scholarly journals Dopaminergic Modulation of Forced Running Performance in Adolescent Rats: Role of Striatal D1 and Extra-striatal D2 Dopamine Receptors

2021 ◽  
Author(s):  
Angel Toval ◽  
Daniel Garrigos ◽  
Yevheniy Kutsenko ◽  
Miroljub Popović ◽  
Bruno Ribeiro Do-Couto ◽  
...  
Keyword(s):  
Open Field ◽  
Exercise Capacity ◽  
Motor Behavior ◽  
D2 Receptors ◽  
Sensitive Period ◽  
Dependent Manner ◽  
Running Wheel ◽  
Incremental Test ◽  
Adolescent Rats ◽  
Forced Running

AbstractImproving exercise capacity during adolescence impacts positively on cognitive and motor functions. However, the neural mechanisms contributing to enhance physical performance during this sensitive period remain poorly understood. Such knowledge could help to optimize exercise programs and promote a healthy physical and cognitive development in youth athletes. The central dopamine system is of great interest because of its role in regulating motor behavior through the activation of D1 and D2 receptors. Thus, the aim of the present study is to determine whether D1 or D2 receptor signaling contributes to modulate the exercise capacity during adolescence and if this modulation takes place through the striatum. To test this, we used a rodent model of forced running wheel that we implemented recently to assess the exercise capacity. Briefly, rats were exposed to an 8-day period of habituation in the running wheel before assessing their locomotor performance in response to an incremental exercise test, in which the speed was gradually increased until exhaustion. We found that systemic administration of D1-like (SCH23390) and/or D2-like (raclopride) receptor antagonists prior to the incremental test reduced the duration of forced running in a dose-dependent manner. Similarly, locomotor activity in the open field was decreased by the dopamine antagonists. Interestingly, this was not the case following intrastriatal infusion of an effective dose of SCH23390, which decreased motor performance during the incremental test without disrupting the behavioral response in the open field. Surprisingly, intrastriatal delivery of raclopride failed to impact the duration of forced running. Altogether, these results indicate that the level of locomotor response to incremental loads of forced running in adolescent rats is dopamine dependent and mechanistically linked to the activation of striatal D1 and extra-striatal D2 receptors.

092 Effect of the dual orexin receptor antagonist (DORA) daridorexant on behaviour upon awakening in rats and dogs

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A38-A39
Author(s):  
Giorgio Bergamini ◽  
Catherine Roch ◽  
Sean Durkin ◽  
Michel Steiner
Keyword(s):  
Grip Strength ◽  
Motor Skills ◽  
Muscle Weakness ◽  
Motor Behavior ◽  
Motor Impairment ◽  
Phase Behaviour ◽  
Fine Motor ◽  
Dependent Manner ◽  
The Impact ◽  
Time Point

Abstract Introduction The ability to be fast alert and to interact with the environment without motor impairment upon waking up, is a critical feature of natural sleep. DORAs represent a new class of insomnia medications that specifically inhibit the wake-promoting effects of orexin neuropeptides. Daridorexant is a potent and selective DORA under late stage development for the treatment of insomnia. Here, we assessed the impact of sleep-promoting doses of daridorexant on rats’ and dogs’ behaviour upon forced awakening. Zolpidem (a positive GABAA receptor modulator) was used as active comparator in rats because of its known negative impact on motor functions. Methods Rats were woken up at different time points after oral administration of daridorexant (10, 30, 100 mg/kg) or zolpidem (30, 100 mg/kg) during their inactive phase, and repeatedly subjected to two motor tasks: 1) the rotating rod test (lasting 120 sec, at each time point) assessing gross motor skills and coordination, and 2) the forepaw grip strength test assessing fine motor skills and muscle strength. Dogs were presented with food as an external, salient stimulus, three hours after administration of daridorexant in gelatin capsules (10, 30 or 90 mg/dog) during their active phase. Behaviour and signs of muscle weakness, after having woken up, were assessed by manual inspection of video recordings and concomitant electroencephalogram/electromyogram recordings. Results In both the rotarod and grip tests, daridorexant treatment had no effect on motor behavior at any dose or time point tested, while zolpidem significantly reduced the time spent on the rotarod and the grip strength in a dose and time-dependent manner (N=12/group; p<0.001;) (e.g. at 30 min post-dose, time spent on the rotarod was 84, 79–89 and 10–19 sec for vehicle, daridorexant and zolpidem, respectively). Dogs treated with daridorexant were able to wake up easily upon food presentation. They behaved and ate normally and did not show any signs of muscle weakness. Conclusion The type of sleep promoted by daridorexant is surmountable in rats and dogs and similar to physiological sleep. It allows animals to easily wake up, to behave normally without motor impairment and to respond efficiently to the environmental conditions. Support (if any) Funded by Idorsia Pharmaceuticals Ltd

scholarly journals Evaluation of efforts in untrained Wistar rats following exercise on forced running wheel at maximal lactate steady state

2017 ◽  
Vol 21 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Sajjad Rezaei ◽  
Hamid Agha-alinejad ◽  
Mahdieh Molanouri Shamsi ◽  
Mahvash Jafari ◽  
Fabricio Azevedo Voltarelli ◽  
...  
Keyword(s):  
Steady State ◽  
Wistar Rats ◽  
Maximal Lactate Steady State ◽  
Running Wheel ◽  
Forced Running

scholarly journals Multifactorial motor behavior assessment for real-time evaluation of emerging therapeutics to treat neurologic impairments

2019 ◽  
Author(s):  
Riazul Islam ◽  
Carlos Cuellar ◽  
Ben Felmlee ◽  
Tori Riccelli ◽  
Jodi Silvernail ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Body Weight ◽  
Motor Activity ◽  
Real Time ◽  
Open Field ◽  
Hind Limb ◽  
Motor Behavior ◽  
Motor Evoked Potentials ◽  
Network Activity ◽  
Novel Approach

AbstractIntegrating multiple assessment parameters of motor behavior is critical for understanding neural activity dynamics during motor control in both intact and dysfunctional nervous systems. Here, we described a novel approach (termed Multifactorial Behavioral Assessment (MfBA)) to integrate, in real-time, electrophysiological and biomechanical properties of rodent spinal sensorimotor network activity with behavioral aspects of motor task performance. Specifically, the MfBA simultaneously records limb kinematics, multi-directional forces and electrophysiological metrics, such as high-fidelity chronic intramuscular electromyography synchronized in time to spinal stimulation in order to characterize spinal cord functional motor evoked potentials (fMEPs). Additionally, we designed the MfBA to incorporate a body weight support system to allow bipedal and quadrupedal stepping on a treadmill and in an open field environment to assess function in rodent models of neurologic disorders that impact motor activity This novel approach was validated using, a neurologically intact cohort, a cohort with unilateral Parkinsonian motor deficits due to midbrain lesioning, and a cohort with complete hind limb paralysis due to T8 spinal cord transection. In the SCI cohort, lumbosacral epidural electrical stimulation (EES) was applied, with and without administration of the serotonergic agonist Quipazine, to enable hind limb motor functions following paralysis. The results presented herein demonstrate the MfBA is capable of integrating multiple metrics of motor activity in order to characterize relationships between EES inputs that modulate mono- and polysynaptic outputs from spinal circuitry which in turn, can be used to elucidate underlying electrophysiologic mechanisms of motor behavior by synchronizing these datasets to metrics of movement and behavior. These results also demonstrate that proposed MfBA is an effective tool to integrate biomechanical and electrophysiology metrics, synchronized to therapeutic inputs such as EES or pharmacology, during body weight supported treadmill or open field motor activities, to target a high range of variations in motor behavior as a result of neurological deficit at the different levels of CNS.

scholarly journals Prior exercise impairs subsequent performance in an intensity- and duration-dependent manner

2021 ◽  
Author(s):  
Madison M Fullerton ◽  
Louis Passfield ◽  
Martin J. MacInnis ◽  
Danilo Iannetta ◽  
Juan M Murias
Keyword(s):  
Lactate Threshold ◽  
Peak Power ◽  
Constant Load ◽  
Cycle Ergometer ◽  
Dependent Manner ◽  
Incremental Test ◽  
Subsequent Performance ◽  
Prior Exercise ◽  
Subsequent Time ◽  
Constant Load Exercise

Prior constant-load exercise performed for 30-min at or above maximal lactate steady state (MLSSp) significantly impairs subsequent time-to-task failure (TTF) compared with TTF performed without prior exercise. We tested the hypothesis that TTF would decrease in relation to the intensity and the duration of prior exercise compared to a baseline TTF trial. Eleven individuals (6 men, 5 women, 28 ± 8 yrs) completed the following tests on a cycle ergometer (randomly assigned after MLSSp was determined): i) a ramp-incremental test, ii) a baseline TTF trial performed at 80% of peak power (TTFb), iii) five 30-min constant-PO rides at 5% below lactate threshold (LT-5%), halfway between LT and MLSSp (Delta50), 5% below MLSSp (MLSS-5%), MLSSp, and 5% above MLSSp (MLSS+5%), and iv) 15- and 45-min rides at MLSSp (MLSS15 and MLSS45, respectively). Each condition was immediately followed by a TTF trial at 80% of peak power. Compared to TTFb (330 ± 52s), there was 8.0 ± 24.1, 23.6 ± 20.2, 41.0 ± 14.8, 52.2 ± 18.9, and 75.4 ± 7.4% reduction in TTF following LT-5%, Delta50, MLSS-5%, MLSSp, and MLSS+5%, respectively. Following MLSS15 and MLSS45 there were 29.0 ± 20.1 and 69.4 ± 19.6% reductions in TTF, respectively (P <0.05). It is concluded that TTF is reduced following prior exercise of varying duration at MLSSp and at submaximal intensities below MLSS. Novelty: •Prior constant-PO exercise, performed at intensities below MLSSp, reduces subsequent TTF performance. •Subsequent TTF performance is reduced in a linear fashion following an increase in the duration of constant-PO exercise at MLSSp.

scholarly journals Evaluation of analgesic and neuropharmacological properties of the aerial part of Tinospora cordifolia Miers. in mice

1970 ◽  
Vol 2 (2) ◽  
pp. 31-37 ◽  
Author(s):  
Md Mokarram Hossain ◽  
SM Raquibul Hasan ◽  
Raushanara Akter ◽  
Md Nurul Islam ◽  
Md Jahidur Rashid ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Motor Activity ◽  
Open Field ◽  
Aerial Part ◽  
Tinospora Cordifolia ◽  
Tail Flick ◽  
Dependent Manner ◽  
Writhing Test ◽  
Sleeping Time ◽  
Thiopental Sodium

Tinospora cordifolia Miers. is used in the Ayurvedic system of medicine for the treatment of jaundice, diabetes, and rheumatoid arthritis, and is also used as memory enhancer. But still there is no report of analgesic and neuropharmacological activities of the plant. For this reason, the present study was designed to evaluate analgesic and neuropharmacological activities of methanol extract of the aerial parts of Tinospora cordifolia. Analgesic activity of the crude extract at the dose of 200 and 400 mg/kg b.w. was evaluated for its central and peripheral pharmacological actions using hotplate and tail flick tests and acetic acid-induced writhing test respectively in mice. The extract produced a significant (p < 0.05-0.001) increase in pain threshold in hotplate and tail flick tests in a dose dependent manner. In acetic acid-induced writhing test the extract at both doses produced significant (p < 0.001) inhibition of writhing reaction but maximum inhibition (65.01%) of writhing was found at 400 mg/kg dose compared to the reference drug Diclofenac-Na at the dose of 10 mg/kg b.w. (77.07%). Neuropharmacological activity of the extract was also evaluated using rodent behabioural models; hole cross to evaluate motor activity, open field to evaluate exploratory behaviour and thiopental sodium-induced sleeping time to evaluate sedative potential of the extract. The extract significantly (p < 0.05-0.001) decreased motor activity and exploratory behavior of mice in hole cross and open field test respectively. The extract also produced rapid onset and maximized the duration of sleeping time when administered with thiopental sodium. Results of this study suggest that the aerial part of T. cordifolia possesses significant analgesic and CNS depressant activity.  Key words: Tinospora cordifolia; Menispermaceae; Analgesic; Neuropharmacological.DOI: 10.3329/sjps.v2i2.5822Stamford Journal of Pharmaceutical Sciences Vol.2(2) 2009: 31-37

scholarly journals Multifactorial motor behavior assessment for real-time evaluation of emerging therapeutics to treat neurologic impairments

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Riazul Islam ◽  
Carlos A. Cuellar ◽  
Ben Felmlee ◽  
Tori Riccelli ◽  
Jodi Silvernail ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Body Weight ◽  
Motor Activity ◽  
Real Time ◽  
Open Field ◽  
Hind Limb ◽  
Motor Behavior ◽  
Motor Evoked Potentials ◽  
Network Activity ◽  
Novel Approach

Abstract Integrating multiple assessment parameters of motor behavior is critical for understanding neural activity dynamics during motor control in both intact and dysfunctional nervous systems. Here, we described a novel approach (termed Multifactorial Behavioral Assessment (MfBA)) to integrate, in real-time, electrophysiological and biomechanical properties of rodent spinal sensorimotor network activity with behavioral aspects of motor task performance. Specifically, the MfBA simultaneously records limb kinematics, multi-directional forces and electrophysiological metrics, such as high-fidelity chronic intramuscular electromyography synchronized in time to spinal stimulation in order to characterize spinal cord functional motor evoked potentials (fMEPs). Additionally, we designed the MfBA to incorporate a body weight support system to allow bipedal and quadrupedal stepping on a treadmill and in an open field environment to assess function in rodent models of neurologic disorders that impact motor activity. This novel approach was validated using, a neurologically intact cohort, a cohort with unilateral Parkinsonian motor deficits due to midbrain lesioning, and a cohort with complete hind limb paralysis due to T8 spinal cord transection. In the SCI cohort, lumbosacral epidural electrical stimulation (EES) was applied, with and without administration of the serotonergic agonist Quipazine, to enable hind limb motor functions following paralysis. The results presented herein demonstrate the MfBA is capable of integrating multiple metrics of motor activity in order to characterize relationships between EES inputs that modulate mono- and polysynaptic outputs from spinal circuitry which in turn, can be used to elucidate underlying electrophysiologic mechanisms of motor behavior. These results also demonstrate that proposed MfBA is an effective tool to integrate biomechanical and electrophysiology metrics, synchronized to therapeutic inputs such as EES or pharmacology, during body weight supported treadmill or open field motor activities, to target a high range of variations in motor behavior as a result of neurological deficit at the different levels of CNS.

Oral Monosodium Glutamate Differentially Affects Open-Field Behaviours, Behavioural Despair and Place Preference in Male and Female Mice

2019 ◽  
Vol 8 (2) ◽  
pp. 130-145
Author(s):  
Onaolapo AY ◽  
Olawore OI ◽  
Yusuf FO ◽  
Adeyemo AM ◽  
Adewole IO ◽  
...  
Keyword(s):  
Open Field ◽  
Monosodium Glutamate ◽  
Place Preference ◽  
Dependent Manner ◽  
Adult Mice ◽  
Plus Maze ◽  
Group 3 ◽  
Group 2 ◽  
Behavioural Tests ◽  
Conditioned Place Preference Paradigm

Background: Monosodium glutamate (MSG) is a flavour enhancer which induces behavioural changes in animals. However the influence of sex on the behavioural response to MSG has not been investigated. Objective: The sex-differential effects of MSG on open-field behaviours, anxiety-related behaviour, behavioural despair, place-preference, and plasma/brain glutamate levels in adult mice were assessed. Methods: Mice were assigned to three groups (1-3), based on the models used to assess behaviours. Animals in group 1 were for the elevated-plus maze and tail-suspension paradigms, group 2 for the open-field and forced-swim paradigms, while mice in group 3 were for observation in the conditioned place preference paradigm. Mice in all groups were further assigned into five subgroups (10 males and 10 females), and administered vehicle (distilled water at 10 ml/kg) or one of four doses of MSG (20, 40, 80 and 160 mg/kg) daily for 6 weeks, following which they were exposed to the behavioural paradigms. At the end of the behavioural tests, the animals were sacrificed, and blood was taken for estimation of glutamate levels. The brains were also homogenised for estimation of glutamate levels. Results: MSG was associated with a reduction in locomotion in males and females (except at 160 mg/kg, male), an anxiolytic response in females, an anxiogenic response in males, and decreased behavioural despair in both sexes (females more responsive). Postconditioning MSG-associated place-preference was significantly higher in females. Plasma/ brain glutamate was not significantly different between sexes. Conclusion: Repeated MSG administration alters a range of behaviours in a sex-dependent manner in mice.

Chronic inositol increases striatal D2 receptors but does not modify dexamphetamine-induced motor behavior

2001 ◽  
Vol 68 (2) ◽  
pp. 245-253 ◽  
Author(s):  
Brian H Harvey ◽  
Andre Scheepers ◽  
Linda Brand ◽  
Dan J Stein
Keyword(s):  
Motor Behavior ◽  
D2 Receptors
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