Dose dependence of the 5-HT agonist quipazine in facilitating spinal stepping in the rat with epidural stimulation

Ichiyama, Ronaldo M.; Gerasimenko, Yury; Jindrich, Devin L.; Zhong, Hui; Roy, Roland R.; Edgerton, V. Reggie

doi:10.1016/j.neulet.2008.04.080

Cited by 55 publications

(63 citation statements)

References 22 publications

(31 reference statements)

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“…We also showed that ES in combination with the administration (intraperitoneal) of the 5-HT agonist quipazine produces a greater number of coordinated plantar steps on a moving treadmill when compared with ES alone or quipazine alone (Gerasimenko et al, 2007;Ichiyama et al, 2008). In those studies, ES plus quipazine acutely changed the physiological state of the lumbosacral spinal cord in a manner that enabled coordinated locomotion to occur in response to proprioceptive input without input from the brain.…”

Section: Introductionmentioning

confidence: 71%

Step Training Reinforces Specific Spinal Locomotor Circuitry in Adult Spinal Rats

Ichiyama¹,

Courtine²,

Gerasimenko³

et al. 2008

J. Neurosci.

154

151

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Locomotor training improves function after a spinal cord injury both in experimental and clinical settings. The activity-dependent mechanisms underlying such improvement, however, are sparsely understood. Adult rats received a complete spinal cord transection (T9), and epidural stimulation (ES) electrodes were secured to the dura matter at L2. EMG electrodes were implanted bilaterally in selected muscles. Using a servo-controlled body weight support system for bipedal stepping, five rats were trained 7 d/week for 6 weeks (30 min/d) under quipazine (0.3 mg/kg) and ES (L2; 40 Hz). Nontrained rats were handled as trained rats but did not receive quipazine or ES. At the end of the experiment, a subset of rats was used for c-fos immunohistochemistry. Three trained and three nontrained rats stepped for 1 h (ES; no quipazine) and were returned to their cages for 1 h before intracardiac perfusion. All rats could step with ES and quipazine administration. The trained rats had higher and longer steps, narrower base of support at stance, and lower variability in EMG parameters than nontrained rats, and these properties approached that of noninjured controls. After 1 h of stepping, the number of FOSϩ neurons was significantly lower in trained than nontrained rats throughout the extent of the lumbosacral segments. These results suggest that training reinforces the efficacy of specific sensorimotor pathways, resulting in a more selective and stable network of neurons that controls locomotion.

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Section: Introductionmentioning

confidence: 71%

Step Training Reinforces Specific Spinal Locomotor Circuitry in Adult Spinal Rats

Ichiyama¹,

Courtine²,

Gerasimenko³

et al. 2008

J. Neurosci.

154

151

View full text Add to dashboard Cite

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“…Although these levels are not noticeable in the air-stepping paradigm, significant differences do emerge in a testing environment that introduces cutaneous sensory stimulation. Interestingly, Ichiyama and colleagues [33] found quipazine dose-dependent changes in coordination in adult spinal rats. Higher doses of quipazine resulted in a decrease in coordinated movement, as well as the number of plantar steps.…”

Section: Discussionmentioning

confidence: 99%

Serotonergic activation of locomotor behavior and posture in one-day old rats

Swann

Kempe

Orden

et al. 2016

Behavioural Brain Research

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The purpose of this study was to determine what dose of quipazine, a serotonergic agonist, facilitates air-stepping and induces postural control and patterns of locomotion in newborn rats. Subjects in both experiments were 1-day-old rat pups. In Experiment 1, pups were restrained and tested for air-stepping in a 35-min test session. Immediately following a 5-min baseline, pups were treated with quipazine (1.0, 3.0, or 10.0 mg/kg) or saline (vehicle control), administered intraperitoneally in a 50 microliter injection. Bilateral alternating stepping occurred most frequently following treatment with 10.0 mg/kg quipazine, however the percentage of alternating steps, interlimb phase, and step period were very similar between the 3.0 and 10.0 mg/kg doses. For interlimb phase, the forelimbs and hindlimbs maintained a near perfect anti-phase pattern of coordination, with step period averaging about 1 second. In Experiment 2, pups were treated with 3.0 or 10.0 mg/kg quipazine or saline, and then were placed on a surface (open field, unrestrained). Both doses of quipazine resulted in developmentally advanced postural control and locomotor patterns, including head elevation, postural stances, pivoting, crawling, and a few instances of quadrupedal walking. The 3.0 mg/kg dose of quipazine was the most effective at evoking sustained locomotion. Between the 2 experiments, behavior exhibited by the rat pup varied based on testing environment, emphasizing the role that environment and sensory cues exert over motor behavior. Overall, quipazine administered at a dose of 3.0 mg/kg was highly effective at promoting alternating limb coordination and inducing locomotor activity in both testing environments.

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“…The following challenges were used: (1) MK-801, a glutamatergic NMDA receptor antagonist, at doses of 0.1, 0.2 or 0.3 mg/kg (Bubenikova-Valesova et al 2007; Jacobs et al 2000; Su et al 2007); (2) SKF-82958, a DA D 1 receptor agonist, at doses of 0.1, 1.0 or 2.0 mg/kg (Maneuf et al 1997); (3) quinpirole, a DA D 2/3 receptor agonist, at doses of 0.5, 1.0 or 1.5 mg/kg (Stuchlik et al 2007); or (4) quipazine, a non-selective serotonin 5-HT 2/3 receptor agonist, was given of 0.1, 0.3 or 0.5 mg/kg (Antri et al 2005; Ichiyama et al 2008). All drugs were obtained from Sigma-Aldrich (USA).…”

Section: Methodsmentioning

confidence: 99%

Neonatal (+)-methamphetamine exposure in rats alters adult locomotor responses to dopamine D1 and D2 agonists and to a glutamate NMDA receptor antagonist, but not to serotonin agonists

Graham

Amos‐Kroohs

Braun

et al. 2012

International Journal of Neuropsychopharmacology

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AbstractNeonatal exposure to (+)-methamphetamine (Meth) results in long-term behavioural abnormalities but its developmental mechanisms are unknown. In a series of experiments, rats were treated from post-natal days (PD) 11–20 (stage that approximates human development from the second to third trimester) with Meth or saline and assessed using locomotor activity as the readout following pharmacological challenge doses with dopamine, serotonin and glutamate agonists or antagonists during adulthood. Exposure to Meth early in life resulted in an exaggerated adult locomotor hyperactivity response to the dopamine D1 agonist SKF-82958 at multiple doses, a high dose only under-response activating effect of the D2 agonist quinpirole, and an exaggerated under-response to the activating effect of the N-methyl-d-aspartic acid (NMDA) receptor antagonist, MK-801. No change in locomotor response was seen following challenge with the 5-HT releaser p-chloroamphetamine or the 5-HT2/3 receptor agonist, quipazine. These are the first data to show that PD 11-20 Meth exposure induces long-lasting alterations to dopamine D1, D2 and glutamate NMDA receptor function and may suggest how developmental Meth exposure leads to many of its long-term adverse effects.

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Dose dependence of the 5-HT agonist quipazine in facilitating spinal stepping in the rat with epidural stimulation

Cited by 55 publications

References 22 publications

Step Training Reinforces Specific Spinal Locomotor Circuitry in Adult Spinal Rats

Step Training Reinforces Specific Spinal Locomotor Circuitry in Adult Spinal Rats

Serotonergic activation of locomotor behavior and posture in one-day old rats

Neonatal (+)-methamphetamine exposure in rats alters adult locomotor responses to dopamine D1 and D2 agonists and to a glutamate NMDA receptor antagonist, but not to serotonin agonists

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