Biomedical subjects

C Van Hartesveldt

Publications and source records attributed to C Van Hartesveldt.

At least 19 recordsLinked to original sources

PubMed2000

Kinematic analyses of air-stepping in normal and decerebrate preweanling rats.

We studied the ability of L-DOPA (100 mg/kg, subcutaneous) to elicit air-stepping in decerebrate and sham-operated Sprague-Dawley rats from postnatal Day 5 through postnatal Day 20. The most common gait consisted of fore- and hindlimb alternation, but between 10 and 20 days of age, patterns of coordination resembling swimming, in which the forelimbs remained adducted, and galloping became more frequent in both decerebrate and sham-operated rats. Because episodes of galloping were rarely more than two or three step cycles in length, our analyses focused on episodes of stepping in which limbs within the girdles stepped in alternation and diagonal pairs of limbs moved in synchrony ("trot"). The rate of stepping of both decerebrate and sham-operated rats increased from about 2.9 steps/s at Day 5 to about 4 steps/s at Day 20. In both groups, this increase was found to result from a decrease in the duration of the retraction phase of the step cycle. Amplitudes of movement at the wrist, knee, and ankle increased with age in both decerebrate and sham-operated neonates, whereas those of the shoulder, elbow, and hip did not change in either group. The timing of movements at joints within each limb also changed similarly with age in sham-operated and decerebrate pups. During development, forelimb movement was increasingly led by the wrist, which was followed by the elbow and then finally by the shoulder. Hindlimb movements were increasingly led by the knee, followed by the ankle, and finally by the hip. At all ages, diagonal limbs moved in synchrony, and heterolateral limbs within each girdle moved in antiphase. However, the phase relationship between hindlimb and forelimb movements changed both in sham-operated rats and in decerebrate rats during ontogeny. On Day 5, movement of each hindlimb was phase-delayed relative to that of the diagonal forelimb whereas on Days 15 and 20, the hindlimb was phase-advanced. The parallel emergence of different gaits and the similarity of coordination during diagonal progression in sham-operated and decerebrate pups show that age-related changes in gait are mediated no more rostrally than the midbrain.

Age Factors↗

PubMed1999

The NMDA antagonist, MK-801, alters L-DOPA-induced air-stepping in neonatal rats.

Administration of L-DOPA (sc) to neonatal rats suspended in harnesses induces coordinated stepping of all four limbs (diagonal progression; L-DOPA-induced air-stepping) by 5 days of age. Because NMDA also induces locomotion in several species, NMDA receptor activation may be required for L-DOPA to elicit coordinated air-stepping. The purpose of the present experiment was to determine if the NMDA receptor antagonist, MK-801, would block L-DOPA-induced air-stepping in developing rats. Neonatal rats administered MK-801 alone rarely air-stepped with the forelimbs or hindlimbs in a coordinated fashion, whereas those treated with L-DOPA alone primarily stepped with all four limbs using a diagonal progression pattern during the session. In contrast, the number of limbs that stepped during the session was gradually altered in 5- to 20-day-old rats treated with MK-801 + L-DOPA. Gaits of those rats progressed from diagonal progression to extension of the forelimbs beneath the chin with hindlimb alternation, to forelimb extension without hindlimb activity. Twenty-day-olds treated with MK-801 + L-DOPA subsequently became completely inactive when the forelimbs dropped from their elevated position beneath the chin. In addition to the sequence just described, 15-day-old rats treated with the lowest concentration of MK-801 + L-DOPA occasionally stepped with one pair of homolateral limbs or stepped with the hindlimbs in near synchrony while the forelimbs either stepped in alternation, were extended beneath the chin or groomed the face. Because limb participation during L-DOPA-induced air-stepping was altered in neonatal rats pretreated with MK-801, NMDA receptor activation may be important for locomotor coordination (gait).

Animals↗

PubMed1999

Locomotion elicited by MK801 in developing and adult rats: temporal, environmental, and gender effects.

The effects of environmental novelty on locomotion elicited by an N-methyl-D-aspartate (NMDA) receptor antagonist, (+)MK-801 hydrogen maleate [(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine], were investigated. Male and female rats aged 10, 20, 30 or 54-68 days were injected s.c. with MK801 and placed in activity monitors either immediately (no-delay) or after a 60 min delay (delay). In the no-delay condition, MK801 induced an inverse U-shaped dose-response effect on locomotion; peak activation occurred with 0.1 mg/kg and ataxia occurred with higher doses. The introduction of a novel environment 60 min after drug injection shifted the dose-effect function of MK801 to the left; i.e., in rats 20 days of age and older, the activity induced by 0.1 mg/kg MK801 was potentiated in the delay condition. For the 0.5 mg/kg dose, 20-day-olds showed activation in the no-delay condition but ataxia in the delay condition. This dose induced ataxia followed by activation in 30-day-olds and adult males or ataxia in adult females, regardless of delay condition. Age-, gender-, and novelty-dependent variations in MK801-induced locomotion may reflect differences in limbic-motor circuitry.

Age Factors↗

PubMed1999

The locomotor effects of MK801 in the nucleus accumbens of developing and adult rats.

This developmental study was an investigation of locomotion induced by the NMDA receptor antagonist, (+)MK-801 hydrogen maleate [(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine], at doses of 0, 3 or 10 microg injected bilaterally into the nucleus accumbens of rats at 11, 21, 31, or 61-66 days of age. During a 2-h test session, only a few 11-day-old pups responded to either dose of MK801; they displayed short bouts of obstinate progression. In contrast, 21- and 31-day-olds were not affected by 3 microg MK801 but exhibited robust activation after 10 microg MK801. The activation was greatest in 21-day-olds and also occurred after mid-striatal injections in 21- but not 31-day-old rats. Adult rats injected with MK801 were not robustly activated, but they maintained their initial level of activity throughout the test session, instead of habituating to the test monitor, as controls did. Ontological changes in MK801-induced activity are likely to reflect maturation of glutamate transmission in the nucleus accumbens.

Animals↗

PubMed1999

The locomotor effects of quinpirole in rats depend on age and gender.

Periadolescence in the rat [postnatal day (PND) 35-50] is an important but understudied period of neurobehavioral development. In this experiment, an ongoing survey of the effects of quinpirole in developing rats was completed by the addition of periadolescent rats to the range of ages tested. PND40 or 50 rats were injected subcutaneously with the dopamine D2/D3 receptor agonist, quinpirole (0.0, 0.02, 0.2, or 2.0 mg/kg), and their locomotor activity was recorded. Periadolescent rats showed adult-like locomotor responses to either the 0.2 or 2.0 mg/kg doses of quinpirole, i.e., the responses were biphasic with respect to time: early suppression of locomotion followed by later activation within a single test session. In younger female rats (PND40) but older male rats (PND50), the lowest dose of quinpirole suppressed activity early in the test session but did not increase it later. In male rats, the magnitude of locomotor activation declined with age. Taken together with previous data from this laboratory, these results suggest that periadolescent rats exhibit locomotor responses that fall along a continuum from a high level of activation just after weaning to a low level of activation in early adulthood.

Age Factors↗

PubMed1997

Effects of the putative dopamine D3 receptor antagonist PNU 99194A on motor behavior and emotional reactivity in C57BL/6J mice.

Due to the regional expression of D3 dopamine receptors in limbic areas of the brain, there has been considerable interest in the potential role of this receptor subtype in mediating emotional behavior. Previous studies in habituated rats have shown that the putative dopamine D3 receptor antagonist 5,6-dimethoxy-2-(di-n-propylamino)indan (PNU 99194A) increased locomotor behavior. The present study examined the effects PNU 99194A on motor and emotional behaviors in C57BL/6J mice. Motor behavior was assessed in both habituated and nonhabituated mice. Emotional behavior was assessed using the elevated plus-maze and a social context involving an isolated C57BL/6J mouse and a nonaggressive conspecific. In mice habituated to the activity chamber prior to drug administration, PNU 99194A increased locomotion and rearing at lower doses (5, 10 mg/kg) whereas higher doses (20, 30 mg/kg) reduced these behaviors early in the test session. Thigmotaxis was increased independently of the effects on motor behavior. In mice exposed to the activity chamber for the first time, PNU 99194A produced a weak motor activation at lower doses and an initial decrease in motor behavior at higher doses that was followed by an increase in locomotion later in the test session. PNU 99194A had no systematic effects on activity in the elevated plus-maze, but dose-dependently increased flight reactivity in the social reactivity paradigm. These and previous findings raise questions about the role of dopamine D3 receptors in mediating motor behavior and emotional reactivity as well as the pharmacology of this putative dopamine D3 receptor antagonist.

Animals↗

PubMed1997

Dopamine D1 and D2 antagonists block L-DOPA-induced air-stepping in decerebrate neonatal rats.

L-DOPA administered to neonatal rats suspended in air elicits stereotypic locomotor activation termed air-stepping; it can be dose-dependently blocked by a dopamine (DA) D1 or D2 antagonist. In order to determine whether the forebrain is the site for this blockade, decerebrate 5-day-old rats were pretreated subcutaneously with either the DA D1 receptor antagonist SCH 23390 (16 mg/kg), the DA D2 receptor antagonist spiperone (6 mg/kg), or vehicle before receiving 100 mg/kg L-DOPA. Both antagonists blocked L-DOPA-induced air-stepping in both decerebrate and intact pups.

Animals↗

PubMed1997

A kinematic comparison of L-DOPA-induced air-stepping and swimming in developing rats.

In Experiment 1, rats of 5, 10, 15, and 20 days of age were injected with L-DOPA to elicit stepping and videotaped while suspended in air and in warm water. Inter- and intralimb coordination were similar for L-DOPA-induced air-stepping and swimming at all ages. Other parameters of locomotion, such as step length and step rate, varied by substrate. In Experiment 2, pups of 5 to 20 days of age received an injection of L-DOPA or the vehicle and were videotaped while freely swimming. L-DOPA-induced free swimming was more stereotyped and "automatonlike" than that of vehicle-injected animals. Through 15 days of age, all pups swam using all four limbs, but L-DOPA induced stricter synchrony of movement in diagonal limbs than was used by pups injected with the vehicle. At postnatal Day 20, vehicle-injected pups adopted the adult swimming pattern in which only the hindlimbs were used, whereas L-DOPA-injected pups continued to use the immature pattern, diagonal progression with all four limbs. These results suggest that L-DOPA-induced air-stepping and swimming are manifestations of the same central mechanisms and that parameters of L-DOPA-induced stepping are modified by the sensory and/or biomechanical effects of the substrate. Although the free swimming of L-DOPA-injected pups was kinematically similar to vehicle-treated pups, L-DOPA retarded transition to the adult swimming pattern.

Aging↗

PubMed1997

Temporal and environmental effects on quinpirole-induced biphasic locomotion in rats.

The dopamine D2/D3 agonist quinpirole induces suppression of locomotor activity at low doses, and suppression followed by activation at high doses when given to rats of 30 days of age and older that are immediately placed in activity monitors. The duration of suppression is longer and the level of activation is lower at 60 than at 30 days of age, suggesting that the mechanism responsible for the suppression may play a role in the lesser activation in the older rats. However, habituation limits the ability to measure the duration of locomotor suppression. Therefore, 0, 0.2, or 0.2 mg/kg quinpirole was injected S.C. either 30, 60, or 120 min before placing male or female rats of 30 or 60 days of age in activity monitors for 30 min. At both ages, both doses of quinpirole suppressed activity when the animal was placed in the monitor 30 or 60 min after injection; at 60 days the drug also suppressed activity at 120 min after injection. Previously, 0.2 mg/kg quinpirole elicited locomotor activity 60 min after injection in rats placed immediately in activity monitors at both ages. Thus, not only time after injection but novelty of the environment are critical factors in the expression of locomotor suppression or activation in response to quinpirole.

Animals↗

PubMed1997

L-DOPA and quipazine elicit air-stepping in neonatal rats with spinal cord transections.

Acute mid-thoracic spinal cord transection eliminates hindlimb air-stepping in neonatal rats suspended in harnesses and administered L-DOPA. Because spinal cord transection eliminates all descending inputs to the hindlimb locomotor circuits, this experiment determined if coadministration of L-DOPA and quipazine (serotonin receptor agonist) would induce hindlimb air-stepping in rat pups 24 hr after transection. Hindlimb steps of spinally transected pups that received L-DOPA or quipazine alone were infrequent and slow; hindlimb steps induced by L-DOPA + quipazine occurred more frequently and were faster than those elicited by either drug alone. These findings suggest that catecholaminergic and serotonergic systems both contribute to hindlimb stepping.

Animals↗

PubMed1996

The locomotor effects of a putative dopamine D3 receptor agonist in developing rats.

Dopamine receptors have been categorized into subfamilies D1 and D2, each with separate roles in dopamine-mediated behaviors. Of the D2 subfamily, the dopamine D3 receptor has been cloned, but the behavioral effects of selectively stimulating the D3 receptor are largely unknown. The purpose of this study was to quantify the locomotor responses of developing rats to the putative dopamine D3 receptor agonist, 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT). One of three doses of 7-OH-DPAT (0.01, 0.10, 1.00 mg/kg) or saline was injected subcutaneously into rats at the age of 10,20,30, or 60 days. Five minutes after the injection, rats were placed in automated activity monitors which recorded locomotor behavior at 5 min intervals for 2 h. The high dose of 7-OH-DPAT increased locomotor activity in rats of all ages. The medium and low doses increased activity in 10- and 20-day-old rats but not in 30- or 60-day-old rats. The level of drug-induced activation peaked at 20 days of age. In 30- and 60-day-old rats, but not 10- and 20-day-old rats, a period of locomotor suppression preceded the activation in response to the high dose of 7-OH-DPAT. In rats aged 20 days and older, the middle and low doses decreased locomotion early in the test session, but activation did not ensue. This dose-response pattern across ontogeny closely resembles that induced by quinpirole, an agonist at the dopamine D2 receptor subfamily.

Age Factors↗

PubMed1995

Sulpiride antagonizes the biphasic locomotor effects of quinpirole in weanling rats.

Low doses of dopamine (DA) agonists such as the D2 receptor subfamily agonist quinpirole are thought to stimulate DA autoreceptors selectively, thereby inhibiting locomotor activity. High doses of quinpirole initially suppress and later activate locomotion during a single test-session; the activation is presumably due to stimulation of postsynaptic receptors. The aim of this study was to investigate whether pretreatment with a selective DA D2 receptor antagonist, sulpiride, could block the putative autoreceptor-mediated inhibition at a lower dose than was required to block the postsynaptically mediated activation. Male and female 30-day-old rats were injected SC with one of eight doses of sulpiride (0.313-40 mg/kg) or the vehicle. Sixty minutes later, rats were injected SC with 0.2 mg/kg quinpirole or the vehicle. Five minutes after the second injection, rats were placed in automated activity monitors which recorded locomotor behavior for 60 min at 5-min intervals. Quinpirole at this dose first suppressed and later increased locomotor activity. Sulpiride pretreatment dose-dependently reversed both the early inhibition and later activation of quinpirole-induced locomotion. However, sulpiride did not block the quinpirole-induced early suppression at a lower dose than was required to block the later activation. Thus, there was no evidence that the locomotor suppression elicited by quinpirole is mediated by a more sensitive subset of DA receptors.

Animals↗

PubMed1994

L-dopa-induced air-stepping in preweanling rats. I. Effects of dose and age.

The effects of several doses of L-DOPA (25, 50, 75 and 100 mg/kg) on air-stepping were studied in rats on the day of birth and on 5, 10, 15 and 20 days of age. Occurrence of air-stepping increased and latency to air-stepping generally decreased with dose except at 10 days of age; duration of air-stepping increased with increasing dose of L-DOPA at every age. The occurrence of a variety of air-stepping gaits was age-dependent. On the day of birth, air-stepping consisted primarily of episodes of forelimb alternation; on days 5-20, diagonal progression was the predominant gait, but beginning at day 10, episodes of air-swimming, air-galloping and other locomotor patterns were interspersed. Not only could the durations of most of these gaits be increased with increasing dose of L-DOPA, but at some ages, increasing the dose of L-DOPA led to gait changes.

Aging↗

PubMed1994

L-dopa-induced air-stepping in preweanling rats. II. Kinematic analyses.

Coordination of air-stepping elicited by subcutaneous injections of L-DOPA (25-100 mg/kg) was studied in rats from the day of birth through 20 days of age. Results revealed a nearly linear increase in the rate of stepping from about 1.5 steps/s at day 0 to about 4.5 steps/s at day 20, independent of the dose of L-DOPA. The ontogenetic increase in the rate of stepping was found to result from decreases in the duration of both retraction and protraction phases of the step cycle, but the decrease in the retraction phase was greater. There was an ontogenetic increase in the amplitude of movement at the wrist, knee and ankle joints, a slight decline in the amplitude of movement at the elbow and little change in amplitude at either the shoulder or hip. The relative timing of movements at joints within each limb also changed with age. Forelimb movements were led by the wrist throughout development, followed by the elbow and then the shoulder, which increasingly lagged behind the other two joints of the forelimb. Hindlimb movements were increasingly led by the knee, followed by the ankle and then the hip. Diagonal progression, in which the diagonal limbs moved in phase with each other and in antiphase with the contralateral limb of the same girdle, was seen at all ages. However, other gaits, which resembled galloping (air-galloping) and swimming (air-swimming), became more prevalent between 10 and 20 days of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1994

Noradrenergic alpha-1 and alpha-2 antagonists block L-dopa-induced air-stepping in neonatal rats.

Five-day-old rat pups suspended in air and administered L-3,4-dihydroxyphenylalanine (L-DOPA) engage in a highly stereotyped and coordinated locomotor behavior termed air-stepping. L-DOPA is a precursor for dopamine and noradrenaline and one or both of these neurotransmitters could play a role in L-DOPA-induced air-stepping. The role of noradrenaline was investigated by assessing the abilities of the alpha-1 noradrenergic receptor antagonist prazosin and the alpha-2 noradrenergic receptor antagonist idazoxan to block L-DOPA-induced air-stepping in 5-day-old rats. Both antagonists decreased the duration of air-stepping. In addition, prazosin altered the topography of air-stepping by interfering with coordination of the hindlimbs. The results suggest that alpha-1 and alpha-2 noradrenergic receptor subtypes are involved in L-DOPA-induced air-stepping.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1994

Ontogeny of biphasic locomotor effects of quinpirole.

The effects of the dopamine D2/D3 receptor agonist quinpirole (LY171555) on locomotor activity were tested on rats of 10, 15, 20, 30, and 60 days of age. In two separate experiments, doses of 0 (vehicle), 0.02, 0.2, or 2.0 mg/kg quinpirole were injected SC into rats at each age, and their effects measured either for 2 h at 15-min intervals, or 30 min at 5-min intervals. At 10, 15, and 20 days of age, quinpirole significantly increased distance travelled in a dose-dependent manner. At 30 and 60 days of age, quinpirole significantly decreased distance travelled early in the session and increased it later. These results suggest that a dopamine autoreceptor begins to function between 20 and 30 days of age. Concomitant with the appearance of quinpirole-induced locomotor suppression early in the session, the amount of quinpirole-induced activation late in the session declined.

Aging↗

PubMed1993

Differential effects of SCH 23390 on immobility behaviors in developing rats.

The effects of a single injection of a dopamine D1 antagonist, SCH 23390, at doses of 0, 0.05, 0.1, and 0.2 mg/kg on three different kinds of immobility behavior were tested in rats of 10, 15, 20, and 30 days of age. Each animal was tested for the dorsal immobility response (DIR), vertical cling catalepsy, and bar catalepsy. A different pattern of results was found for each of the three immobility behaviors. SCH 23390 significantly increased the DIR at each age except 15 days; there was a progressive increase in effect from 10 to 20 to 30 days of age. At the lowest dose, drug-induced bar catalepsy peaked at 15 days of age and declined at 20 and 30 days of age. The effect of SCH 23390 on vertical cling catalepsy increased with age, plateauing at 20 days. Thus, the developmental pattern of immobility responses to this dopamine D1 antagonist differs with each behavior measured.

Age Factors↗

PubMed1993

Locomotor activity following intra-accumbens microinjections of dopamine D1 agonist SK&F 38393 in rats.

The present study examined the effects of the dopamine D1 receptor subtypes agonist SK&F 38393 on locomotor activities after bilateral microinjection (0.00, 0.01, 0.1, 1.0, 10.0 micrograms) into the nucleus accumbens (Acb). The dose of 0.1 microgram elicited the highest response rate across measures of locomotion, rearing and stereotypy behavior. On the other hand, the largest dose of 10.0 micrograms was associated with significant increase in center time behaviors. The data were supportive of the hypothesis that dose-related locomotor activities elicited by microinjections of SK&F 38393 into the Acb are independently mediated by D1 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗