Increase In Spontaneous Motor Activity Research Articles

Behavioral Responses and Immune and Cytogenetic Parameters of Food-Restricted Mice.

The experiments on mice showed that subchronic food restriction to 40 and 8% of unrestricted ration is a strong stressor inducing devastation of lymphoid organs, primarily the thymus and spleen. The mice in the group with severe food restriction (8% of normal ration) demonstrated increased front paw grip force. We also observed an increase in spontaneous motor activity in these animals correlated with food restriction. Food deprivation led to inhibition of proliferative activity of the bone marrow cells and suppression of erythropoiesis. Moreover, severe food restriction was accompanied by a decrease in the number of double-strand DNA breaks evaluated by the release of γH2AX+-cells and the ratio of polychromatophilic erythrocytes.

Effect of various extracts of Justicia gendarussa leaves on neuropharmacological behavior activity in MPTP induced mice model

The present research work is assessment of various extracts of Justicia gendarussa (JG) leaves on neuropharmacological behavior studies in MPTP induced mice model. Animals were administered with Ethanol, Ethyl acetate, Aqueous and n-hexane extracts at dose 200 and 400mg/kg orally along with MPTP (20mg/kg I.P) 4 injections on day 1 and L-DOPA(100mg/kg I.P) was used as standard. Treatment was continued for 7 days and behavioral assessment was made by spontaneous motor activity, number of head dippings (alertness), rota rod test(grip strength) and immobility time by Tail suspension test (TST) and Forced swimming test(FST) on 1st, 4th and 7th day of treatment. The results of the present study showed that spontaneous motor activity, retention time on rota rod and number of head dipping were decreased (P<0.001) whereas, immobility time in TST and FST were increased (P<0.01) in MPTP induced animals. While the motor scores, alertness and retention time (P<0.001) were increased and immobility time in TST and FST(P<0.01) were decreased significantly and dose dependently with ethanol, ethyl acetate and aqueous extracts on 4th and 7th day of treatment as compared with MPTP, L-dopa and normal control, where as n-hexane extract showed slight activity. Preliminary phytochemical analysis of all the extracts showed presence of flavonoids, poly phenols, amino acids, proteins, terpenoids, carbohydrates, tannins and alkaloids. It was observed that ethanol extract of JG at a dose of 400mg/kg on 7th day exhibited maximum increase in spontaneous motor activity, retention time and number of head dipping and decrease in immobility time in TST and FST as compared to Control, MPTP and L-Dopa treated animals. Evidence of above observations, Justicia gendarussa leaves may be suggested as a potential source for CNS stimulant activity with neuroprotective effect. The effect may be due to presence of L-dopa like compounds, terpenoids, flavonoids -polyphenols (Naringenin), amino acids like tyrosine and proteins.

The effects of the relict microorganism B. sp. on development, gas exchange, spontaneous motor activity, stress resistance, and survival of Drosophila melanogaster

Relict microorganisms preserved in the permafrost of geological periods possess a unique resistance to unfavorable factors of the internal and external environment. Their metabolic, DNA repair, and growth capacities are still under discussion, but the very fact of their existence in permafrost during many thousands of years is evidence of their phenomenal viability. One of these bacteria (B. sp.) that was found in Yakutia and that proved to be capable of enhancing longevity and immunity in drosophila and mice (A.V. Brushkov et al., 2009) was tested in developing drosophila fruit flies as follows: a culture of B. sp. (1 to 500 million/ml) was added to the nutrient medium of Drosophila melanogaster and a set of indices characterizing growth rate and mortality at the larval and pupal stages was investigated. The level of gas exchange (\(V_{O_2 }\) and \(V_{CO_2 }\)), body weight, and stress resistance were investigated in imagoes hatched under these conditions. B. sp. induces dose-dependent growth acceleration and decrease in larval mortality. The increase in spontaneous motor activity, \(V_{O_2 }\) and \(V_{CO_2 }\), and body weight, as well as resistance to heat shock and UV irradiation, were demonstrated for imagoes.

Intrastrial injection of magnesium after picrotoxin does not reduce motor hyperactivity in rats

Magnesium chloride injected into rat rostral neostriatum before picrotoxin prevents motor hyperactivity induced by this GABAA receptor antagonist: prevents the increase in spontaneous motor activity in the open field test and reduces reproduction and duration of choreic hyperkinesia. Injection of magnesium 15 min after picrotoxin virtually did not modify the hyperkinetic effects of picrotoxin. The results indicate the role of calcium processes in the appearance of strial picrotoxin hyperactivity and principal possibility of its correction with magnesium only before the cascade of respective calcium ionic transformations is triggered in the brain.

Oxytocin decreases corticosterone and nociception and increases motor activity in OVX rats

Objectives: In the present study the effects of oxytocin administered subcutaneously (s.c.) or intravaginally (i.vag.) on spontaneous motor activity, nociceptive thresholds and plasma corticosterone levels were examined in female ovariectomized (OVX) rats. Methods: Oxytocin (1 mg/kg s.c. or 100 μg i.vag.) was administered once a day for 10 days to OVX rats. Controls received saline s.c. or cellulose gel i.vag. Spontaneous motor activity was observed in an open-field arena, nociceptive thresholds were investigated by the tail-flick test, and corticosterone and oxytocin plasma levels were measured by radioimmunassay, 3, 4 and 5 days respectively, after the end of the treatment period. Results: Both oxytocin administered s.c. and i.vag. increased forward locomotion ( p < 0.05) and nociceptive thresholds ( p < 0.05) significantly. In addition, oxytocin s.c. increased the amount of locomotor activity ( p < 0.05). Plasma corticosterone levels were decreased ( p < 0.05) and oxytocin levels were unchanged when measured 5 days after the last administration of oxytocin s.c. or i.vag. Conclusion: The present data indicate that oxytocin induces a spectrum of long-lasting effects in OVX rats, including an increase in spontaneous motor activity, elevation of nociceptive thresholds and decrease of corticosterone levels. Similar effects may be induced by estrogens. In addition, these data indicate that i.vag. administration of oxytocin may be used to induce oxytocin-mediated effects.

Neurobehavioural defects in adult mice neonatally exposed to nicotine: changes in nicotine-induced behaviour and maze learning performance

Neonatal exposure to low doses of nicotine has been shown to disturb the development of low-affinity nicotinic binding sites in the cerebral cortex and to elicit a deviant behavioural response to nicotine in adult mice. In this study, 10-day-old male NMRI mice were exposed to one of three different doses of nicotine (3.3, 33, or 66 μg nicotine-base/kg body wt.) s.c. twice daily on 5 consecutive days to study dose–response effects of nicotine on adult spontaneous and nicotine-induced motor behaviour. The nicotine-induced behaviour test revealed a hypoactive response to nicotine in 4-month-old mice neonatally exposed to 33 or 66 μg nicotine-base, whereas the response to nicotine in control animals and mice exposed to 3.3 μg nicotine-base was an increased activity. Learning and memory functions were also investigated in adult animals neonatally exposed to 66 μg nicotine-base/kg body wt. in the same manner, in the Morris water maze and in the Radial arm maze. In the swim maze and the Radial arm maze tests, no significant differences were observed between nicotine-treated and control animals at the age of 4 months. At 7 months, however, a significant difference in performance was evident, indicating a time-response/time-dependent effect. Furthermore, it was shown that in mice exposed neonatally to a nicotine dose known to inhibit the development of the nicotinic low affinity-binding site (LA), the response to nicotine could not cause any increase in spontaneous motor activity as seen in controls.

Behavioral responses of hatchling painted turtles ( Chrysemys picta) and snapping turtles ( Chelydra serpentina) at subzero temperatures

We monitored behavioral responses of cold-acclimated hatchling painted turtles ( Chrysemys picta) indigenous to Nebraska and hatchling snapping turtles ( Chelydra serpentina) indigenous to Nebraska and Arkansas during cooling (0.1°C/min) to temperatures as low as −19°C. All turtles made exploratory movements during cooling and locomotion occurred at temperatures as low as −2 to −4°C, but C. picta maintained relatively higher levels of locomotor activity than C. serpentina, and no differences in motility occurred between northern and southern groups of C. serpentina. Slow movements of the head and limbs were observed in supercooled hatchling C. picta at temperatures as low as −10°C, whereas at about −5°C, C. serpentina exhibited an increase in spontaneous motor activity followed by muscle contracture, immobility, and spontaneous freezing. C. picta spontaneously froze at about −16°C without exhibiting cold contracture, suggesting that they are better adapted to survive exposure to extreme cold.

Differences between haloperidol- and pimozide-induced withdrawal syndrome: a role for Ca 2+ channels

We investigated the behavioral and biochemical events appearing in rats after withdrawal for 24 h or 8–12 days from two classical neuroleptics, haloperidol and pimozide. The neuroleptics were given for 14 days alone or shortly after injection of the Ca 2+ channel blocker nifedipine. We have found that withdrawal effects after haloperidol and pimozide were different. After haloperidol treatment we observed an increase in cortical Ca 2+ channel and limbic dopamine D 1 receptor density and an increase in spontaneous motor activity and apomorphine-induced hyperactivity and stereotypy. In contrast no biochemical changes were observed during pimozide withdrawal, and locomotor activity and responses to apomorphine were depressed. Co-administration of nifedipine with haloperidol prevented the observed biochemical and behavioral symptoms of withdrawal. Nifedipine administration did not change the depressant effects of pimozide. Our results suggest that the voltage-dependent Ca 2+ channel is involved in the observed withdrawal syndrome of neuroleptics, and that the absence of this syndrome after pimozide may be related to its considerable Ca 2+ channel-blocking properties.

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)

Interaction of taurine and related compounds with GABAergic neurones in the nucleus raphe dorsalis

The effects of GABA A (muscimol) and GABA B (baclofen) receptor agonists on spontaneous motor activity and food consumption of rats were compared to those produced by taurine and related compounds (3-aminopropanesulphonic acid, 5-aminovaleric acid, and guanidinoethanesulphonic acid). Local application of muscimol into the nucleus raphe dorsalis caused a dose-dependent increase in spontaneous motor activity. Muscimol-stimulated motor activity was blocked by picrotoxin. High doses relative to muscimol of 3-aminopropanesulphonic acid, guanidinoethanesulphonic acid, and 5-aminovaleric acid also attenuated the action of muscimol. Taurine by itself was ineffective on locomotion but enhanced the effect of a small dose of muscimol. Baclofen also stimulated activity but to a lesser extent than muscimol. Baclofen's stimulatory action on motor activity was partially blocked by 5-aminovaleric acid, whereas 3-aminopropanesulphonic acid was without effect. Muscimol and baclofen both increased food consumption of rats. Picrotoxin blocked this effect of muscimol, whereas the action of baclofen was blocked by 5-aminovaleric acid. Muscimol, taurine, and guanidinoethanesulphonic acid all reduced 5-hydroxytryptamine (5-HT) concentration in the hypothalamus. In radioligand binding studies, guanidinoethanesulphonic acid at micromolar concentrations displaced [ 3H]GABA from GABA A receptors. It is concluded that taurine may have a slight direct effect on GABA receptors but is more likely to act as an indirect neuromodulator of GABAergic neurotransmission in the brain.

Repeated lindane exposure in the rat results in changes in spontaneous motor activity at 2 weeks post-exposure

Male Wistar rats were given 25 doses of lindane, 10 mg/kg per day, 1 ml/kg p.o. in olive oil. or control vehicle. Two weeks after the last dose, the animals were assessed for modifications in spontaneous motor activity, plus-maze behavior, shuttle-box active avoidance acquisition, brain regional concentrations of biogenic amines and metabolites, and regional [ 35S]TBPS binding. Rats treated with lindane showed an increase in spontaneous motor activity. Although no additional behavioral or neurochemical modifications were found, the changes in activity observed at 2 weeks post-exposure further demonstrate the need to assess lor long lasting neurobehavioral sequelae of repeated lindane exposure.

Effect of peripheral administration of cinnarizine and verapamil on the abstinence syndrome in diazepam-dependent rats

The effects of two calcium channel blockers (verapamil and cinnarizine) were evaluated on diazepam withdrawal symptoms. Rats were made diazepam dependent by chronic treatment with daily injections of the drug, 20 mg/kg IP for 3 weeks. On abrupt termination of the drug, animals showed withdrawal hyperactivity that was assessed by autonomic, behavioural and motor signs. The peak effect was seen 3 days after the withdrawal of diazepam. On IP administration, verapamil and cinnarizine (10, 20 and 40 mg/kg) given on eight occasions at an interval of 12 h reversed the withdrawal-induced increase in spontaneous motor activity. Cinnarizine in higher doses (20 and 40 mg/kg) was found to be effective in suppressing the behavioural signs but verapamil did not show any protective effect against startle response and irritability. These results suggest that modulation of the calcium influx in the CNS might influence withdrawal.

Preclinical profile of the anticonvulsant remacemide and its enantiomers in the rat

Studies conducted by Fisons Pharmaceuticals and the Antiepileptic Drug Development Program (ADD Program) of the Epilepsy Branch (NINDS, NIH) revealed that ‘remacemide’ (FPL 12924, formerly PR 934-423) was effective orally in the prevention of maximal electroshock seizures (MES) in rats. In this context (−)stereoisomer (FPL 14145) was of equal potency to the racemate (remacemide), while the (+) stereoisomer (FPL 14144) was 54% less potent. With respect to neurotoxicity, remacemide and its enantiomers possessed more favorable therapeutic indices than phenobarbital and valproate and less favorable indices than phenytoin and carbamazepine. The duration of protection of rats in the MES test at the ED 50 or 3 × ED 50 of remacemide and the (+)isomer was better or on par with the best reference compounds, phenytoin and phenobarbital. After subchronic administration of either the ED 50 or the ED 97 of remacemide, no tolerance developed in the hexobarbital sleep test, however, the activities of 3 hepatic microsomal enzymes were elevated. In naive rats high doses of remacemide or its (−)isomer and low doses of phenobarbital caused an increase in spontaneous motor activity. Alternatively, motor activity was depressed subsequent to high doses of phenobarbital and phenytoin. Remacemide was inactive against pentylenetetrazol and ‘kindling’ seizures. It was without effect in 5 electrophysiological tests (evoked responses, recurrent inhibition, longterm potentiation, penicillin-induced discharge rate and veratridine-induced depolarization) employing the in vitro hippocampal slice technique. Moreover, remacemide failed to demonstrate potent binding in vitro to neuronal l-glutamate, γ-amino-butyrate A, adenosine A 1, benzodiazepine, N- methyl- d-aspartate (strychnine-insensitive glycine and ion channel subsites) or muscarinic receptors. In conclusion, remaoemide specifically prevents seizures elicited by MES, an action predicting utility in patients with generalized tonic/clonic convulsions.

Effect of Panax ginseng on age-related changes in the spontaneous motor activity and dopaminergic nervous system in the rat.

Effects of Panax ginseng on the spontaneous motor activity and central dopaminergic systems in old rats were investigated and compared with those in young rats. Oral intake of a 1.8% water extract of Panax ginseng for four weeks produced an increase in spontaneous motor activity during the dark period in old rats, while it caused a decrease in the activity in young rats. After the intake of ginseng extract for five weeks, it caused a significantly low dopamine utilization in the daytime in the striatum of old rats, while it produced a high dopamine utilization in the structure of young rats. Concentrations of striatal dopamine D-2 receptors in old rats were significantly lower than that in young rats, although subchronic Panax ginseng did not affect the striatal D-1 and D-2 receptors of old rats. These results suggest that subchronic intake of ginseng extract inhibits the activity of nigro-striatal dopamine neurons in the daytime and activates spontaneous motor activity during the dark period in old rats, while it produces opposite effects in young rats.

Effect of Panax Ginseng on Age-Related Changes in the Spontaneous Motor Activity and Dopaminergic Nervous System in the Rat

Effects of Panax ginseng on the spontaneous motor activity and central dopaminergic systems in old rats were investigated and compared with those in young rats. Oral intake of a 1.8% water extract of Panax ginseng for four weeks produced an increase in spontaneous motor activity during the dark period in old rats, while it caused a decrease in the activity in young rats. After the intake of ginseng extract for five weeks, it caused a significantly low dopamine utilization in the daytime in the striatum of old rats, while it produced a high dopamine utilization in the structure of young rats. Concentrations of striatal dopamine D-2 receptors in old rats were significantly lower than that in young rats, although subchronic Panax ginseng did not affect the striatal D-1 and D-2 receptors of old rats. These results suggest that subchronic intake of ginseng extract inhibits the activity of nigro-striatal dopamine neurons in the daytime and activates spontaneous motor activity during the dark period in old rats, while it produces opposite effects in young rats.

Cerebral glucose utilization during diazepam withdrawal in rats

The diazepam withdrawal syndrome in rats was characterized behaviorally by an increase in spontaneous motor activity, slight body tremors and a lack of convulsions. The 2-deoxyglucose (2-DG) technique was used to measured quantitatively cerebral glucose utilization during diazepam withdrawal and revealed changes in glucose utilization in 30% of the 54 structures evaluated. Areas of increased glucose utilization included medial geniculate, inferior colliculus, visual cortex, mamillary body, dorsal hippocampus, cerebellar flocculus, and zona reticulata and zona compacta of the substantia nigra. Areas of decreased glucose utilization included columnar areas in frontal sensorimotor cortex, caudate, globus pallidus, olfactory cortex, nucleus accumbens and internal capsule. There was no single or consistent relationship between reported benzodiazepine receptor densities and glucose utilization.

Novel effect of chronic corticosterone treatment on escape behavior in rats

Chronic administration of corticosterone in rats (4-35 mg/kg/day) produces a marked dose-dependent increase in the frequency of escape behavior observed when animals are held by the tail on a flat surface. The effect is fully developed after 3 days treatment. It is not the result of an increase in spontaneous motor activity since the hormone tends to reduce the latter behavior. Adrenalectomy decreases the escape behavior and tends to do so to a greater degree in rats subjected to chronic stress (restraint) than in nonstressed controls. The results suggest that endogenous corticosterone serves to maintain the above escape behavior during chronic stress.

Analysis of the nature of antagonism of the reserpine-induced hypothermia by imipramine.

Antagonism of reserpine-induced hypothermia is an animal model used in the screening of antidepressants. The activity of imipramine on this test is partly impaired by propranolol. This effect of imipramine was analyzed using specific adrenoceptor and 5-HT receptor blocking drugs in order to determine the nature of this effect of propranolol. The non-selective beta 1-beta 2 adrenoceptor antagonist, propranolol as the specific beta 1 adrenoceptor antagonist betaxolol, but not the specific beta 2 blocking drug DL-erythro-3-isopropylamino-1-(7-methyl-4-indanyloxy)-2-butanol hydrochloride 313.9 (ICI 118,551), partly antagonized the effect of imipramine at 30 min. None of the serotonin (5-HT) receptor antagonists, methysergide, metergoline, ritanserin and buspirone, impaired the effect of imipramine. On the contrary, methysergide alone antagonized reserpine-induced hypothermia and methysergide or metergoline increased the action of imipramine. Propranolol impaired neither the hypothermia induced by an agonist at the 5-HT 1A receptors: 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) nor the increase in spontaneous motor activity induced by an agonist at the 5-HT 1B receptors: 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1-H indole (Ru 24,969). It is concluded that the effect of propranolol is not the result of a blockade of 5-HT 1A, 5-HT 1B or 5-HT 2, but is in part due to blockade of beta 1 adrenoceptors.

Time-dependent neurobiological effects of colchicine administered directly into the hippocampus of rats

Rats were given bilateral injections of colchinine into the dorsal and ventral hippocampus. Behavioral, neurochemical and histopathological measurements were taken, up to 12 weeks after surgery. Colchicine produced a consistent increase in spontaneous motor activity, enhanced acoustic startle reactivity, and accelerated acquisition of two-way shuttle ☐ avoidance, but did not affect reactivity to a noxious thermal stimulus. Measurement of dynorphin in the hippocampus indicated ithat colchicine rapidly depleted this neuropeptide, which is thought to be contained preferentially in the mossy fibers of granule cells of the hippocampus. Colchicine also decreased Met-enkephalin in the hippocampus, but the magnitude of the change (22%) was less than that (89% depletion) observed for hippocampal dynorphin. Examination of hippocampal morphology using light microscopic techniques indicated that colchicine caused approximately 60% degeneration of granule cells in the hippocampus. Although the length of the pyramidal cells was decreased (12–16%), the width of the CA 1 and CA 3 region of the hippocampus was not affected. These data underscore the importance of the granule cells in the mediation of behavioral processes such as motor activity, startle reactivity and performance of shuttle ☐ avoidance.

Aporphine derivatives affect ocular function in diverse ways.

The sympathetic nervous system has been implicated in the ocular effects of several classes of dopamine receptor agonists. Two agonists of the aporphine class, (-) N-propylnorapomorphine [-)NPA) and norapomorphine (NA), were evaluated for effects on intraocular pressure (IOP) and pupil diameter (PD) in cats and normal (NL) and sympathectomized (SX) rabbits and on contractions of the cat nictitating membrane (CNM). Topically administered (-)NPA produced a monophasic IOP drop in the ipsilateral eye and a biphasic (increase, decrease) IOP response in the contralateral eye of normal rabbits. Pupil diameter increased bilaterally. In NL cats, the ipsilateral IOP and PD response to (-)NPA was biphasic (increase, decrease) and the contralateral IOP response was monophasic (increase). (-)NPA produced an increase in spontaneous motor activity (SMA) in rabbits and cats. NA lowered IOP unilaterally in NL rabbits. In SX rabbit eyes, (-)NPA lowered IOP as much as in NL eyes but with less mydriasis. NA did not lower IOP in SX rabbit eyes. Both (-)NPA and NA inhibited contractions of the CNM elicited by electrical stimulation of the pre- and post-superior cervical ganglionic nerves. (-)NPA, but not NA, inhibited contractions elicited by exogenous norepinephrine. These results suggest that aporphine derivatives produced two diametrically opposed effects on ocular function; 1) a centrally mediated effect that enhanced noradrenergic activity to elicit mydriasis, SMA and ocular hypertension, and 2) a peripherally mediated effect to produce miosis and ocular hypotension.