Spontaneous Motor Activity In Rats Research Articles

Accelerated high-frequency repetitive transcranial magnetic stimulation enhances motor activity in rats

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is currently accepted as an evidence-based treatment option for treatment-resistant depression (TRD). Additionally, HF-rTMS showed beneficial effects on psychomotor retardation in patients. The classical HF-rTMS paradigms however are unlikely to replace electroconvulsive therapy, a more potent alternative for TRD albeit with important side-effects. Therefore, recent studies have investigated ‘accelerated’ HF-rTMS protocols demonstrating promising clinical responses in patients with TRD. Since the neuronal effects of accelerated HF-rTMS are underinvestigated, we evaluate here the possible metabolic and neurochemical effects of this treatment alternative. More specifically, we measured the effect on brain glucose metabolism and monoamines/metabolites, as well as on the spontaneous motor activity in rats. We found that brain glucose metabolism and monoamines remained generally unaffected after accelerated HF-rTMS, with the exception of reduced total striatal 5-hydroxyindolacetic acid (a metabolite of serotonin) levels. Interestingly, when compared to sham stimulation, the velocity, the total distance traveled as well as the percentage of movement, as measured by the open-field test, were significantly enhanced after accelerated HF-rTMS showing an increased motor activity.Our current results indicate that the accelerated HF-rTMS-induced increase in motor activity in rats, may be related to the striatal neurochemical effect.

P.1.h.013 - Experimental investigation of the effects of fluoxetine and mianserin on the spontaneous motor activity in rats

P.1.h.013 - Experimental investigation of the effects of fluoxetine and mianserin on the spontaneous motor activity in rats

Acetaldehyde sequestration by D-penicillamine prevents ethanol relapse-like drinking in rats: evidence from an operant self-administration paradigm.

Previous experiments in our laboratory have shown that D-penicillamine (DP) (acetaldehyde sequestering agent) is able to block the increase in ethanol consumption observed after a period of imposed deprivation (the so-called alcohol deprivation effect (ADE)), using a non-operant paradigm in Wistar rats. This study is aimed at investigating the robustness and reproducibility of our previous data using an operant paradigm, which is considered to be a valid and reliable model of human drug consumption, and the ADE, probably the most often used measure of ethanol relapse-drinking behaviour in rats. Male Wistar rats with a limited (30-min sessions), intermittent and extended background of ethanol operant self-administration were used. In order to evaluate the efficacy of several DP doses (6.25, 12.5 and 25mg/kg i.p.) in preventing alcohol relapse, we set up a protocol based on the ADE. In a separate experiment, the effect of DP on spontaneous motor activity of rats was also tested. A significant ADE was observed in animals treated with saline. DP treatment blocked the increase in ethanol responses following the imposed abstinence period. The higher dose suppressed the ADE and provoked a significant reduction in ethanol consumption with respect to the baseline conditions. Basal motor activity was not altered after DP treatment. Our positive results with DP, using two different paradigms that evaluate relapse of ethanol drinking, will help to increase the positive predictive value of pre-clinical experiments and offer a solid base to inspire human studies with DP.

Characteristics of Spontaneous Motor Activity in Neonatal Rats in a Novel Context

We report here our studies of spontaneous motor activity in rat pups in the first two weeks of life. Increased levels of activity followed by decreases during testing could be seen by day 6 of life in rat pups, persisting to more adult animals. These behavioral changes resulted from simultaneous increases in the mobility not only of the forelimbs, but also the hindlimbs. Analysis of the dynamics of activity provides evidence that from day 6 of life, more than 84% of the variability in this parameter is described by two major components. The second component, explaining the elevated level of activity of rat pups in the first minute of the test and its subsequent decrease, is independent of the first component, which determines the baseline level of activity at 3–5 min of testing and is associated with the formation of the pyramidal tract.

Delayed response in the rat frontal lobe transcriptome to perinatal exposure to the flame retardant BDE‐47

BDE-47 is the most prevalent congener of polybrominated diphenyl ethers, which are widely used flame retardants, and is known for endocrine and behavioral disrupting properties in animals. Transient effect on spontaneous motor activity in rats following perinatal exposure to BDE-47 at low doses, relevant to human exposure, was reported in our previous study. The objective of this study was to screen for the long-term effects on gene expression in the brain of rats perinatally exposed to BDE-47. Wistar dams were exposed to BDE-47 (0.002 and 0.2 mg kg(-1) body weight) from gestation day 15 to postnatal day (PND) 20. Total RNA was extracted from the whole brain at PND10 and the brain frontal lobes at PND41 and hybridized to whole-genome RNA expression microarrays. The genes, differentially expressed 1.5-fold, were analyzed with the DAVID bioinformatics resources for cluster and gene-term enrichment. At PND41, clusters of genes involved in nerve impulse transmission, nervous system development and functioning, and core biosynthetic process were altered, including several downregulated genes of cation channels. Representation of LINE1 RNA was decreased significantly. Altered expression of genes involved in neurodevelopment occured at least 3 weeks after the last exposure and the behavioral manifestation of low dose BDE-47 toxicity.

Hypotensive effect and toxicology of the extract from Coscinium fenestratum (Gaertn.) Colebr.

The water extract from Coscinium fenestratum (Gaertn.) Colebr. (CF extract) was tested for hypotensive and vasorelaxant effects. Acute and subchronic toxicity as well as motor activity of CF extract were also evaluated. The present study demonstrates that CF extract is effective in reducing blood pressure in anesthetized normotensive rats. This effect is shown to be dose-related and rapid in onset. The extract showed an endothelium-dependent and independent vasorelaxant activity in isolated aortic rings precontracted with phenylephrine (1 μM) and KCl (60 mM). The capacity of l-NAME (100 μM), an inhibitor of nitric oxide synthase, to reduce the vasorelaxant action of the extract indicates the involvement of nitric oxide. In the acute toxicity test, an oral dose of 5000 mg/kg of the CF extract did not produce mortality or significant changes of the general behavior of animals and gross appearance of internal organs of rats. Similarly, in the subchronic toxicity test, an oral dose of 2500 mg/kg/day of the CF extract given to rats for 90 days did not cause any significant change of any of the parameters observed when compared with those of the control animals. Moreover, the CF extract did not produce any effect on the central nervous system when spontaneous motor activity in rats was assessed. However, because some average hematological and blood chemistry values were found to be statistically different, further studies, including chronic toxicity test, should be done to confirm the safety of this plant when it is used over a long period of time.

Effects of RGH-237 [N-{4-[4-(3-Aminocarbonyl-phenyl)-piperazin-1-yl]-butyl}-4-bromo-benzamide], an Orally Active, Selective Dopamine D3Receptor Partial Agonist in Animal Models of Cocaine Abuse

Dopamine D(3) receptor partial agonism has been suggested as a potential therapeutic intervention in cocaine addiction. RGH-237 [N-{4-[4-(3-aminocarbonyl-phenyl)-piperazin-1-yl]-butyl}-4-bromo-benzamide] was identified as a novel selective dopamine D(3) receptor partial agonist and used for testing this hypothesis in animal models. The compound showed nanomolar affinity to human (K(i) = 6.7 nM) and rat (K(i) = 1.6 nM) D(3) receptors with an intrinsic activity of approximately 50%. It possessed several hundredfold selectivity over the D(2) receptor. The molecule bound with moderate (100-250 nM) affinity to 5-hydroxytryptamine 1A (5-HT(1A)) and nonselectively labeled opiate receptors. RGH-237 proved to be practically inactive on more than 40 other targets, including monoaminergic, cholinergic, GABAergic, and glutamatergic receptors. In rats orally administered RGH-237 was well and rapidly absorbed yielding 41% oral bioavailability. At its pharmacologically active dose (10 mg/kg p.o.), the brain concentration of RGH-237 reached 110 ng/g. Its blood and brain levels were sustained for 3 h. RGH-237 at the oral dose of 10 mg/kg moderately but significantly inhibited the acquisition of cocaine-induced place preference, although by itself, it had no place-conditioning effect. The compound did not affect fixed ratio 1 cocaine self-administration. In a reinstatement paradigm of cocaine self-administration, the compound potently and dose-dependently blocked the cue-induced cocaine-seeking behavior of rats at 10 and 30 mg/kg oral doses. RGH-237 did not affect seeking activity for natural rewards, such as sucrose and water. It did not exert notable effect on spontaneous motor activity of rats. Our results demonstrate that selective D(3) partial agonists may be an effective therapeutic means in the treatment of cocaine abuse.

The Effect of Extremely Low‐Frequency Magnetic Field on Motor Activity of Rats in the Open Field

Exposure to extremely low-frequency magnetic field (ELF-MF, 50 Hz, 0.5 mT) for seven days did not change spontaneous motor activity of rats in the open field compared to sham-exposed animals. Pre-exposure to ELF-MF decreased locomotor and stereotypic activity induced by amphetamine (1.5 mg/kg body weight) and accordingly increased the resting time compared to sham-exposed and amphetamine-treated rats. Vertical activity (rearing) of these two groups was similar. Our results indicate that ELF-MF has different effects on some parameters of amphetamine-induced motor activity, probably due to brain region-specific effects on catecholaminergic systems responsible for movement control.

Synthesis and Pharmacological Properties of 1-Aryl-4-(3′4′,5′-trimethoxybenzoyl)piperazines

A series of 1-aryl-4-(3′,4′,5′-trimethoxybenzoyl)piperazines (IIa - IIg) having structures containing 3,4,5-trimethoxybenzoyl fragments were synthesized and characterized. Compounds IIa and IIc - IIg demonstrated weak anxiolytic properties and moderately decreased the spontaneous motor activity in rats. Compound IIb exhibited anxiolytic activity comparable with that of buspirone but, in contrast to this reference drug, increased the motor activity of test animals.

Intracerebroventricular administration of endothelin-1 impairs the habituation of rats to a novel environment in conjunction with brain serotonergic activation

The effects of i.c.v. administration of endothelin-1, at a low dose that does not produce abnormal behaviors such as barrel-rolling, on the emotional state of rats exposed to a novel environment were examined. Changes in the emotional state of rats with a novel environment were evaluated in terms of changes in exploratory activity in the hole-board apparatus, i.e., locomotor activity as well as the number and duration of rearing and head-dipping behaviors. Rats treated with i.c.v. saline showed marked exploratory behaviors immediately after exposure to the hole-board apparatus, but these exploratory behaviors decreased rapidly with time. On the other hand, the habituation of rats to a novel environment was prolonged by the i.c.v. administration of endothelin-1 (0.3 and 1 pmol). Furthermore, we also found that i.c.v. administration of endothelin-1 (1 pmol) significantly increased the serotonin (5-hydroxytryptamine) turnover in some brain regions, i.e., the cerebral cortex, hippocampus and midbrain, and the inhibition of brain 5-hydroxytryptamine synthesis by treatment with p-chlorophenylalanine (200 mg/kg/day, s.c.) for 2 days suppressed the behavioral effects of endothelin-1 (1 pmol, i.c.v.). In addition, i.c.v. administration of endothelin-1 (1 pmol) did not affect the spontaneous motor activity of rats. The present study demonstrated that i.c.v. administration of low doses of endothelin-1 impairs the habituation of rats to a novel environment in conjunction with brain 5-hydroxytryptaminergic activation. These results suggest that the central endothelin system may play a significant role in mediating emotionality.

Effects of insulin-produced hypoglycemia in combination with ethanol on spontaneous motor activity in rats

The hazardous consequences of drinking alcohol by persons receiving insulin treatment is indicated by clinical reports, but little controlled research has investigated the combination of hypoglycemia and ethanol intoxication. Ethanol's effect on spontaneous motor activity (SMA, detected by Opto-Varimax activity meters) in hypoglycemic (HG) rats was determined over a range of ethanol doses in two experiments. Combinations of insulin and ethanol were administered intraperitoneally to moderately food-deprived rats. Blood glucose was measured before and after a 30-min SMA-monitoring period. In Experiment 1, ethanol doses of 300, 600 and 1200 mg/kg were combined with insulin at doses 0.5 and 2 U/kg. A second experiment tested a narrower range of drug doses (ethanol 600 and 1200 mg/kg, insulin 1 U/kg) under slightly different procedures. After insulin treatment, blood-glucose levels dropped to approximately 40–60% of control levels and this HG was accompanied by decreased SMA. Ethanol did not influence blood-glucose levels, nor did it potentiate the HG produced by insulin. Combination of HG and the highest ethanol dose potentiated the SMA-depressant effect in both experiments, whereas lower ethanol doses partially reversed the suppression of motor activity in HG rats.

Oxytocin enhances the effects of clonidine on blood pressure and locomotor activity in rats

Oxytocin treatment decreases blood pressure and changes the pattern of spontaneous motor activity. The aim of this study was to explore if alpha 2-adrenoreceptors that are involved in the regulation of blood pressure and spontaneous motor activity are influenced by oxytocin treatment. For this purpose, male rats were pretreated with oxytocin (1 mg/kg subcutaneously (s.c.)) or saline once a day during 5 days. Clonidine (alpha 2-adrenoreceptor agonist) decreased blood pressure (2.5 μg/kg intracerebroventricularly (i.c.v.) and 100 μg/kg s.c.) and changed spontaneous motor activity (100 μg/kg s.c.), observed in an open field arena, significantly more in oxytocin pretreated rats compared to saline pretreated controls ( P<0.05). In contrast, idazoxan (alpha 2-adrenoreceptor antagonist) (50 μg/kg i.c.v.) caused a significantly smaller elevation of blood pressure in the oxytocin pretreated rats ( P<0.05). In addition, the effect on blood pressure of an alpha 1-adrenoreceptor agonist, phenylephrine, was evaluated. It increased blood pressure equally in the oxytocin- and saline pretreated rats. The present study shows that subchronic oxytocin treatment increases the effects of clonidine on blood pressure and spontaneous motor activity in rats. These findings imply that alpha 2-adrenoreceptors are involved in the effects of oxytocin treatment on blood pressure and spontaneous motor activity.

Behavioral Effects of Flibanserin (BIMT 17)

Flibanserin is a 5-HT 1A agonist that, in contrast to other 5-HT 1A receptor agonists, is capable of activating 5-HT 1A receptors in frontal cortex. Flibanserin also behaves as an antagonist at 5-HT 2A receptors. This compound has been described to be a putative fast-acting antidepressant owing to these properties. In the present study, the effect of flibanserin was investigated in several behavioral paradigms different from animal models of depression. Intraperitoneal flibanserin, at doses of 4–8 mg/kg, antagonized d-amphetamine– and (+)SKF-10047– induced hypermotility in mice and rats. At doses of 8–16 mg/kg, flibanserin exerted anxiolytic-like effects in the light/dark exploratory test and stress-induced hyperthermia in mice, and antagonized d-amphetamine– and apomorphine-induced stereotypy in rats. At the dose of 16 mg/kg, flibanserin reduced spontaneous motor activity in rats. At the dose of 32 mg/kg, flibanserin did not exert any clear effect on spontaneous motor activity in mice, or on the elevated plus-maze and the water maze in rats.

Neem (Azadirachta indica) treatment decreases spontaneous motor activity in rats: implications for its central sedative action

The administration of a crude steroidal extract of neem (Azadirachta indica A. Juss) leaf significantly decreased the total spontaneous motor activity (SMA) scores in rats receiving either 100 mg/kg body weight (i.p.) twice per week for 6 weeks (p <0.01) or a single dose (p <0.05), indicating that neem may have a sedative effect on rats. Single dose (acute) treatment also significantly decreased (p <0.01) the amplitude of the peak twitch force of the gastrocnemius muscle in vivo, but the neem extract exerted no significant effect on amplitude or conduction velocity of the compound action potential of the toad sciatic nerve preparation in vitro. It is therefore concluded that the depression of the SMA may be due to an effect of neem on the central nervous system and/or muscle strength, but not on peripheral nerve conduction. © 1997 John Wiley & Sons, Ltd.

Changes in the amounts of neurotransmitters released from the striatum and spontaneous motor activity in rats exposed to high doses of toluene.

We studied the neurotoxicological effects of high-dose toluene exposure by measuring neurotransmitter release from the striatum and spontaneous motor activity in freemoving Tokai High Avoider (THA) male rats. The rats were exposed to 1,000, 2,000, and 4,000ppm toluene for 4 hours. During the 4-hour exposure period and each one hour pre- and post-exposure periods, acetylcholine (ACh), 3, 4-dihydroxyphenylacetic acid (DOPAC), homovanilic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the microdialysate from kthe striatum of each rat were measured continuously using microdialysis. Simultaneously, spontaneous motor activity of each rat was monitored using an Aimex device. The amounts of neurotransmitters released and spontaneous motor activity showed similar changes for every concentration of toluene exposure during those periods. Although minimal changes in neurotransmitters and motor activity were observed in the 1,000 ppm group, increases in neurotransmitter release and motor activity were observed in the 2,000 ppm group during the entire exposure period and also in the 4,000 ppm group during the early period of exposure. On the other hand, decreases in neurotransmitter release and motor activity were observed in the 4,000 ppm group during the late period of exposure. These findings indicate that the striatum influences motor activity via changes in the amounts of neurotransmitters released during the period of high-dose toluene exposure.

Synthesis and histamine H 1-receptor antagonist activity of 4-(diphenylmethyl)-1-piperazine derivatives with a terminal heteroaryl or cycloalkyl amide fragment

New 4-(diphenylmethyl)-1-piperazine derivatives with a terminal heteroaryl or cycloalkyl amide fragment were synthesized and evaluated for their antihistaminic, anticholinergic and antiallergic activities. Tested compounds were found to be moderate to potent in vitro (guinea-pig ileum) histamine H(1)-receptor antagonists. Derivatives with a four methylene chain (1e-1h) were as potent in vivo (capillary permeability in rats) as cetirizine; the heteroaryl derivatives 1e and 1h were found to be the most active agents. These compounds displayed only weak in vitro (guinea-pig ileum) muscarinic M(3)-receptor antagonist activity. Compounds 1e and 1g were about 100 times more potent than ketotifen in preventing the compound 48/80-induced histamine release from rat peritoneal mast cells. Derivatives 1e, 1f and 1h did not modify the spontaneous motor activity in rats at 100 mg/kg po. Compound 1e has been selected for further studies.

Central Nervous System Toxicity of Manganese: I. Inhibition of Spontaneous Motor Activity in Rats after Intrathecal Administration of Manganese Chloride

Central Nervous System Toxicity of Manganese. I. Inhibition of Spontaneous Motor Activity in Rats after Intrathecal Administration of Manganese Chloride. Ingersoll, R. T., Montgomery, E. B., Jr., and Aposhian, H. V. (1995). Fundam. Appl. Toxicol. 27, 106-113. The intrathecal administration of MnCl 2 to young male rats caused dopamine depletion in the caudate-putamen and a decrease in spontaneous motor activity. Our experiments demonstrate that in the young rat; (a) the lateral choroid plexus protects the cerebrospinal fluid (CSF) from high concentrations of Mn in the blood by sequestering and thus preventing large amounts of this metal ion from entering the CSF. As blood Mn levels rise, the lateral choroid plexus may become overwhelmed and leak an increasing amount of Mn into the CSF. (b) The lateral choroid plexus does not remove Mn 2+ from the CSF. (c) The injection of MnCl 2 into the CSF of rats caused a rapid decrease in spontaneous motor activity which is dose-dependent and reversible under the present experimental conditions. Intrathecal Mn results in a substantial decrease in striatal dopamine but not homovanillic acid or 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations and is associated with an increase in the Mn concentration of the substantia nigra and caudate-putamen.

The pharmacology of VA21B7: an atypical 5-HT3 receptor antagonist with anxiolytic-like properties in animal models.

VA21B7 (3-[2-(4'-piperonylpiperazinyl) indolyl] carboxaldehyde) was synthesized as a potential 5-HT3 receptor antagonist. Even though VA21B7 showed a higher affinity towards 5-HT3 receptors as compared to other receptors studied, it was not a potent 5-HT3 receptor antagonist either in the periphery or in the brain. In a simple animal model of anxiety such as the two-compartment box in mice, a remarkable anxiolytic-like effect was found at doses of 2-500 micrograms/kg IP and also at low oral doses, in the microgram range. These drug doses did not produce any significant effect on spontaneous motor activity of mice. The anxiolytic profile of VA21B7 was further explored using other models of anxiety in rats such as the elevated plus-maze and punished-drinking. VA21B7 was compared with standard 5-HT3 receptor antagonists such as ondansetron, tropisetron and granisetron, with the 5-HT1A agent buspirone and with diazepam. In the plus-maze, VA21B7 showed an anxiolytic-like profile after doses of 0.25-0.5 mg/kg IP or 2-4 mg/kg PO which did not modify the number of total entries into the open and closed arms of the maze. Diazepam, granisetron and tropisetron were also effective in this test but not ondansetron and buspirone. VA21B7 was also able to release suppressed behaviour in the punished-drinking test. The dose-response curve was bell-shaped with a peak at 2-4 mg/kg. At variance with other studies, 5-HT3 receptor antagonists also increased the number of shocks taken in this test and the dose-response curve was also bell-shaped. VA21B7 was not anticonvulsant like diazepam, its anxiolytic action in the light/dark test was not flumazenil-sensitive and there was no rebound anxiogenic effect on withdrawal from chronic VA21B7 treatment for 15 consecutive days. Moreover, VA21B7 was not amnesic like the benzodiazepines but low doses of 2-4 mg/kg reduced the memory deficits induced in rats by scopolamine. Much higher doses were necessary to decrease spontaneous motor activity in rats. Since VA21B7 appears to be well tolerated in rodents at high doses, we think that it is of potential interest as an anxiolytic in humans.

Reversal of behavioral changes in rats subjected to portacaval shunt with oral neomycin therapy

The portacaval shunt rat is often used as a model of human portal-systemic encephalopathy, but its relevance to human portal-systemic encephalopathy remains uncertain. Specifically, it has not been demonstrated that the behavioral changes seen in this model respond to measures known to improve portal-systemic encephalopathy in human subjects. Accordingly, the aim of this study was to establish whether neomycin (an effective treatment for portal-systemic encephalopathy in human beings) added to the drinking water of rats subjected to portacaval shunt reversed or ameliorated the reduction in spontaneous motor activity, which represents a measure of encephalopathy in this animal model. A randomized, placebo-controlled crossover design was used, with each animal serving as its own control. After establishment of baseline activities, 12 rats with portacaval shunt and 12 sham-operated rats were divided into two equal groups: Group A animals received neomycin for 1 wk; this was followed by 1 wk off neomycin; in group B rats, the sequence was reversed. Spontaneous intake of neomycin for 7 days at doses comparable to human usage (0.1 to 0.2 gm/kg/day) was associated with a significant increase in spontaneous motor activity in rats subjected to portacaval shunt (26.4% in group A, 66.3% in group B; p < 0.01 for each protocol) with no significant effect in sham-operated animals. Withdrawal of neomycin resulted in reversal of this effect in group A rats subjected to portacaval shunt. Similar significant improvements for exploratory activity as measured on the basis of nose-hole pokes was also seen in rats subjected to portacaval shunt and given neomycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between circadian changes in spontaneous motor activity and dorsal versus ventral striatal dopamine neurotransmission assessed with on-line microdialysis.

The relationship between circadian changes in spontaneous motor activity in rats and dopamine (DA) neurotransmission in the dorsal or ventral striatum was assessed with on-line in vivo microdialysis. The concentration of DA and DA metabolites in the dorsolateral caudate nucleus increased significantly at night. In contrast, DA in the nucleus accumbens did not change significantly across the light-dark cycle. The concentration of DA metabolites in the nucleus accumbens did show circadian variation, however, which was comparable with that seen in the dorsolateral caudate nucleus. Although there was a significant positive correlation between the concentration of DA in both the dorsal and ventral striatum and spontaneous nocturnal motor activity, the relationship was very weak, especially for the accumbens. This suggest that regulating the level of spontaneous motor activity per se is not a primary function of the mesostriatal DA system.