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Differential thermosensor control of thermoregulatory grooming, locomotion, and relaxed postural extension.

The rat displays three behaviors when surface and/or deep body temperatures rise above their normal levels: grooming, which spreads saliva over the fur to cool by evaporation; locomotion, which results in escape to a cooler environment; and relaxed postural extension, which reduces heat production by muscle activity and increases heat dissipation by increasing body surface area. Each of these behaviors can be elicited in pure or nearly pure form by localized warming of thermosensors in different brain areas. In addition, localized warming of superficial and deep peripheral thermosensors elicits grooming and locomotion, but little or no postural extension. Because of the marked differences in the behaviors induced by localized warming of different sets of thermosensors, it is concluded that sensors are linked to the effector mechanisms for these behaviors by relatively separate and independent pathways rather than a master controller through which sensory signals are integrated to produce a unitary error signal that drives all responses. When more generalized hyperthermia in natural heat stress situations affects mainly superficial thermosensors, as during the initial phase of exposure to ambient heat, grooming and locomotion are predominant and extension is absent or weak. When deep hyperthermia is predominant and superficial hyperthermia is relatively weak, as occurs after escape from ambient heat to thermoneutrality or during and following exercise in a thermally neutral environment, the resulting predominant activation of deep sensors elicits marked postural extension, but little or no grooming or locomotion. When both superficial and deep sensors are hyperthermic, as in the later stages of exposure to ambient heat, all three behaviors are present, although locomotion is somewhat greater and grooming is somewhat less than during predominantly superficial hyperthermia, and extension is somewhat less than during predominantly deep hyperthermia. As a consequence, grooming is maximal during predominantly superficial hyperthermia, locomotion during mixed deep and superficial hyperthermia, and extension during predominantly deep hyperthermia. It is concluded that the relatively fractionated control of the rat's thermoregulatory behaviors by different groups of central and peripheral thermosensors makes possible a differentiation of responses to different distributions of hyperthermia between superficial and deep sensors that optimizes cost-benefit trade-offs in different kinds of heat stress.

Animals↗

Augmented renal sympathetic nerve activity by central command during overground locomotion in decerebrate cats.

We examined whether the cerebrum is essential for producing the rapid autonomic adjustment at the onset of spontaneous overground locomotion. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), heart rate (HR), and electromyogram of the forelimb triceps brachialis were measured when freely moving, decerebrate cats spontaneously produced overground locomotion, supporting body weight. Decerebration was performed at the level of the precollicular-premammillary body. RSNA increased 95 +/- 14 impulses/s (68 +/- 10% of baseline value) at the onset of spontaneous locomotion, which was followed by rises in MAP and HR (7 +/- 1 mmHg and 18 +/- 2 beats/min, respectively). Concomitantly with the MAP rise, RSNA declined toward control values and then increased again during the subsequent period of locomotion. The same rapid increase in RSNA at the onset of locomotion was observed after sinoaortic denervation and vagotomy. It is concluded that some central site(s), other than the cerebrum and the rostral part of the diencephalon, can generate the centrally induced autonomic adjustment at the onset of spontaneous overground locomotion, which is independent of arterial baroreceptor and vagal afferents.

Afferent Pathways↗

Recovery of locomotion after ventral and ventrolateral spinal lesions in the cat. II. Effects of noradrenergic and serotoninergic drugs.

The effects of serotoninergic and noradrenergic drugs (applied intrathecally) on treadmill locomotion were evaluated in two adult cats subjected to a ventral and ventrolateral spinal lesion (T13). Despite the extensive spinal lesion, severely damaging important descending pathways such as the reticulo- and vestibulospinal tracts, both cats recovered quadrupedal voluntary locomotion. As detailed in a previous paper, the locomotor recovery occurred in three stages defined as early period, when the animal could not walk with its hindlimbs, recovery period, when progressive improvement occurred, and plateau period, when a more stable locomotor performance was observed. At this latter stage, the cats suffered from postural and locomotor deficits, such as poor lateral stability, irregular stepping of the hindlimbs, and inconsistent homolateral fore- and hindlimb coupling. The present study aimed at evaluating the potential of serotoninergic and/or noradrenergic drugs to improve the locomotor abilities in the early and late stages. Both cats were implanted chronically with an intrathecal cannula and electromyographic (EMG) electrodes, which allowed determination, under similar recording conditions, of the locomotor performance pre- and postlesion and comparisons of the effects of different drugs. EMG and kinematic analyses showed that norepinephrine (NE) injected in early and plateau periods improved the regularity of the hindlimb stepping and stabilized the interlimb coupling, permitting to maintain constant locomotion for longer periods of time. Methoxamine, the alpha1-agonist (tested only at the plateau period), had similar effects. In contrast, the alpha2-agonist, clonidine, deteriorated walking. Serotoninergic drugs, such as the neurotransmitter itself, serotonin (5HT), the precursor 5-hydroxytryptophan (5HTP), and the agonist quipazine improved the locomotion by increasing regularity of the hindlimb stepping and by increasing the step cycle duration. In contrast, the 5HT1A agonist 8-hydroxy-dipropylaminotetralin (DPAT) caused foot drag in one of the cats, resulting in frequent stumbling. Injection of combination of methoxamine and quipazine resulted in maintained, regular stepping with smooth movements and good lateral stability. Our results show that the effects of drugs can be integrated to the residual voluntary locomotion and improve some of its postural aspects. However, this work shows clearly that the effects of drugs (such as clonidine) may depend on whether or not the spinal lesion is complete. In a clinical context, this may suggest that different classes of drugs could be used in patients with different types of spinal cord injuries. Possible mechanisms underlying the effect of noradrenergic and serotoninergic drugs on the locomotion after partial spinal lesions are discussed.

5-Hydroxytryptophan↗

Interactions between posture and locomotion: motor patterns in humans walking with bent posture versus erect posture.

Human erect locomotion is unique among living primates. Evolution selected specific biomechanical features that make human locomotion mechanically efficient. These features are matched by the motor patterns generated in the CNS. What happens when humans walk with bent postures? Are normal motor patterns of erect locomotion maintained or completely reorganized? Five healthy volunteers walked straight and forward at different speeds in three different postures (regular, knee-flexed, and knee- and trunk-flexed) while their motion, ground reaction forces, and electromyographic (EMG) activity were recorded. The three postures imply large differences in the position of the center of body mass relative to the body segments. The elevation angles of the trunk, pelvis, and lower limb segments relative to the vertical in the sagittal plane, the ground reaction forces and the rectified EMGs were analyzed over the gait cycle. The waveforms of the elevation angles along the gait cycle remained essentially unchanged irrespective of the adopted postures. The first two harmonics of these kinematic waveforms explain >95% of their variance. The phase shift but not the amplitude ratio between the first harmonic of the elevation angle waveforms of adjacent pairs was affected systematically by changes in posture. Thigh, shank, and foot angles covaried close to a plane in all conditions, but the plane orientation was systematically different in bent versus erect locomotion. This was explained by the changes in the temporal coupling among the three segments. For walking speeds >1 m s(-1), the plane orientation of bent locomotion indicates a much lower mechanical efficiency relative to erect locomotion. Ground reaction forces differed prominently in bent versus erect posture displaying characteristics intermediate between those typical of walking and those of running. Mean EMG activity was greater in bent postures for all recorded muscles independent of the functional role. The waveforms of the muscle activities and muscle synergies also were affected by the adopted posture. We conclude that maintaining bent postures does not interfere either with the generation of segmental kinematic waveforms or with the planar constraint of intersegmental covariation. These characteristics are maintained at the expense of adjustments in kinetic parameters, muscle synergies and the temporal coupling among the oscillating body segments. We argue that an integrated control of gait and posture is made possible because these two motor functions share some common principles of spatial organization.

Adult↗

Locomotion and posture in Lagothrix lagotricha.

This long-term study of woolly monkey (Lagothrix) locomotor and postural behaviour employs methods identical to those used during a previous study of the locomotion and posture of two species of Ateles, allowing a detailed comparison between the two genera, which are strong competitors in extensive parts of the Amazon basin and northern Andes. As in Ateles, Lagothrix locomotion can be divided into five patterns, based on limb usage: quadrupedal walking and running, suspensory locomotion, climbing, bipedalism (very rare in wild woolly monkeys) and leaping. Lagothrix differs from Ateles primarily in its greater reliance on quadrupedal locomotion during both travel and feeding and on its de-emphasis of the use of suspensory locomotion as compared to Ateles, while the use of climbing and leaping is roughly equal in the two genera. Lagothrix exhibits more generalised (primitive) locomotive behaviour in accordance with its morphology, in comparison to the more specialised Ateles. The generic differences reflect differences in habitat use and particularly foraging ecology.

Animals↗

Locomotion and posture in Ateles geoffroyi and Ateles paniscus.

The locomotor and postural behavior of Ateles geoffroyi and Ateles paniscus was studied in Panama and Surinam. Ateles locomotion can be divided into five patterns on the basis of limb usage: quadrupedal walking and running, suspensory locomotion, climbing, bipedalism and leaping. The first three are commonly used in both locomotion during travel and locomotion during feeding, but climbing (especially 'horizontal climbing') is the most important pattern during feeding. Most Ateles locomotion takes place on twigs and branches, with twigs playing a greater role in feeding than in travel. Feeding postures are mainly suspensory and seated, short resting postures are suspensory, seated and standing, and long resting postures are almost entirely seated and reclining. Twigs are the most important supports in feeding postures, but branches are much more important in resting postures. The results of this study indicate that the quadrumanous climbing, forelimb-dominated locomotion during feeding that FLEAGLE considers the primary hominoid adaptation is also characteristic of Ateles.

Animals↗

Mechanical power and work of cat soleus, gastrocnemius and plantaris muscles during locomotion: possible functional significance of muscle design and force patterns.

Electrical activity, forces, power and work of the soleus (SO), the gastrocnemius (GA) and the plantaris (PL) muscles were measured during locomotion in the cat in order to study the functional role of these ankle extensor muscles. Forces and electrical activity (EMG) of the three muscles were measured using home-made force transducers and bipolar, indwelling wire electrodes, respectively, for walking and trotting at speeds of 0.4 to 1.8 m s-1 on a motor-driven treadmill. Video records and a geometrical model of the cat hindlimb were used for calculating the rates of change in lengths of the SO, GA and PL muscles. The instantaneous maximum possible force that can be produced by a muscle at a given fibre length and the rate of change in fibre length (termed contractile abilities) were estimated for each muscle throughout the step cycle. Fibre lengths of the SO, GA and PL were calculated using a planar, geometrical muscle model, measured muscle forces and kinematics, and morphological measurements from the animal after it had been killed. Mechanical power and work of SO, GA and PL were calculated for 144 step cycles. The contribution of the positive work done by the ankle extensor muscles of one hindlimb to the increase of the total mechanical energy of the body (estimated from values in the literature) increased from 4-11% at speeds of locomotion of 0.4 and 0.8 m s-1 to 7-16% at speeds of 1.2 m s-1 and above. The relative contributions of the negative and positive work to the total negative and positive work done by the three ankle extensor muscles increased for GA, decreased for SO and remained about the same for PL, with increasing speeds of locomotion. At speeds of 0.4-0.8 m s-1, the positive work normalized to muscle mass was 7.5-11.0 J kg-1, 1.9-3.0 J kg-1 and 5.3-8.4 J kg-1 for SO, GA and PL, respectively. At speeds of 1.2-1.8 m s-1, the corresponding values were 9.8-16.7 J kg-1, 6.0-10.7 J kg-1 and 13.4-25.0 J kg-1. Peak forces of GA and PL increased and peak forces of SO did not change substantially with increasing speeds of locomotion. The time of decrease of force and the time of decrease of power after peak values had been achieved were much shorter for SO than the corresponding times for GA and PL at fast speeds of locomotion. The faster decrease in the force and power of SO compared with GA and PL was caused by the fast decrease of the contractile abilities and the activation of SO. The results of this study suggest that the ankle extensor muscles play a significant role in the generation of mechanical energy for locomotion.

Animals↗

Mechanics of locomotion in lizards.

Lizards bend their trunks laterally with each step of locomotion and, as a result, their locomotion appears to be fundamentally different from mammalian locomotion. The goal of the present study was to determine whether lizards use the same two basic gaits as other legged animals or whether they use a mechanically unique gait due to lateral trunk bending. Force platform and kinematic measurements revealed that two species of lizards, Coleonyx variegatus and Eumeces skiltonianus, used two basic gaits similar to mammalian walking and trotting gaits. In both gaits, the kinetic energy fluctuations due to lateral movements of the center of mass were less than 5% of the total external mechanical energy fluctuations. In the walking gait, both species vaulted over their stance limbs like inverted pendulums. The fluctuations in kinetic energy and gravitational potential energy of the center of mass were approximately 180 degrees out of phase. The lizards conserved as much as 51% of the external mechanical energy required for locomotion by the inverted pendulum mechanism. Both species also used a bouncing gait, similar to mammalian trotting, in which the fluctuations in kinetic energy and gravitational potential energy of the center of mass were nearly exactly in phase. The mass-specific external mechanical work required to travel 1 m (1.5 J kg-1) was similar to that for other legged animals. Thus, in spite of marked lateral bending of the trunk, the mechanics of lizard locomotion is similar to the mechanics of locomotion in other legged animals.

Animals↗

The effect of selective brainstem or spinal cord lesions on treadmill locomotion evoked by stimulation of the mesencephalic or pontomedullary locomotor regions.

The descending pathways from the brainstem locomotor areas were investigated by utilizing reversible cooling (to block synaptic or fiber transmission) and irreversible subtotal lesions of the brainstem or spinal cord (C2-C3 level). Experiments were conducted on decerebrate cats induced to walk on a treadmill by electrical stimulation of the brainstem. Locomotion produced by stimulation of the mesencephalic locomotor region (MLR) was not abolished by caudal brainstem lesions that isolated the lateral tegmentum or by extended rostral/caudal dorsal hemisections of the spinal cord. These results demonstrate that the MLR does not require a pathway projecting through the lateral tegmentum of the brainstem or the dorsal half of the spinal cord, as previously suggested (Mori et al., 1977, 1978b; Shik and Yagodnitsyn, 1978; Shik, 1983). Rather, the results indicate that the descending pathway originating from the MLR projects through the medial reticular formation (MedRF) and the ventral half of the spinal cord. Locomotion produced by stimulation of the pontomedullary locomotor region (PLR) was blocked by reversible cooling of either the MedRF or the ventrolateral funiculus of the spinal cord. In some cases, locomotion could be produced by stimulation of the PLR following extended dorsal hemisections of the spinal cord. These results demonstrate that the PLR can also produce locomotion by activation of cells in the MedRF that project caudally through the ventral half of the spinal cord. Stimulation of the PLR could also elicit locomotion following its surgical isolation from the MedRF of the brainstem. Furthermore, lesions of the dorsal spinal cord resulted in the loss of PLR-evoked locomotion in some, but not all, cases. Thus, an alternative projection of the PLR through the dorsal half of the spinal cord (Kazennikov et al., 1980, 1983a,b; Shik, 1983) cannot be ruled out. Overall, these results demonstrate that the PLR is not an essential component of the motor pathway originating from the MLR. The organizational scheme of "brainstem locomotor regions" is discussed in the context of recent information demonstrating a link between the sensory component of the trigeminal system and locomotor pathways (Noga et al., 1988).

Animals↗

Locomotion evoked by stimulation of the brain stem in the Atlantic stingray, Dasyatis sabina.

The primary pathway descending to the spinal cord to initiate locomotion in the stingray is located in the intermediate to ventral portion of the lateral funiculus; a second pathway is located in the dorsolateral funiculus. The goal of this study was to identify the origins of these pathways in the rhombencephalic reticular formation (RF). To do this we used microstimulation of the RF in conjunction with selective lesions of the brain stem and spinal cord. In some animals microinjections of excitatory amino acids were used to avoid stimulating axons of passage. Locomotion in the contralateral pectoral fin was evoked by microstimulation of the dorsal and ventral reticular nuclei, the middle and superior RF, and the ventral portion of the lateral RF. The regions from which locomotion was evoked by chemical stimulation were more restricted and included the rostral dorsal reticular nucleus, the middle RF, and the adjacent ventral lateral RF. This area encompasses the magnocellular RF and coincides with the distribution of numerous reticulospinal cells that project ipsilaterally into the ventral half of the lateral funiculus. Our results indicate, then, that locomotion in the stingray is mediated primarily by a pathway originating in the magnocellular RF that descends ipsilaterally in the ventral half of the lateral funiculus to elicit swimming in the contralateral pectoral fin. We suggest that this primary pathway is specifically associated with the control of locomotion. We also demonstrated that locomotion can be evoked independently from the lateral RF, but is probably mediated by an indirect pathway relaying near the spinomedullary junction or in the rostral spinal cord.

Animals↗

Speed control in quadrupedal locomotion: principles of limb coordination in the dog.

Long distance, overground locomotion in the dog was observed and analyzed using the two dimensional gait diagram method. Though the velocity of locomotion chosen by the animals over a 1,000 m course varied, a preferred speed generally emerged and was used during most of the experiment. This animal-specific preferred overground velocity was strongly correlated with the animal's limb lengths, and corresponded to the minimum observed swinging velocity of the limbs. Changes in the pattern of limb coordination during three-limb locomotion were also investigated. Depending upon which limb was restrained, dogs used trot-like or gallop-like gaits which exhibited the same temporal and spatial phase differences as were observed during normal locomotion. However, stride length and swing-stance durations were increased relative to those observed in four legged locomotion. Animals with an additional 2 kg weight trotted slowly, but no significant changes in limb movement parameters were found. Locomotion studies performed in darkness resulted in an immediate switch from asymmetrical (galloping) to symmetrical gaits (walking and trotting). These gaits allow for precise foot placement.

Animals↗

Validity of power output estimation for wheelchair locomotion.

The purpose of this study was to validate an in-field method of estimating power output (PO) requirements for manual wheelchair (WC) locomotion. PO was calculated from the average force required to push a WC and its occupant over level tile and low pile carpeted surfaces multiplied by the locomotive velocity (3 km.hr-1). Average pushing force was determined by a strain-gauge transducer and an electronic integrator. Ten male volunteers (wt in WC = 73 -96 kg) were found to require PO levels ranging from 38 to 63 kpm.h4-1 and 98 to 135 kpm.min-1 for WC locomotion on the tiled and carpeted surface, respectively. Subjects then propelled the WC over the test surfaces at 3 km.h4-1 while steady state VO2, VE and HR were monitored. These variables were also monitored while the subjects operated a wheelchair ergometer (WERG) at corresponding PO levels. VO2 and VE were found to be about 15% higher, and HR about 3% higher for actual WC locomotion. High correlations were found for these variables between WC and WERG operation. Somewhat higher response values for WC locomotion may in part be due to the additional load of steering, inertial forces and weight of the gas collection apparatus. The similarity of these responses for both modes of exercise, however, suggests the validity of this method of determining PO requirements for WC locomotion.

Adult↗

Application of the dual-micropipet technique to the measurement of tumor cell locomotion.

The objective of this work was to characterize tumor cell locomotion in response to chemotactic stimulation using a dual-micropipet assay. The assay involves two micropipets. An individual A2058 human melanoma cell was retained, without pressure gradient, in a pipet of approximately 14 micrometers i.d. A solution of type IV collagen, chosen as the chemotactic source, was placed in another pipet (approximately 10 micrometers o.d.) with zero pressure at the pipet tip. The smaller pipet was then inserted into the larger one containing the melanoma cell. The initial chemoattractant concentration (C0) and the distance between the tip of the small pipet and the cell surface (delta) provided a gradient (C0/delta) for tumor cell locomotion toward stimulation. This novel assay provides a direct measure of cell movement: cyclic pseudopod protrusion (Lp) and subsequent cell locomotion (Lc). The influences of different adhesion substrates on cell locomotion were also studied. The peak length in Lp precedes the highest locomotion velocity (dLc/dt) by an apparent lag time. C0/delta influences pseudopod protrusion frequency (fp) and dLc/dt, but not significantly on Lp. Substrate adhesions affect dLc/dt, but apparently not Lp or fp. In conclusion, pseudopod protrusion and substrate adhesion are two necessary but mutually independent factors in tumor cell locomotion. dLc/dt correlates with changes in C0/delta, which is in significant correlation with fp but not Lp.

Chemotaxis↗

Adaptational and learning processes during human split-belt locomotion: interaction between central mechanisms and afferent input.

Split-belt locomotion (i.e., walking with unequal leg speeds) requires a rapid adaptation of biomechanical parameters and therefore of leg muscle electromyographic (EMG) activity. This adaptational process during the first strides of asymmetric gait as well as learning effects induced by repetition were studied in 11 healthy volunteers. Subjects were switched from slow (0.5 m/s) symmetric gait to split-belt locomotion with speeds of 0.5 m/s and 1.5 m/s, respectively. All subjects were observed to adapt in a similar way: (1) during the first trial, adaptation required about 12-15 strides. This was achieved by an increase in stride cycle duration, i.e., an increase in swing duration on the fast side and an increase in support duration on the slow side. (2) Adaptation of leg extensor and flexor EMG activity paralleled the changes of biomechanical parameters. During the first strides, muscle activity was enhanced with no increase in coactivity of antagonistic leg muscles. (3) A motor learning effect was seen when the same paradigm was repeated a few minutes later--interrupted by symmetric locomotion--as adaptation to the split-belt speeds was achieved within 1-3 strides. (4) This short-time learning effect did not occur in the "mirror" condition when the slow and fast sides were inverted. In this case adaptation again required 12-15 strides. A close link between central and proprioceptive mechanisms of interlimb coordination is suggested to underlie the adaptational processes during split-belt conditions. It can be assumed that, as in quadrupedal locomotion of the cat, human bipedal locomotion involves separate locomotor generators to provide the flexibility demanded. The present results suggest that side-specific proprioceptive information regarding the dynamics of the movement is necessary to adjust the centrally generated locomotor activity for both legs to the actual needs for controlled locomotion. Although the required pattern is quickly learned, this learning effect cannot be transferred to the contralateral side.

Adaptation, Physiological↗

The responses of cat motor cortical units to electrical cutaneous stimulation during locomotion and during lifting, falling and landing.

Experiments were performed to examine the influence of cutaneous information on motor cortical cells during movement in intact, awake cats. The movements investigated were locomotion and a sequence in which the animal was repeatedly lifted and dropped. Electrical stimuli to distal skin areas were delivered periodically during the movements and responses of motor cortical cells were examined. The animals used in these experiments were chronically implanted with cortical microelectrodes, a pyramidal tract stimulating electrode, cutaneous stimulating electrodes in the forepaw, and a recording cuff electrode around the median nerve. EMG electrodes were implanted in several forelimb muscles and a length gauge was implanted across the elbow joint. Results included in this report were obtained from three cats. The twenty-two cortical units analysed in this study (seven were PT units) were selected from a larger sample by the following criteria: cutaneous receptive fields which included the distal part of the limb, consistent short latency responses to electrical cutaneous stimulation and spontaneous activity modulated in consistent patterns during the movement investigated. Sixteen units were recorded during locomotion, 12 during the lifting and dropping cycle and 6 of these during both conditions. Most of the cells were influenced by the cutaneous input during locomotion. Three units had no response to peripheral stimulation during locomotion though they were responsive to this stimulus when the animal was sitting quietly. All the cells were responsive to the cutaneous input during the lifting and dropping cycle. The responses to cutaneous stimuli were found to be modulated in relation to phases of the step cycle and the lifting and dropping cycle. In 13 units this modulation did not parallel the modulation of the unit's spontaneous firing during these activities. For these units a common finding during locomotion was that the response to cutaneous stimuli increased throughout stance, reached maximum during the flexion part of the swing, and then declined to a minimum during the beginning of the next stance. During the lifting and dropping cycle, the responses were greatest when the animal was held in the air and when starting to fall, and minimal just prior to and after landing. In both movements, cutaneous responses were reduced when the limb was used to support the animal's weight. There is apparently a movement phase-related modulation of cutaneous input to some motor cortical cells. This modulation of cutaneous input resembled the modulation of cutaneous reflexes during locomotion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Interactions of Ro15-4513, Ro15-1788 (flumazenil) and ethanol on measures of exploration and locomotion in rats.

The present study investigated the role of the GABAA-benzodiazepine (BDZ) receptor complex in mediating ethanol (ETOH)-induced increases in exploration (head-dipping) and locomotion of rats in a holeboard test. Male Sprague-Dawley rats were selected based on low basal exploratory rates to increase the likelihood that ETOH would increase these behaviors. The effects of the BDZ partial inverse agonist, Ro15-4513 (2.5 mg/kg), and the BDZ receptor antagonist, Ro15-1788 (flumazenil) (8.0 mg/kg), alone, and in combination with ETOH (0.25, 0.50 and 0.75 g/kg, IP) were investigated. The 0.25 and 0.50 g/kg doses of ETOH markedly increased both exploration and locomotion in low exploratory rats. The ETOH-induced increases were prevented by Ro15-4513 on both measures at a dose that produced no observable intrinsic action; however, this apparent lack of intrinsic activity on exploration may have been related to the low basal rates of responding in the subjects. The BDZ antagonist, flumazenil, completely reversed the antagonistic action produced by Ro15-4513 of the ETOH-induced stimulant effects on locomotion, however, flumazenil exerted only a marginal statistically significant effect on Ro15-4513's actions on head-dipping. When flumazenil was given alone, it increased head-dipping, but was without effect on locomotion. Flumazenil did not affect ETOH-induced increases in locomotion; however, ETOH and flumazenil appeared to show agonistic effects on exploration. The different effects exerted by flumazenil alone, and in combination with ETOH on head-dipping and locomotion suggest that the actions of flumazenil on these behaviors are mediated through separate mechanisms. The research further suggests that both the anxiolytic and locomotor activational effects of ETOH are mediated through the GABAA-BDZ receptor complex.

Animals↗

Maintenance of amphetamine-induced stereotypy and locomotion requires ongoing dopamine receptor activation.

Amphetamine-induced locomotion and stereotypy depend on dopamine (DA), yet, while extracellular DA concentrations peak early, and then begin to decline, intense stereotyped behaviors continue for relatively prolonged periods. These observations suggest that DA may act as a "trigger" for the entire multiphasic behavioral response. To test this hypothesis in rats, haloperidol (HAL) was injected at different times with respect to (AMPH), and automated and videotaped measures of the behavior were recorded. HAL (0.1 mg/kg, i.p.) or saline was administered either 15 min prior to AMPH (4.0 mg/kg, s.c.); 60 min following AMPH (during the phase of intense oral stereotypy); or 140 min after AMPH (during post-stereotypy locomotion). When administered prior to AMPH, HAL prevented the development of stereotypy, and an increase in locomotion was displayed in place of stereotypy. Haloperidol administration during stereotypy interrupted the response, and resulted in an increase in locomotion for the remainder of the stereotypy phase. In neither of these cases did HAL affect post-stereotypy locomotion. However, when injected during the post-stereotypy phase, HAL caused a decrease in the magnitude of the locomotor response, suggesting that both the stereotypy and locomotor components of the response remain sensitive to HAL at times when DA levels have significantly declined. These results do not support the hypothesis that the early increase in extracellular DA produced by AMPH, acts as a "trigger" for a non-dopaminergic receptor mediated expression of the later phases of the AMPH response. Instead, it appears that both stereotypy and post-stereotypy locomotion remain sensitive to DA receptor blockade when extracellular DA levels are below the levels produced by non-stereotypy-inducing doses of AMPH.

Animals↗

Unbiased cocaine conditioned place preferences (CPP) obscures conditioned locomotion, and nimodipine blockade of cocaine CPP is due to conditioned place aversions.

The effect of nimodipine (0, 0.1, 1.0 and 10 mg/kg, SC), a dihydropyridine L-type Ca2+ channel antagonist, on the establishment of cocaine-(10 mg/kg IP) conditioned place preferences (CPP) was investigated. Nimodipine produced conditioned place aversions (CPA) on its own; reductions in cocaine CPP are apparently due to this CPA. There is a high negative correlation between time spent in the CS+ compartment and the difference in locomotion rates between the CS+ and the non-drug (CS-) compartments, independent of drug effects. This relationship is responsible for an increased rate of locomotion observed in the CS- compartment in cocaine-conditioned rats. Analysis of covariance indicated that cocaine CPP occurred independently of cocaine's effects on locomotion. Furthermore, cocaine produces an increase in the rate of locomotion in the CS+ compartment when time spent in this compartment is equated with time spent in the CS- compartment. This suggests that cocaine's effects on CPP and "conditioned" locomotion are due to separate mechanisms of action. On the other hand, nimodipine-induced place aversions and locomotor rates are not independent of each other, indicating a common mechanism of action, or that one is a consequence of the other. It is concluded that place preferences and place aversions can sometimes be secondary to compartment-specific locomotor changes, and locomotion effects can be confounded by differential times spent in each compartment. The relationships between these two behaviours must be controlled for before conclusions of CPP or CPA can be drawn in drug conditioning studies.

Animals↗