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Phencyclidine and behavior: I. Sensory-motor function, activity level, taste aversion and water intake.

Phencyclidine (PCP) injections in rats at doses of 4 mg/kh increased activity level, which might have been a function of impaired habituation. At doses of 8 mg/kg PCP produced a marked reduction in activity level. At doses of 12 mg/kg and above there were profound disruptive effects in detection of odors, visual square and touch measures, and performance of placing reflexes requiring visuo-motor coordination, righting, grasping reflexes, and equilibrium. Decreases in water intake occurred only at higher dose levels of PCP (16 and 24 mg/kg). On a qualitative basis the changes observed in rats are similar to changes described for humans.

Animals↗

Basal ganglia motor function in relation to Hallervorden-Spatz syndrome.

Hallervorden-Spatz syndrome (HSS) is a degenerative neurologic disorder associated with progressive rigidity, dystonia, impaired voluntary movement, dysarthria, and mental deterioration. Pathologically, there is iron deposition in the basal ganglia, with destruction of basal ganglia output neurons. Recent advances in the understanding of basal ganglia functional anatomy and physiology make it possible to hypothesize how specific neural mechanisms relate to specific clinical manifestations of HSS. Experimental lesions of the basal ganglia output nucleic cause involuntary muscle contractions, similar to contractions observed in dystonia. A model of selection and suppression of competing motor patterns by the basal ganglia is presented in relation to the manifestations of damage to basal ganglia output neurons. It is hypothesized that the dystonia and other motor abnormalities seen in HSS can be attributed to degeneration of basal ganglia output neurons.

Basal Ganglia↗

Spinal cord implantation of avulsed ventral roots in primates; correlation between restored motor function and morphology.

Functional restitution following spinal cord implantation of avulsed ventral roots was assessed electromyographically and correlated with the morphology of the regenerated neural structures in primates. The C5-C8 ventral roots were avulsed from the spinal cord in seven Macaca fascicularis monkeys. In three animals the roots were immediately reimplanted into the ventrolateral part of the spinal cord. In two monkeys the avulsed roots were reimplanted with a delay of 2 months and in two control animals the roots were not reimplanted. There was substantial recovery of function after both immediate and delayed spinal cord implantation of the avulsed ventral roots. The population of neurons that had regenerated was larger than on the control side, indicating a rescue of cells after an immediate root implantation. Different functional types of neurons had been attracted to regrow axons to the implanted root as judged by their position in the ventral horn. Thus, neurons normally supplying antagonistic muscles, such as the triceps muscle, participated in the innervation of the biceps muscle. Functionally this deficient directional specificity was correlated to both spasticity and co-contractions among agonistic and antagonistic muscles. Occasional electromyographic signs of function occurred also in control animals where the avulsed roots had not been implanted. This recovery was found to depend on regrowth from the site of avulsion, within the pia mater among the leptomeningeal cells and to the avulsed roots. The acceptable functional dexterity regained due to corrective surgery is discussed in terms of neurotrophism and plasticity.

Animals↗

Testosterone improves motor function in Parkinson's disease.

In Parkinson's disease (PD) there is increasing evidence that sex steroids such as estradiol and testosterone modulate, either as a positive or negative effect, the clinical expression of a variety of movement disorders involving the nigrostriatum. Testosterone deficiency is common in the older male population and has an increased prevalence in parkinsonian patients. Testosterone therapy has been shown to improve the non-motor symptoms of PD but evidence for a direct effect of testosterone on motor symptoms is lacking. This case report demonstrates a significant improvement in the resting tremor and fine motor control after testosterone administration in a parkinsonian patient with testosterone deficiency (1 nmol/L). Motor symptom change was shown by serial assessment of the patient's handwriting, self-reporting using the Unified Parkinson's Disease Rating Scale and measurement of resting tremor amplitude by an accelerometer. The improvement in motor symptoms correlated with serum testosterone levels. The use of testosterone replacement in those men with decreased levels may improve the motor symptoms as well as increase general wellbeing.

Aged, 80 and over↗

Increased protein phosphorylation of cytoplasmic dynein results in impaired motor function.

Inhibition of serine/threonine protein phosphatases in rat hepatocytes by okadaic acid and microcystin increased the phosphorylation of several components of the cytoplasmic dynein complex. UV light/vanadate cleavage and Western blot analysis revealed that two of these components with molecular masses of approx. 400 kDa and 74 kDa were dynein heavy- and intermediate-chains respectively. This increased phosphorylation resulted in inhibition of dynein ATPase activity, and reduced motor-dependent avidity of endosomal/lysosomal membranes for microtubules.

Animals↗

Effects of unilateral subthalamic and pallidal deep brain stimulation on fine motor functions in Parkinson's disease.

Deep brain stimulation (DBS) is an effective treatment for selected patients with disabling Parkinson's disease (PD). The two main targets are the subthalamic nucleus (STN) and the globus pallidus internus (GPi), although it has not been established whether stimulation at one target is superior to the other. This prospective randomized study assessed the effects of unilateral DBS of the STN versus GPi on fine motor skills in 33 patients with advanced PD. Stimulation of either the STN (18 subjects) or GPi (15 subjects) in the off medication state significantly improved movement time and dexterity, but had little or no effect on reaction time. Overall, the extent of improvement did not differ between the two targets. The degree of improvement in movement time, but not dexterity, was correlated with the extent of preoperative medication responsiveness. Our findings suggest that DBS of the STN or GPi results in a similar improvement in hand movements at short-term follow-up. Preoperative medication responsiveness predicts improvement in some but not other motor tasks.

Adult↗

[Effect of parenterally administered protein hydrolysates on the motor function of the stomach and small intestine].

Intravenous administration of proteinic hydrolysates (caseine and aminopeptide hydrolysates) to dogs for a duration of 2 hours debars on active period in the fasting periodic activity of the stomach, this being attended by the stimulation of gastric secretion with pH changing from alkaline or neutral to acid reaction. Introduction of the caseine and aminopeptide hydrolysate did not cancell out the active period of the duodenal motoricity, though the frequency of contractions was somewhat below that in controls.

Animals↗

Sensori-motor function, gait patterns and falls in community-dwelling women.

Tests of vision, vestibular function, peripheral sensation, strength, reaction time, balance and gait were administered to 183 community-dwelling women aged 22-99 years. Walking speed, stride length and cadence declined with age with corresponding increases in stance duration and percentage of the stride in the stance phase. Visual acuity and contrast sensitivity, tactile and vibration sense in the lower limb, vestibular function (as assessed by the vestibular X Writing Test), quadriceps and ankle dorsiflexion strength and reaction time were significantly associated with all five gait parameters. Postural sway measures were associated with walking speed, stride length and percentage of the stride in the stance phase. Multiple regression analyses revealed seven sensori-motor measures as significant predictors for one or more of the gait parameters: low contrast visual acuity, tactile sensitivity, vibration sense, vestibular X-test writing performance, quadriceps strength, reaction time and sway. Quadriceps strength was included as a predictor variable for every gait parameter and in each case had the strongest beta weight. Women who fell on two or more occasions in a one-year prospective period had significantly reduced and more variable cadence and significantly increased stance duration (measured in absolute terms and as a percentage of stride) than those who did not fall or fell on one occasion only. The study findings elucidate the relative importance of specific physiological systems in the maintenance of normal gait and identify temporal gait measures that are associated with falling in older people.

Accidental Falls↗

Exercise and training to optimize functional motor performance in stroke: driving neural reorganization?

Neurorehabilitation is increasingly taking account of scientific findings. Research areas directing stroke rehabilitation are neurophysiology; adaptability to use and activity; biomechanics; skill learning; and exercise science (task, context specificity). Understanding impairments and adaptations enables a reappraisal of interventions-for example, changes in motor control resulting from impairments (decreased descending inputs, reduced motor unit synchronization), secondary soft tissue changes (muscle length and stiffness changes) are adaptations to lesion and disuse. Changes in interventions include increasing emphasis on active exercise and task-specific training, active and passive methods of preserving muscle extensibility. Training has the potential to drive brain reorganization and to optimize functional performance. Research drives the development of training programs, and therapists are relying less on one-to-one, hands-on service delivery, making use of circuit training and group exercise and of technological advances (interactive computerized systems, treadmills) which increase time spent in active practice. Emphasis is on skill training, stressing cognitive engagement and practice, aiming to increase strength, control, skill, endurance, fitness, and social readjustment. Rehabilitation services remain slow to make the changes necessary to upgrade environments, attitudes, and rehabilitation methodologies to those shown to be more scientifically rational and for which there is evidence of effectiveness.

Exercise Therapy↗

The selective dopamine D2 receptor antagonist raclopride discriminates between dopamine-mediated motor functions.

The actions on central dopamine (DA) mechanisms of raclopride, a new substituted benzamide, were studied by means of behavioural and biochemical methods in the rat. Raclopride blocked the in vitro binding of the dopamine D2 antagonist 3H-spiperone (IC50 = 32 nM), but not of the unselective D1 antagonist 3H-flupenthixol (IC50 greater than 100,000 nM) in rat striatum, and failed to inhibit striatal DA-sensitive adenylate cyclase in vitro (IC50 greater than 100,000 nM). Raclopride caused a dose-dependent increase in the DA metabolites HVA and DOPAC in the striatum and olfactory tubercle. Behavioural studies showed that raclopride discriminates between the motor behaviours induced by the DA agonist apomorphine. Thus, unlike haloperidol, raclopride blocked apomorphine-induced hyperactivity at considerably lower doses than those inhibiting oral stereotypies. Moreover, raclopride showed a high separation between the doses for blockade of apomorphine-induced hyperactivity and those inducing catalepsy in rats. Raclopride caused a dose-dependent blockade of the specific binding of 3H-spiperone and 3H-N-n-propylnorapomorphine (3H-NPA) in vivo at doses similar to those blocking the behavioural effects of apomorphine. The maximal blockade of 3H-spiperone binding in vivo was lower for raclopride than for haloperidol. Raclopride caused a greater inhibition of 3H-NPA than of 3H-spiperone in vivo binding in the striatum. It is suggested that the ability of raclopride to discriminate between different DA-mediated functions may be attributed to a preferential blockade of a subclass of functionally coupled dopamine D2 receptors in striatal as well as in extrastriatal brain regions in the rat.

Adenylyl Cyclases↗

Tachykinins in the gut. Part I. Expression, release and motor function.

The preprotachykinin-A gene-derived peptides substance P and neurokinin (NK) A are expressed in distinct neural pathways of the mammalian gut. When released from intrinsic enteric or extrinsic primary afferent neurons, tachykinins have the potential to influence both nerve and muscle by way of interaction with three different types of tachykinin receptor, termed NK1, NK2 and NK3 receptors. Most prominent among the effects of tachykinins is their excitatory action on gastrointestinal motor activity, which is seen in virtually all regions and layers of the mammalian gut. This action depends not only on a direct activation of the muscle through NK1 and/or NK2 receptors, but also on stimulation of excitatory enteric motor pathways through NK3 and/or NK1 receptors. In addition, tachykinins can inhibit motor activity by stimulating either inhibitory neuronal pathways or interrupting excitatory relays. A synopsis of the available data indicates that endogenous substance P and NKA interact with other enteric transmitters in the physiological control of gastrointestinal motor activity. Derangement of the regulatory roles of tachykinins may be a factor in the gastrointestinal dysmotility associated with infection, inflammation, stress and pain. In a therapeutic perspective, it would seem conceivable, therefore, that tachykinin agonists and antagonists are adjuncts to the treatment of motor disorders that involve pathological disturbances of the gastrointestinal tachykinin system.

Animals↗

Naltrexone: effects on motor function, speech, and activities of daily living in a patient with traumatic brain injury.

Evidence from many studies has suggested that endogenous opioid peptides participate in a number of pathophysiological responses to brain injury. This provides the rationale for the use of opioid antagonists for the enhancement of neural recovery after brain injury. A case is presented of an 18-year-old male who had loss of consciousness for 1 month after a severe brain injury. Three months of intensive rehabilitative therapies did not change his functional status. A trial of naltrexone was given while his performance in mobility, speech and overall Functional Independence Measure (FIM) scores were monitored. Results indicate an accelerated improvement in functional status and statistically improved FIM score.

Activities of Daily Living↗

Electrophysiological recording from neurons controlling sensory and motor functions of the esophagus.

Much work has been done in recent years to understand the functional roles of sensory neurons that regulate reflexes and sensations. Information about the response patterns of spinal dorsal horn and brain stem neurons associated with esophageal functions has become available by using electrophysiological techniques. These techniques allow understanding of response characteristics of neurons to various types of stimuli, neurotransmitters involved in excitation or inhibition of neurons, changes in response characteristics of neurons under pathological conditions, and the shape and size of a particular neuron in the central nervous system, as well as its projection to other areas of the brain. Response properties of primary afferent fibers in the vagus and thoracic sympathetic nerves have been studied in intact animal models by using single-fiber or extracellular microelectrode recording techniques. Recently, the single-fiber recording technique has been used in vitro in isolated esophagus-vagus nerve preparations. Recordings from the brain stem nuclei and thoracic spinal dorsal horn neurons also have examined the response characteristics of second-order neurons receiving afferent input from the esophagus. In the spinal cord, dorsal horn neurons responsive to esophageal distension also receive ipsilateral somatic input (ie, viscero-somatic convergence) from the upper thoracic area. These neurons exhibit sensitization of response after repeated noxious distension of the esophagus or instillation of irritant substances in the esophagus. In the nucleus ambiguus, neurons receiving input from the distal esophagus exhibit excitation to distension of the distal esophagus but undergo inhibition to midthoracic esophageal distension or to swallow. Neurons in the nucleus tractus solitarius receiving input from the distal esophagus exhibit 2 types of responses to proximal and distal esophageal distension. One type of response is a rhythmic firing synchronized with peristaltic contractions of the distal esophagus. This response undergoes inhibition in response to proximal distension. In addition, there is a second, nonrhythmic firing response that occurs both proximal and distal esophageal distension. This observation suggests that swallow-induced inhibition of the distal esophagus is controlled by the preganglionic motor neurons in the brain stem. Electrophysiological studies allow direct understanding of neuronal activities regulating esophageal functions. In vivo recording has an advantage for studying functional roles of the neurons in regulatory reflexes, whereas in vitro recording is useful for more accurate study of receptor pharmacology. Recordings from the central nervous system allow study of the neurotransmitters involved in neuronal function and the circuitry of different reflex mechanisms.

Deglutition↗