Depression Of Motor Activity Research Articles

Effect of Saraswatarishta in animal models of behavior despair.

Background:Saraswatarishta (SA) is a herbo-mineral formulation consisting of 18 plants some of which are Medhyarasayanas. It has been claimed to be useful in treating central nervous system disorders.Objective:To evaluate antidepressant effect of ‘Saraswatarishta’(SA) alone and in combination with imipramine and fluoxetine in animal models of depression.Materials and Methods:After obtaining IAEC permission, 144 rats (n = 36/part) were randomized into 6 groups- Group 1: Distilled water (1 mL), Group 2: Imipramine (30 mg/kg), Group 3: Fluoxetine (10 mg/kg), Group 4: SA (1.8 mL/kg), Group 5: Imipramine + SA, Group 6: Fluoxetine + SA. Effects of study drugs were evaluated in forced swim test (FST) with single exposure to FST (Part 1) and repeated exposure for 14 days (Part 2). In Part 3, reserpine was used with FST and effects of study drugs were evaluated against single exposure to FST. Same model was used with repeated exposures to FST (Part 4). In each part, rats were subjected to open field test (OFT) for 5 min prior to final FST. The variables measured: Immobility time in FST; line crossing, rearing and defecation in the OFT.Results:In all four parts, individual drugs and combinations thereof produced significant decrease in immobility time as compared to control, and extent of decrease was comparable amongst these groups. However, values for combination of fluoxetine with SA group were found to be lesser than that for individual agents in Parts 2 and 3. Combination of SA with imipramine did not enhance its anti-depressant effect in any of the parts. OFT findings did not vary significantly amongst the study groups.Conclusion:Decreased immobility in FST and absence of generalized stimulation or depression of motor activity in OFT point towards potential antidepressant effect of Saraswatarishta. Its co-administration with fluoxetine showed more promising effects.

Antipyretic effect of central [Pyr1]apelin13 on LPS-induced fever in the rat

Intracerebroventricular (i.c.v.) injections of apelins have been shown to modulate the central control of cardiovascular function, as well as the homeostasis of fluid and salt balance, and to some extent also body core temperature. Here, we investigated the effects of i.c.v. administration of [Pyr1]apelin13 (PyrAp13; 20nmol) dissolved in artificial cerebrospinal fluid (aCSF), as compared to aCSF alone, on fever and sickness behavior elicited in rats by intraperitoneal injection of bacterial lipopolysaccharide (LPS, 100μg/kg). Injections of LPS induced a short phase of hypothermia followed by a biphasic fever, depression of motor activity, anorexia and adipsia. I.c.v. injections of PyrAp13 without systemic LPS application slightly augmented motor activity at statistically unaltered core temperature. In combination with LPS, central administration of PyrAp13 significantly reduced fever during the time period of 3–9h after injection, but did not significantly attenuate anorexia and adipsia, and had no effect on LPS-induced lethargy. Rats injected with PyrAp13 along with LPS showed a reduced level of LPS-induced circulating tumor necrosis factor-α (TNF-α). Primary neuroglial cultures established from the hypothalamic paraventricular nucleus (PVN) and the median preoptic nucleus (MnPO), brain sites being of major importance for central thermoregulation and also expressing the apelin receptor, were incubated with medium alone, medium containing LPS (100μg/ml) or LPS plus PyrAp13 (10−6mol/L). Ninety minutes after start of the incubation, LPS alone but not LPS in combination with PyrAp13 (10−6mol/L) caused a significant elevation of TNF-α in the supernatants. The novel observation that PyrAp13 represents a centrally acting endogenous antipyretic peptide is discussed in relation to its capacity to modulate peripheral and central formation of TNF-α.

Pyrexia, anorexia, adipsia, and depressed motor activity in rats during systemic inflammation induced by the Toll-like receptors-2 and -6 agonists MALP-2 and FSL-1

Macrophage-activating lipopeptide-2 (MALP-2) from Mycoplasma fermentans has been identified as a pathogen-associated molecular pattern of Mycoplasmas that causes activation of the innate immune system through the activation of the heterodimeric Toll-like receptors (TLRs)-2 and -6. The aim of this study was to characterize the ability of MALP-2 and a synthetic analog fibroblast-stimulating lipopeptide-1 (FSL-1; represents the NH2-terminal sequence of a lipoprotein from M. salivarium) to act as exogenous pyrogens, to induce formation of cytokines (endogenous pyrogens), and to cause sickness behavior, such as depressed motor activity, anorexia, and adipsia. For this purpose, body temperature, activity, food intake, and water intake were recorded for 3 days by use of telemetry devices in several groups of rats treated with MALP-2/FSL-1 or the respective control solutions. Intraperitoneal injections of FSL-1 caused fever at doses of 10 or 100 microg/kg, which was preceded by a pronounced phase of hypothermia in response to a dose of 1,000 microg/kg. The maximal fever (a peak of 1.5 degrees C above baseline) was caused by the 100 microg/kg dose with almost identical responses to both MALP-2 and FSL-1. Fever was accompanied by pronounced rises of the proinflammatory cytokines TNF and IL-6 in plasma. Treatment with the TLR-2 and -6 agonists further induced a dose-dependent manifestation of anorexia and adipsia, as well as a reduction of motor activity. We could thus demonstrate that activation of TLR-2 and -6 can induce systemic inflammation in rats accompanied by the classical signs of brain-controlled illness responses.

Anandamide is able to inhibit trigeminal neurons using an in vivo model of trigeminovascular-mediated nociception.

Arachidonylethanolamide (anandamide, AEA) is believed to be the endogenous ligand of the cannabinoid CB(1) and CB(2) receptors. CB(1) receptors have been found localized on fibers in the spinal trigeminal tract and spinal trigeminal nucleus caudalis. Known behavioral effects of anandamide are antinociception, catalepsy, hypothermia, and depression of motor activity, similar to Delta(9)-tetrahydocannanbinol, the psychoactive constituent of cannabis. It may be a possible therapeutic target for migraine. In this study, we looked at the possible role of the CB(1) receptor in the trigeminovascular system, using intravital microscopy to study the effects of anandamide against various vasodilator agents. Anandamide was able to inhibit dural blood vessel dilation brought about by electrical stimulation by 50%, calcitonin gene-related peptide (CGRP) by 30%, capsaicin by 45%, and nitric oxide by 40%. CGRP(8-37) was also able to attenuate nitric oxide (NO)-induced dilation by 50%. The anandamide inhibition was reversed by the CB(1) receptor antagonist AM251. Anandamide also reduced the blood pressure changes caused by CGRP injection, this effect was not reversed by AM251. It would seem that anandamide acts both presynaptically, to prevent CGRP release from trigeminal sensory fibers, and postsynaptically to inhibit the CGRP-induced NO release in the smooth muscle of dural arteries. CB(1) receptors seem to be involved in the NO/CGRP relationship that exists in causing headache and dural blood vessel dilation. It also seems that some of the blood pressure changes caused by anandamide are mediated by a noncannabinoid receptor, as AM251 was unable to reverse these effects. It can be suggested that anandamide is tonically released to play some form of modulatory role in the trigeminovascular system.

HU-210 shows higher efficacy and potency than morphine after intrathecal administration in the mouse formalin test

The discovery of endocannabinoids opens up new perspectives in experimental pain research. Here we present data for the excellent antinociceptive properties of the synthetic cannabinoid, R(−)-7-hydroxy-delta-6-tetra-hydrocannabinol-dimethylheptyl (HU-210), after intrathecal and oral administration in mice. It is known that cannabinoids depress motor activity. Therefore, these compounds are suspected of influencing antinociceptive tests. Our behavioural tests (RotaRod, tail flick) clearly show that HU-210 affects nociceptive behaviour even at dosages which do not yet influence motor activity. Moreover, spinal microdialysis (5 μl/min) in the dorsal horn of freely moving mice showed an enhancement of prostaglandin production during the formalin test. HU-210 applied via artificial cerebral spinal fluid during microdialysis perfusion increases prostaglandin concentrations under both baseline and formalin test conditions. Indomethacin reduces the HU-210 effect on pronociceptive prostaglandin production but does not reinforce the antinociceptive properties of HU-210. Thus, HU-210 shows antinociceptive properties that are independent of its influence on the prostaglandin pathway.

Behavioral thermoregulatory response to chlorpyrifos in the rat

Chlorpyrifos (CHP) is a heavily used organophosphorous-based insecticide that elicits thermoregulatory dysfunction in the rat characterized by an initial period of hypothermia followed by a delayed hyperthermia lasting 24–72 h after exposure. The purpose of the present study was to determine (1) if the delayed hyperthermia is linked to CHP-induced hypothermia and (2) if the hypothermia and delayed hyperthermia are regulated by the CNS thermoregulatory centers. Core temperature ( T c) and motor activity (MA) of female Long-Evans rats were monitored via radiotelemetry. Rats housed in a temperature gradient were administered the control vehicle or CHP (25 mg/kg (p.o.)) while T c, MA and ambient temperature ( T a) preferred by rats in the gradient (i.e. selected T a) were recorded. There was an initial reduction in T c concomitant with a decrease in selected T a. A gradual recovery in T c occurred during the first night along with a preference for warmer T a’s and depressed MA. The day after CHP there was an elevation in T c but no change in selected T a, suggesting that the delayed rise in T c was regulated. In another experiment, the hypothermic effects of CHP (25 mg/kg (p.o.)) were blocked by raising T a from 22 to 31°C immediately after CHP administration. Non-heated rats administered CHP underwent a marked period of hypothermia followed by an elevation in diurnal T c for 2 days. Heated rats showed no hypothermic response but did undergo a hyperthermic response 48 h after CHP. MA was reduced during the first night after CHP in both non-heated and heated groups. Overall, the CHP-induced hyperthermia is not dependent on the development of hypothermia. Behavioral thermoregulatory observations suggest that both hypothermia and hyperthermia are regulated by CNS thermoregulatory centers.

Effect of gas-polluted air on the heart function indices of boys aged 8-10 with different levels of motor activity

The heart function indices of boys aged 810 living in gas-polluted air conditions and going in for sports systematically are studied. In intensified motor activity the shock and minute blood volumes increased significantly in both schools. In depressed motor activity the plausible changes of the heart function indices are found only in gas-polluted air condition.

Benzodiazepine (omega) receptor partial agonists and the acquisition of conditioned fear in mice.

It is well established that benzodiazepines can produce anterograde amnesia in humans and interfere with the acquisition of passive avoidance and spatial responses in rodents. However, the extent to which the disruption of learning is a secondary effect of the sedation produced by these drugs has not been clearly established. In order to investigate this question, the effects of several BZ (omega) receptor partial agonists were studied on the acquisition of conditioned fear (passive avoidance learning) in mice. As these drugs have been shown to produce anticonvulsant and anxiolytic-like effects without sedation or depression of motor activity, it was of interest to see whether they could disrupt learning. Clear effects on the acquisition of conditioned fear were produced by imidazenil (0.01-1.0 mg/kg), divaplon (1-60 mg/kg), ZK 91296 (3-60 mg/kg), and Ro 17-1812 (0.1-10 mg/kg). However, bretazenil (0.1-10 mg/kg) did not produce statistically significant effects. Only the high dose of imidazenil (1.0 mg/kg) decreased levels of exploratory behaviour. These results show that BZ (omega) receptor partial agonists without apparent sedative actions can disrupt fear learning, indicating that the effects of this class of drugs on passive avoidance learning can be dissociated from sedation. The reasons for the observed differences between the different compounds studied are unclear at present and may be related to differences in intrinsic activity or receptor subtype selectivity.

Repeated Injections of Interferon-α A/D in Balb/c Mice: Behavioral Effects

Interferon/α decreases food intake and activity in mice and humans. The present study further explores parallels between effects of this protein in humans and mice, using a hybrid recombinant interferon-α A/D (INF-α A/D) that has antiviral and hepatic activity in mice. Measures of activity (open field), muscle strength (forelimb grip strength), and motor ability (swim posture and endurance with 0, 3, and 6% added weight) were examined in Balb/c mice injected with 1600 U/g of hybrid rhuIFN-α A/D daily for 5 days (n = 9) or with IFN vehicle (n = 11). Open field activity was significantly depressed in the group exposed to IFN. The number of times the nose dipped under the water when swimming with 3% added body weight was higher in the IFN-treated mice, while float time was decreased with 6% added weight. The IFN-treated mice were slower to adopt the new strategies necessary to swim with added weight. Depression of motor activity is a robust, general effect of IFN treatment observed in this as well as previously published studies. Together, these studies demonstrate activity decrements in two different strains of mice, two different activity measures, acute and chronic injections, and recombinant and nonrecombinant IFN preparations.

Sedative hypnotic action of pala papua, Myristica argentea, in mice

AbstractAn aqueous extract of the seed of Myristica argentea depressed motor activity and caffeine‐induced excitement, and prolonged spontaneous and pentobarbital‐induced sleep in mice; it also inhibited brief tonic spasm caused by pentobarbital before hypnosis. These actions are discussed by comparing them with those of nutmeg essential oil, the seed essential oil of Myristica fragrans.

Ethanol-induced analgesia

The effect of ethanol (ET) on nociceptive sensitivity was evaluated using a new tail deflection response (TDR) method. The IP injection of ET (0.5 – 1.5 g/kg) produced rapid dose-dependent analgesia. Near maximal effect (97% decrease in TDR) was produced with the 1.5 g/kg dose of ET ten minutes after injection. At ninety minutes post-injection there was still significant analgesia. Depression of ET-induced nociceptive sensitivity was partially reversed by a 1 mg/kg dose of naloxone. On the other hand, morphine (0.5 or 5.0 mg/kg IP) did not modify ET-induced analgesia, while 3.0 minutes of cold water swim (known to produce non-opioid mediated analgesia) potentiated ET-induced analgesic effect. The 0.5 g/kg dose of ET by itself did not depress motor activity in an open field test, but prevented partially the depression in motor activity produced by cold water swim (CWS). Thus the potentiation by ET of the depression of the TDR produced by CWS cannot be ascribed to the depressant effects of ET on motor activity.

Adenosine receptor interactions and anxiolytics

[ 3 H]-N 6- cyclohexyladenosine and [ 3H]-1,3-diethyl-8-phenylxanthine label the A 1 subtype of adenosine receptor in brain membranes. The affinities of methylxanthines in competing for A 1 adenosine receptors parallel their potencies as locomotor stimulants. The adenosine agonist N 6-(-phenylisopropyl) adenosine is a potent locomotor depressant. Both diazepam and N 6-( l- phenylisopropyl) adenosine cause locomotor stimulation in a narrow range of subdepressant doses. Combined stimulant doses of the two agents depress motor activity, as do larger doses of either one, given separately. Evidence supporting and against the hypothesis that some of the actions of benzodiazepines are mediated via the adenosine system is reviewed. A number of compounds interact with both systems, probably because of physico-chemical similarities between adenosine and diazepam. It is concluded that of the four classic actions of benzodiazepines, the sedative and muscle relaxant (but not anxiolytic or anticonvulsant) actions could possibly be mediated by adenosine.

EEG and behavioral effects of gamma-hydroxybutyrate in the rabbit

The effects of gamma-hydroxybutyrate (GHB) upon sleep wakefulness patterns and quantified nuchal muscle activity were examined in the rabbit in a dose-response paradigm (25–1,000 mg/kg). Relative to control (saline) values, there was no facilitation of sleep onset or epileptogenic activity at any of the dosages studied. However, at the higher GHB concentrations, slow wave sleep and tonic muscle activity were enhanced and a high amplitude, slow activity was superimposed on background EEG patterns. The highest concentration of GHB (1,000 mg/kg) was associated with depression of motor activity. An enhancement of paradoxical sleep observed at lower GHB levels in other species occured in attenuated form in the rabbit. The results indicate dose-related effects on both sleep and motor activation in the rabbit, but the absence of seizure activity for the concentrations of GHB studied.

Haemolymph γ-aminobutyric acid titers in the greater wax moth, Galleria mellonella: Changes during normal or supernumerary larval development and following injury

The γ-aminobutyric acid (GABA) titers of haemolymph from wax moths, Galleria mellonella, exhibit stage specific fluctuations associated with the metomorphic moult. Maximal titers, as high as 0.9 mM, are observed during those times in development when animals are behaviorally quiescent. Injury-induced delay in metamorphosis alters the patterns of GABA titer change; it delays the appearance of the GABA peak. Brain and thoracic ganglia from last instar larvae release GABA in vitro whereas fat body and silk glands to not release GABA. The developmental changes in G. mellonella haemolymph GABA titers appear to be associated with depression of motor activity and with neurosecretory endocrine activity.

Cerebroventricular infusion in the rat: Depression of motor activity and paradoxical sleep

The effect of infusing artificial (aCSF) or natural cerebrospinal fluid (CSF) into the lateral ventricle of the rat was investigated by recording motor activity and sleep. The rate and duration of infusions was varied. Motor activity and paradoxical sleep showed a prolonged depression during the post-infusion period when the volume of the infusate was at least 45 μl.

A novel activity cage for rats: characterization of some phenylethylamine derivatives with central stimulant and depressant effects.

1. A novel activity cage for rats is described. Eight light beams are aimed at a light-conducting perspex rod at the centre of a cylindrical cage. The photoresistor at the end of the rod detects the changes in light intensity produced by interruption of the light beams. 2. The apparatus is simple to operate and was capable of detecting small differences in the motor activity of groups of rats. 3. Dose-dependent increases in motor activity were produced by dexamphetamine (1.36 to 27.3 mumol/kg, i.p.). The depressant effects produced by 20 mumol/kg doses of nonfenfluramine were greater than those of fenfluramine. Large doses (100 mumol/kg) of tranylcypromine stimulated motor activity whereas its cis-isomer, cis-2-phenylcyclopropylamine, depressed motor activity.

Behavioral suppressant effects of clonidine in strains of normotensive and hypertensive rats

The behavioral effects of orally administered clonidine were investigated in Long—Evans (LE), Sprague—Dawley (SD) or Kyoto Wistar (KW) rats assumed to be normotensive and in NIH spontaneously hypertensive (SH)_ rats. Although clonidine (0.05–1 mg/kg) resulted in the same quanlitative effects, i.e., depression of motor activity, the dose of clonidine required to depress motor activity to 50% of control levels (ED 50) tended to vary according to strain. An analysis of variance of the dose response curves for the foru strains of rats indicated a significant strain effect. When the effects of clonidine on food-reinforced operant responding were investigated, it was observed that SD and SH rats differed with regard to rate and temporal patterning of IRT > 20 sec responding. Although oral administration of clonidine (0.006–.01 mg/kg) procedure similar percentage decreases from control in SH and SD rats, an analysis of the temporal patterning of responding indicated differences in responsiveness to the behavioral effects of clonidine. These studies demonstrate strain-related differences in responsiveness to the behavioral suppressant effects of clonidine. Marked between genetically hypertensive rats and rats assumed to be normotensive were not evident.

Caffeine and chlordiazepoxide: effects on motor activity in the chronic thalamic rat.

The effects of three doses of caffeine and of chlordiazepoxide (CDX) on motor activity were tested in the chronic thalamic rat. In this preparation virtually all cortical, striatal and limbic structures were ablated. A small dose of caffeine had only a weak motor stimulant effect which was succeeded by sedation. Larger doses that are stimulatory in intact animals, depressed motor activity in the thalamic rat. Amphetamine, in contrast to caffeine, produced a substantial motor stimulation. CDX caused a dose-dependent reduction of motor activity, similar to its effect in the intact rat. It is concluded that (a) telencephalic structures are involved in mediating the stimulatory action of caffeine; (b) a sedative component of caffeine may be present, but masked, in the intact animal, and may be due to serotoninergic mechanisms; (c) the presence of limbic structures is not necessary for the sedative effect of CDX.

Comparison of acetaldehyde and ethanol: Depression of motor activity in mice

The fine and gross motor activity of mice was measured at 1-minute intervals for 15 minutes after intravenous administration of ethanol or acetaldehyde. Acetaldehyde transiently reduced both types of motor activity whereas the effects of ethanol were more prolonged. The 1-minute ED 50 values for depression of fine and gross activity by acetaldehyde are 2.2. and 2.7 mg/kg, respectively. The corresponding values for ethanol are 740 and 516 mg/kg. The differences in relative potencies became smaller as the time interval over which activity was measured increased. Thus, the potency of acetaldehyde as a depressant of behavior relative to ethanol is considerably greater than has previously been reported if effects are determined immediately after drug administration.

Muscle relaxation by drugs which stimulate sensory nerve endings—II. The effect of nicotinic agents

Nicotine, given by i.v. or right intra-atrial injection in doses of 10–40 μg/kg, depressed the “spontaneous” electrical activity and tone in both extensor and flexor muscles of cats rendered rigid by intercollicular decerebration and in intact preparations under light chloraloseurethane anaesthesia. The latent periods of this action following intra-atrial injection varied from 1 to 2 sec, indicating that it must have originated from receptors located between the right atrium and the pulmonary capillary bed. The onset of the reflex motor depression frequently coincided with the onset of the vagovagal cardiodecelerator-hypotensive response, suggesting that both effects arose from the same type of receptor. These brief latency effects were dependent on vagal afferents. After vagotomy a motor depressant effect with delayed onset was seen. Instances of differential abolition, or absence, of the effect of nicotine and phenyldiguanide under varying conditions of decerebration and anesthesia suggest that the motor depressant effect of nicotine does not arise from the pulmonary deflation receptors, responsible for the effect of phenyldiguanide, but is initiated at the pulmonary arterial baroreceptors which have earlier been implicated in the hypotensive reflex response to nicotine. The motor depressant effect of nicotine was duplicated by the quaternary nicotinic agent sebacylcholine and also by acetylcholine, and was blocked by hexamethonium, confirming the peripheral reflex nature of the effect. Neuromuscular transmission was not impaired in the doses used. Dihydro-β-erythroidine, blocking the nicotinic synapse at the Renshaw interneuron, reduced or abolished the inhibition by nicotine of the knee jerk but had little influence on the reflex motor depression, while hexamethonium had the reverse effect. Thus, Renshaw inhibition was responsible for much of the depressant action of nicotine on the knee jerk but played only a minor part in the reflex motor depression. In several experiments hexamethonium itself depressed motor activity by an as yet unexplained mechanism.