Waneen W. Spirduso

Tactile extinction: distinguishing between sensorimotor and motor asymmetries in rats with unilateral nigrostriatal damage.

Abstract We describe and demonstrate the usefulness of a reliable procedure for quantifying “sensorimotor” asymmetries in rats with nigrostriatal damage. Conventional tests, such as the popular Von Frey hair technique are sometimes inadequate in that positive responses are difficult to quantify, they are susceptible to subjective interpretation, and they require that the animal make head movements. Circling behavior has become established as a measure of asymmetrical nigrostriatal activity, but it does not measure stimulus-directed movement. One group of rats was given unilateral microinfusions of 6-OHDA into the nigrostriatal system which decreased levels of dopamine in the ipsilateral striatum and yieded an ipsilateral turning bias. Another group was given electrolytic lesions in the substantia nigra area, which yielded a severe contralateral circling bias. Small pieces of adhesive paper were applied to various parts of the limbs or snout and latencies to remove the stimuli were recorded. Because head and body movements were not required, assessment of stimulus-directed movement asymmetries could be quantified rapidly without the interference of stimulus-independent (“spontaneous”) postural and motor asymmetries. In the 6-OHDA-treated rats there was ipsilateral bias in stimulus-directed activity. Indeed, there was ipsilateral hyper-reactivity relative to sham controls. In rats with electrolytic nigra lesions, despite a strong contralateral “spontaneous” motor bias, there likewise was an ipsilateral bias in stimulus-directed movement, which could only be detected using the adhesive removal test. This similarity in stimulus-directed movement asymmetry between the two groups may reflect a common asymmetry in ascending dopaminergic pathways. The opposite circling bias following electrolytic nigra lesions may reflect differential damage to non-dopaminergic efferent projections. The bilateral adhesive removal (tactile extinction) test appears to permit the separate quantification of stimulus-directed and stimulus-independent movement asymmetries.

Reactive capacity: A sensitive behavioral marker of movement initiation and nigrostriatal dopamine function.

Thirty-two Long Evans male rats with sham operations or unilateral 6-OHDA-induced damage to meso-telencephalic dopaminergic neurons were evaluated on a reactive capacity task that demanded high speed movement initiation. The task required lever manipulation to avoid signalled shock. The interval between the warning and the shock was incrementally reduced. A one-sleeved vest provided the opportunity to measure movement initiation of each limb independently. Extent of lesion was assessed by [3H]DA uptake, [3H]spiroperidol binding, or DA levels. Movement initiation latencies for each forelimb were found to be linearly related to interhemispheric striatal DA asymmetry induced by microinjections of 6-OHDA. Even those lesions resulting in small to moderate decreases in DA function, including deficits causing no chronic posture or sensory asymmetries, resulted in reactive capacity deficits and greatly slowed reaction time in the paw contralateral to the lesion. Following severe lesions, small yet substantial deficits were also seen in ipsilateral paw performance, which may be related to DA depletions found in the non-lesioned striatum. Thus, a reactive capacity task which requires the animal to react with maximal speed appears to be a potentially good index of nigrostriatal dopamine integrity even when the depletion is not severe.

Endurance training effects on striatal D2 dopamine receptor binding and striatal dopamine metabolites in presenescent older rats

Endurance training is associated with higher binding of 3H-spiperone to striatal D2 dopamine receptors of rats sacrificed 48 h following the last exercise bout (Gilliam et al. 1984). In the present study we investigated the effects of endurance training in presenescent older rats on the relationship between steady-state levels of DA and its metabolites in striatum versus the affinity and density of striatal D2 DA receptors. Citrate synthase activity of the gastrocnemius-plantaris muscle was 29.06±2.27 μmole/g wet wt in 21-month-old trained rats versus 22.88±1.13 μmole/g wet wt in 21-month-old untrained animals.DOPAC levels and DOPAC/DA ratios were greater in the old controls. Endurance training was associated with lower DOPAC levels in the 21-month-old animals. Thus, endurance training may postpone selectively changes in DA metabolism over a portion of the lifespan.As expected, the number of D2 DA binding sites was reduced with age (6 months Bmax:429±21 fmoles/mg protein; 21 months:355±20) with no change in affinity. The Bmax of old runners was significantly higher (457 ± 38 fmoles/mg protein) than that of old controls. Thus, endurance training appears to exert a protective effect on D2 dopamine receptors during the lifespan. Taken together, the present results suggest that there may be a possible reciprocal relationship between changes in DA metabolites and DA binding as a function of exercise in presenescent older rats, and that endurance training may decelerate the effects of age both on nigrostriatal dopamine neurons and on striatal D2 dopamine receptors during a portion of the lifespan.

Long-Term Effects of Three Multicomponent Exercise Interventions on Physical Performance and Fall-Related Psychological Outcomes in Community-Dwelling Older Adults: A Randomized Controlled Trial

To determine the long‐term effects of three strength and balance exercise interventions on physical performance, fall‐related psychological outcomes, and falls in older people.

The effects of exercise training on [3H]-spiperone binding in rat striatum

Thirty male Sprague-Dawley rats 100 days of age were divided into three groups: interval trained, endurance trained, and pair-weighted controls. Both trained groups ran up to one hour per day, 6 days per week for 12 weeks. The interval trained group ran up to 20 repeat intervals at 54 meters per minute for 30 seconds, while the endurance trained group ran at 27 meters per minute for 60 minutes. The animals were sacrificed, and the effects of aerobic training were documented by measuring cytochrome oxidase activity in the mixed quadriceps muscles. The cytochrome oxidase activity of the interval and endurance trained groups increased 49%, and 31% respectively, above the control group. [3H]-spiperone was used to label dopamine receptors in the striatum. The endurance group was not significantly different from the interval group in [3H]-spiperone receptor binding, so the two exercise groups were combined to form one group of runners. The runners had significantly higher [3H]-spiperone receptor binding than the controls, F(1,26) = 4.87, p less than 0.05. The mean and standard error for receptor binding was 89 +/- 13 fmoles/mg protein for the runners and 60 +/- 5 fmoles/mg protein for the controls.

Reaction time and nigrostriatal dopamine function: the effects of age and practice

Normal aged and Parkinsonian individuals lose the ability to initiate movements rapidly (increased reaction time) in parallel with changes in the nigrostriatal dopamine (DA) system. However, the ability of these individuals to improve their reaction time with practice has not been adequately assessed. We have developed a rodent model of human reaction time in which reaction time performance correlates highly with neurochemical measures of nigrostriatal DA integrity. In the present report, 15 young and 10 old male Sprague-Dawley rats were conditioned in a reaction time task to release a lever quickly in response to external stimuli in order to avoid a mild footshock. In order to examine the effects of practice on this reaction time task, the young animals were tested for 5 days at 3, 6 and 9 months of age and the old animals were tested for 5 days at 18, 21, and 24 months of age. From this well-practiced task, reaction time response latencies were measured and compared to measures of nigrostriatal DA function (steady-state levels of DA and its metabolites, D2DA receptor affinity and density). The old animals were slower in response latencies than the young animals. These age differences in response latencies, however, disappeared after several days of testing at each of the 3 test sessions, so that the old animals were not significantly slower than the young animals on days 4 and 5 of each session. As expected, the old animals showed reduced striatal D2DA receptor density with no age differences in DA receptor affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise and the Aging Brain

Abstract The clinical landmarks of an aging motor system closely resemble diseases of the extrapyramidal system, notably the basal ganglia. Similarly, mechanisms that appear to be related to one of these diseases, Parkinsons disease, also seem to be related to motor system aging. The nigrostriatal dopaminergic system, impaired in both Parkinsons disease and in aging, has been shown to be substantially involved in movement initiation. This involvement has been shown by analyzing nigrostriatal dopamine in fast vs slow responding animals, and by manipulating the dopaminergic system by pharmacological methods. Exercise may postpone the deterioration in response speed that is generally observed in the aged motor system, by maintaining the nigrostriatal dopamine system. This mechanism is suggested by differences in neurotransmitter function seen in exercise rats compared to sedentary rats, and in studies of dopamine metabolites obtained from exercised humans. These mechanisms suggest that an excellent physica...

Selective D1 and D2 dopamine receptor antagonists produce differential effects on reaction time in the rat

The purpose of this investigation was to determine whether selectively blocking D1 and D2 dopamine receptors produces a differential effect on the characteristics (speed and success) of the reaction time response in rats. Animals were shaped to release a lever in response to an auditory/visual stimulus to avoid mild foot shock. The selective D1 antagonist SCH 23390 (0, 70, and 100 micrograms/kg, IP) and the selective D2 antagonists spiperone (0, 1, and 10 micrograms/kg, IP) and haloperidol (0, 10, and 100 micrograms/kg, IP) were studied for their effects on successful avoidance and response latency. SCH 23390 impaired successful avoidance and increased response latencies in a dose-dependent manner. Spiperone and haloperidol also produced dose-related decreases in successful avoidance. In contrast to the dose-related increase in response latencies produced by SCH 23990, 1 microgram/kg spiperone and 10 micrograms/kg haloperidol significantly decreased the latencies of successful responses. Spiperone (10 micrograms/kg) had little effect on response latencies, while 100 micrograms/kg haloperidol increased them. The results of these experiments demonstrate that reaction time is differentially affected by selective dopamine receptor blockade and that the speed and success of reaction time responses can be independently modulated by D1 vs. D2 receptor activity.

Age and Practice Effects on Force Control of the Thumb and Index Fingers in Precision Pinching and Bilateral Coordination

Older women were less accurate and required more time in tracing a triangle template by controlling the force on spring levers with three different finger combinations: a one-hand precision pinching movement, a bilateral index finger movement, and a left index finger and right thumb combination. Older subjects were disproportionately less accurate than young subjects when required to decouple the pinching movement and control the index finger and thumb independently. Effects of practice were similar for both age groups, except that the elderly increased behavioral speed more from the first to the second day of practice. Explanations for the findings were based on neurosynergistic-intentional control interactions, visuospatial deficits in the elderly, and older subjects’ predisposition to perseverate.

Effects of chlorpromazine on escape and avoidance responses a closer look

While a wealth of evidence has implicated the nigrostriatal dopamine system in the initiation of movement, most or all of these movements have been in a conditioned avoidance framework, and on the order of 3-14 seconds in latency. It is proposed here that an elucidation of dopaminergic involvement in movement initiation requires a behavioral paradigm wherein experimental animals must rapidly and voluntarily respond to a stimulus to move (i.e., in less than 300 msec, paralleling human reaction time). Such a paradigm was developed and implemented in a re-analysis of earlier reports of chlorpromazine (CPZ) effects on escape from an avoidance of electric shock. Catecholaminergic or dopaminergic receptor blocking by CPZ resulted in clear impairment of the ability to initiate rapid avoidance movements, but in contrast to earlier work, some impairment of escape responses was also seen. Results are seen as further support for dopaminergic involvement in the initiation of voluntary movement.