Striatal dopamine turnover during treadmill running in the rat: Relation to the speed of running

HATTORI, S., M. NAOI AND H. NISHINO. Striatal dopamine turnover during treadmill running in the rat: Relation to the speed of running. BRAIN RES BULL 35(1) 41–49, 1994.—To evaluate the physiological action of Striatal dopamine (DA) in exercise, rats were trained to run on a straight treadmill. Extracellular DA and its metabolites, dihydroxyphenylacetic acid (DO-PAC), and homovanillic acid (HVA) were measured by in vivo microdialysis, and striatal tissue tyrosine hydroxylase (TH) activity and monoamine oxidase (MAO) activity were measured using high performance liquid chromatography (HPLC) and spectrophotometer. DA turnover was increased by running, and the increase in DOPAC and HVA was closely related to the speed of running, while the increase in DA had no relationship to the speed. The threshold for the increase in DA, DOPAC, and HVA was between 300 and 660 cm/min. Striatal tissue TH activity was elevated up to 135% of basal values after the rats were trained for 7 days to run at 1800 cm/min. Just after running for 20 min, there was a further increase to 180%. These values became 150% and 90% of basal values at 2 h and 6 h, showing a similar time course as DA detected by microdialysis. MAO-B activity increased up to 160% of basal values after 7 days training but decreased to 130% and 110% just after and 2 h after running, then increased to 145% 6 h after running. MAO-A showed a similar variation as MAO-B. These data suggest that both the synthesis and metabolism of DA have a close relationship with physical exercise and might contribute to adjusting extracellular DA levels within an adequate range in response to exercise intensity.     

Hippocampal asymmetry in the behavioral responses to the 5-HT1A receptor agonist 8-OH-DPAT

The present study examined the behavioral responses of rats to unilateral and bilateral injections of the selective serotonin 1A (5-HT1A)-receptor agonist 8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT) 1 μg into the hippocampal CA1 area of male Wistar rats. 8-OH-DPAT increased locomotor activity, which was most pronounced with injections into the left hippocampus. The agonist impaired learning and memory (shuttle-☐), especially when injected into the right hippocampus. The elevated plus-maze experiments showed that neither left nor right nor bilateral hippocampal injections of 8-OH-DPAT produced any anxiogenic effect. However, with Vogel's conflict test, right injections of 8-OH-DPAT produced anxiety. The present study has revealed hippocampal asymmetry in the behavioral responses to the 5-HT1A-receptor agonist 8-OH-DPAT.     

Inhibition of nitric oxide synthase does not block the development of sensitization to the behavioral activating effects of amphetamine

Pretreatment with the nitric oxide (NO) synthase inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME), a competitive blocker of NO production, did not interfere with the development of sensitization to the behavioral activating effects of amphetamine (AMPH). On five pre-exposure sessions, at 3-day intervals, rats were given two i.p. injections, either 50 mg/kgL-NAME 30 min prior to 1.5 mg/kgD-AMPH sulfate, saline and AMPH,L-NAME and saline, or saline only.L-NAME reduced the levels of activity recorded during the pre-exposure session but had no effect on the degree of sensitization shown to a challenge injection of 0.5 mg/kg AMPH given 10 days later. A separate study using in vivo microdialysis showed that pretreatment withL-NAME did not alter AMPH-stimulated dopamine release in nucleus accumbens.     

The action of 5-HT on calcium-dependent potassium channels and on the spinal locomotor network in lamprey is mediated by 5-HT1A-like receptors

5-HT has a powerful modulatory action on the firing properties of single neurons as well as on locomotor activity. In lamprey, 5-HT increases the neuronal firing frequency in spinal neurons by reducing the conductance in Ca²⁺-dependent K⁺ channels (K_Ca) underlying the slow afterhyperpolarization (sAHP), and it also lowers burst frequency of the spinal locomotor network. To elucidate which type of 5-HT receptor mediates these effects, different specific receptor agonists and antagonists were applied during intracellular current lamp recordings and during NMDA-induced fictive locomotion in the lamprey spinal cord in vitro preparation. The 5-HT_1A receptor agonist 8-OH-DPAT ((±)-8-hydroxy-dipropylaminotetralin hydrobromide), the 5-HT₁ receptor agonist 5-CT (5-car☐yamidotryptamine maleate) and the 5-HT₂ receptor agonist α-CH₃-5-HT (α-methylserotonin maleate) all reproduced the actions of 5-HT at both the cellular and the network levels. The effects of all agonists were completely or partially blocked by the 5-HT_1A and 5-HT₂ receptor antagonist spiperone (spiroperidol hydrochloride) while selective 5-HT₂ receptor antagonists were ineffective. The selective 5-HT_1A receptor antagonist S(−)-UH301 (S(−)-5-fluoro-8-hydroxy-dipropylaminotetralin hydrochloride) also counteracted the effect of 5-HT on the sAHP. 5-HT₃ and 5-HT₄ receptor agonists and antagonists were without effects. The intracellular coupling mechanism was not sensitive to pertussis toxin nor to the cAMP dependent protein kinase blocker (Rp)-cAMPS. These results indicate that the intracellular coupling mechanism is not likely to be due to a down regulation of adenylate cyclase activity or through a direct modulation of K⁺ channels, as is common for 5-HT₁ receptors. The present results taken together with previous data indicates that the receptor responsible for the effects of 5-HT on the sAHP, and on the locomotor pattern generator in lamprey shares certain features, but is not identical to the mammalian 5-HT_1A receptor.     

Hippocampal theta activity related to elicitation and inhibition of approach locomotion

This study determined if the hippocampal theta rhythm showed phase relationships or changes in amplitude and frequency with the onset of stimuli and locomotion in a task in which auditory cues initiated and suppressed approach locomotion. Rats with electrodes in the dorsal hippocampus lapped at a milk dipper and were presented a tone which predicted the delivery of a food pellet. In some trials the pellet cue tone was negated by 60-Hz clicks beginning 0.3 s after onset, and no pellet was delivered. A video capture system (20-ms sampling) synchronized to the hippocampal recording system (10-ms sampling) was used to determine the onset of locomotor approach to the pellet area. The findings failed to support proposals that phase-related mechanisms play a role in encoding and retrieval of movement-related information. Neither the pellet cue nor the negating cue reset the theta rhythm, and they did not produce differential evoked potentials. During milk lapping, theta amplitude increased in the 1/2 s prior to all pellet cues regardless of their locomotor effect. Frequency also rose but only when a non-negated pellet elicited short-latency locomotion. During locomotor execution, theta peak amplitude peaked earlier than theta frequency by approximately one period. In general during performance of this task, increasing theta amplitude reflected a general preparation to process the cue and increasing theta frequency reflected the readiness to respond to the cue with locomotion.     

The relationship between hippocampal EEG theta activity and locomotor behaviour in freely moving rats: effects of vigabatrin

The relationship between hippocampal electroencephalogram (EEG) theta activity and locomotor speed in both spontaneous and forced walking conditions was studied in rats after vigabatrin injection (500 mg/kg i.p.). Vigabatrin increased the percentage of time that rats spent being immobile. During spontaneous walking in the open field, the speed of locomotion was increased by vigabatrin, while theta peak frequency was decreased. Vigabatrin also reduced the theta peak frequency during forced (speed controlled) walking. There was only a weak positive correlation (r=0.22) between theta peak frequency and locomotor speed for the saline condition. Furthermore, vigabatrin abolishes the weak relationship between speed of locomotion and theta peak frequency. Vigabatrin and saline did not differ in the slope of the regression line, but showed different offset points at the theta peak frequency axis. Thus, other factors than speed of locomotion seem to be involved in determination of the theta peak frequency.     

Expected and unexpected head yaw movements result in different modifications of gait and whole body coordination strategies

During locomotion we routinely make voluntary head movements, similar to those made during steering tasks, in order to scan our environment and obtain information about objects in the environment and our proximity to these objects. Given the importance that head segment orientation during locomotion has received in the recent literature, two studies were designed to investigate responses following a voluntarily generated and an unexpected, externally applied head turn. During a voluntary head turn, an efferent copy of the head movement could cancel the sensory effects of the head turn, effectively isolating the movement response to that segment. Alternatively, if the steering synergy is a part of our motor repertoire, as has been suggested, movement of the head could automatically release a steering synergy of segmental control and coordination. A unique head mounted air-jet apparatus, designed and developed at the University of Waterloo, was used for both studies to ensure that auditory stimuli and the physical presence of the apparatus on the head were similar for participants of the two experiments. During certain points in the gait cycle, this device was triggered and a short burst of compressed air (350 ms) was released to cue participants to make a voluntary head turn (Experiment 1). The same device was triggered in Experiment 2; however, in this experiment compressed air was released for a longer duration (1,500 ms) which resulted in an unexpected and quick turn of the participants head to either the left or right. In these experiments, vision was also manipulated in certain trials with liquid crystal display glasses that occluded vision for the duration of the head turn. Data from the first experiment indicates that a subset of the steering synergy previously observed is released following the voluntary head movement; however, the travel trajectory path is preserved, suggesting that sensory input resulting from the head movement is partially nullified by the central nervous system. Overall safety is ensured by maintaining the same travel path. In the second experiment, an unexpected perturbation was applied to the head during locomotion to determine how the absence of an efferent copy of the movement pattern influences the level of control over body segments during locomotion. Whole body responses similar to those observed during steering tasks were observed following application of this unexpected head perturbation. It is proposed that the CNS interprets an unexpected yaw movement of the head as a change in the frame of reference, and global modifications of the walking trajectory, similar to that observed during steering tasks, are made in the perceived new direction of travel. Collectively this work extends our understanding of how the CNS establishes a head based orientation frame for locomotion. The CNS interprets and integrates anticipated and unexpected changes in sensory information from the head segment and subsequently modifies locomotion patterns according to the perceived whole body orientation in space. The sequence of control following these head movements appears to be part of a movement repertoire that is not immutable; maintaining whole body stability during locomotion is paramount.     

Neural responses in multiple basal ganglia regions during spontaneous and treadmill locomotion tasks in rats

To investigate the role of basal ganglia in locomotion, a multiple-channel, single-unit recording technique was used to record neural activity simultaneously in the dorsal lateral striatum (STR), globus pallidus (GP), subthalamic nucleus (STN) and substantia nigra pars reticulata (SNr) during spontaneous and treadmill locomotion tasks in freely moving rats. Active and quiescent phases appeared alternately in a spontaneous movement session that lasted 60 min. Principal component analysis of the ensemble neural activity from each region revealed a close correlation with spontaneous motor activity. Most of the neurons in these four basal ganglia areas increased their firing rates during the active phase. In the treadmill locomotion task, the firing rates of neurons in all recording areas, especially in the STN, increased significantly during locomotion. In addition, neural responses related to tone cue, initiation and termination of treadmill were observed in a subset of neurons in each basal ganglia region. Detailed video analysis revealed a limb movement related neural firing, predominantly in the STR and the GP, during treadmill walking. However, the proportion of neurons exhibiting limb movement related firing was significantly greater only in the STR. A few neurons in the STR (4.8%) and the GP (3.4%) discharged in an oscillatory pattern during treadmill walking, and the oscillatory frequency was similar to the frequency of the step cycle. This study demonstrates a variety of neural responses in the major basal ganglia regions during spontaneous and forced locomotion. General activation of all major basal ganglia regions during locomotion is more likely to provide a dynamic background for cortical signal processing rather than to directly control precise movements. Implications of these findings in the model of basal ganglia organization are discussed.     

Locomotor adaptations for changes in the slope of the walking surface

The goal of this study was to examine the transition of walking from a level surface onto different inclined surfaces. Kinematic data of limb and trunk segments were recorded from individuals as they approached and stepped onto four different ramped surfaces (slopes=3°, 6°, 9°, 12°). This transition introduced significant adaptations to the swing limb trajectory that were evident in even the lowest ramp condition and appear to be scaled to the ramp inclination although the nature of this scaling seemed to change between the 6° and 9° conditions. An increased forward pitch of the trunk orientation during all ramp conditions was initiated early on during the preceding stance phase on level ground. The swing limb modification essentially consisted of a two-stage response. The initial response of the limb trajectory changes was not specific to the degree of inclination but later changes were dependent on the ramp condition. The initial response is to ensure a safe toe clearance as the foot approaches the edge of the ramp and then later modifications provide the appropriate positioning of the limb to prepare for an elevated foot contact. Early changes were actively produced through an increased pull-off by the hip flexors and an elevation of the swing limb by the active muscle control of the stance limb. Ankle dorsiflexion also appears to have a supporting role increasing toe clearance. Absorption at the hip and knee during later swing contribute to control and position the limb in preparation for foot contact. These strategies were similar to those adopted for step changes in the level of the walking surface where there are similar demands of the quickly moving the limb forward and upward, however, the positioning of the limb for new angled landing surface requires further adaptations.