related to visuo-motor association rather than sequence. The decrease of pre-SMA activation in the sequential paradigms may reflect the process by which individual visuo-motor associations were replaced by the formation of sequential procedural memory, which occurs outside the pre-SMA. Thus activation of the pre-SMA was related to the extent to which the task performance depended on conscious visuo-motor associations. (+info)
Short- and long-term consequences of canal plugging on gaze shifts in the rhesus monkey. I. Effects on gaze stabilization.
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Short- and long-term consequences of canal plugging on gaze shifts in the rhesus monkey. I. Effects on gaze stabilization. To study the contribution of the vestibular system to the coordinated eye and head movements of a gaze shift, we plugged the lumens of just the horizontal (n = 2) or all six semicircular canals (n = 1) in monkeys trained to make horizontal head-unrestrained gaze shifts to visual targets. After the initial eye saccade of a gaze shift, normal monkeys exhibit a compensatory eye counterrotation that stabilizes gaze as the head movement continues. This counterrotation, which has a gain (eye velocity/head velocity) near one has been attributed to the vestibuloocular reflex (VOR). One day after horizontal canal plugging, the gain of the passive horizontal VOR at frequencies between 0.1 and 1.0 Hz was <0.10 in the horizontal-canal-plugged animals and zero in the all-canal-plugged animal. One day after surgery, counterrotation gain was approximately 0.3 in the animals with horizontal canals plugged and absent in the animal with all canals plugged. As the time after plugging increased, so too did counterrotation gain. In all three animals, counterrotation gain recovered to between 0.56 and 0.75 within 80-100 days. The initial loss of compensatory counterrotation after plugging resulted in a gaze shift that ended long after the eye saccade and just before the end of the head movement. With recovery, the length of time between the end of the eye saccade and the end of the gaze movement decreased. This shortening of the duration of reduced gain counterrotation occurred both because head movements ended sooner and counterrotation gain returned to 1.0 more rapidly relative to the end of the eye saccade. Eye counterrotation was not due to activation of pursuit eye movements as it persisted when gaze shifts were executed to extinguished targets. Also counterrotation was not due simply to activation of neck receptors because counterrotation persisted after head movements were arrested in midflight. We suggest that the neural signal that is used to cause counterrotation in the absence of vestibular input is an internal copy of the intended head movement. (+info)
Muscimol-induced inactivation of monkey frontal eye field: effects on visually and memory-guided saccades.
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Muscimol-induced inactivation of the monkey frontal eye field: effects on visually and memory-guided saccades. Although neurophysiological, anatomic, and imaging evidence suggest that the frontal eye field (FEF) participates in the generation of eye movements, chronic lesions of the FEF in both humans and monkeys appear to cause only minor deficits in visually guided saccade generation. Stronger effects are observed when subjects are tested in tasks with more cognitive requirements. We tested oculomotor function after acutely inactivating regions of the FEF to minimize the effects of plasticity and reallocation of function after the loss of the FEF and gain more insight into the FEF contribution to the guidance of eye movements in the intact brain. Inactivation was induced by microinjecting muscimol directly into physiologically defined sites in the FEF of three monkeys. FEF inactivation severely impaired the monkeys' performance of both visually guided and memory-guided saccades. The monkeys initiated fewer saccades to the retinotopic representation of the inactivated FEF site than to any other location in the visual field. The saccades that were initiated had longer latencies, slower velocities, and larger targeting errors than controls. These effects were present both for visually guided and for memory-guided saccades, although the memory-guided saccades were more disrupted. Initially, the effects were restricted spatially, concentrating around the retinotopic representation at the center of the inactivated site, but, during the course of several hours, these effects spread to flanking representations. Predictability of target location and motivation of the monkey also affected saccadic performance. For memory-guided saccades, increases in the time during which the monkey had to remember the spatial location of a target resulted in further decreases in the accuracy of the saccades and in smaller peak velocities, suggesting a progressive loss of the capacity to maintain a representation of target location in relation to the fovea after FEF inactivation. In addition, the monkeys frequently made premature saccades to targets in the hemifield ipsilateral to the injection site when performing the memory task, indicating a deficit in the control of fixation that could be a consequence of an imbalance between ipsilateral and contralateral FEF activity after the injection. There was also a progressive loss of fixation accuracy, and the monkeys tended to restrict spontaneous visual scanning to the ipsilateral hemifield. These results emphasize the strong role of the FEF in the intact monkey in the generation of all voluntary saccadic eye movements, as well as in the control of fixation. (+info)