Inhibition Of Spontaneous Motor Activity Research Articles

Antidepressant effects of natural and micropropagated Bacopa monnieri (L.) plant extracts

Linn. an important medicinal plant in Indian system of alternative medicine belonging to Scrophulariaceae family. It is distributed in the wet and marshy lands throughout India, Nepal and many other parts of world. This study was carried out to evaluate the natural and micropropagated plant extract for antidepressant activity. Antidepressant effects of natural and micropropagated plant extract was evaluated by spontaneous motor activity. All the extracts were administered 30 min prior to the test. The standard drug chlorpromazine (2mg/kg) was used. The locomotor activity was performed using an actophotometer after different doses of test drug. Result: The locomotor activity of control and treated mice were recorded and statistically correlated among the control, standard and the test drugs. The inhibition of spontaneous motor activity in case of BMN, BMS extract was found 291, 93.5 and 277, 93.66 count at interval of 30 and 60 min. respectively. But in case of BMM plant extract it was found 290, 87.33 and 146 count at 30, 60 and 120 min. interval respectively so results showed that a significant antidepressant-like effect at a dose of 100 mg/kg. It can be used as adjuvant therapy for depression. There was statistically highly significant (p value <0.001) association observed. Further evaluation on the different mechanisms of action of ethanolic extracts of natural and micropropagated plant needs to be studied in the future.

Asenapine sensitization from adolescence to adulthood and its potential molecular basis

Asenapine is a new antipsychotic drug that induces a long-lasting behavioral sensitization in adult rats. The present study investigated the developmental impacts of adolescent asenapine treatment on drug sensitivity and on 3 proteins implicated in the action of antipsychotic drugs (i.e. brain-derived neurotrophic factor (BDNF), dopamine D2 receptor, and ΔFosB) in adulthood. Male adolescent Sprague–Dawley rats (postnatal days, P 43–48) were first treated with asenapine (0.05, 0.10 or 0.20mg/kg, sc) and tested in the conditioned avoidance or PCP (2.0mg/kg, sc)-induced hyperlocomotion tasks for 5 days. After they became adults (∼P 76), asenapine sensitization was assessed in a single avoidance or PCP-induced hyperlocomotion challenge test with all rats being injected with asenapine (0.10mg/kg, sc). Rats were then sacrificed 1 day later and BDNF, D2 and ΔFosB in the prefrontal cortex, striatum and hippocampus were examined using Western blotting. In adolescence, repeated asenapine treatment produced a persistent and dose-dependent inhibition of avoidance response, spontaneous motor activity and PCP-induced hyperlocomotion. In the asenapine challenge test, adult rats treated with asenapine (0.10 and 0.20mg/kg) in adolescence made significantly fewer avoidance responses and showed a stronger inhibition of spontaneous motor activity than those previously treated with saline. However, no group difference in the levels of BDNF, D2 and ΔFosB expression was found. These findings suggest that although adolescent asenapine treatment for a short period of time induces a robust behavioral sensitization that persists into adulthood, such a long-term effect is not likely to be mediated by BDNF, D2 and ΔFosB.

Electrophysiological study of infant and adult rats under acute intoxication with fluoroacetamide

A study was conducted of acute intoxication of infant and adult Wistar rats with fluoroacetamide (FAA), an inhibitor of oxidative metabolism. FAA was administered orally to adult rats at 1/2 LD(50) and subcutaneously to infant rats at LD(100) or 1/10 LD(50). Electrocardiogram (ECG), respiration and motor activity were registered for 7 days. Clinical analysis of ECG and the heart rate variability (HRV) was carried out to assess the state of the vegetative nervous system. In adult rats, FAA caused marked disturbances in the activity of cardiovascular and respiratory systems, including the development of a potentially lethal acute cor pulmonale. Conversely, there were no significant changes of cardiac function and respiration in infant rats; they died because of extreme emaciation accompanied by retardation of development. In adult rats, bursts of associated cardiac and respiratory tachyarrhythmia, as well as regular high amplitude spasmodic sighs having a deca-second rhythm were observed. In both infant and adult rats, FAA caused short-term enhancement of humoral (metabolic) and sympathetic activities, followed by a gradual and stable predominance of parasympathetic influence on HRV. Under conditions of FAA inhibition of the tricarboxylic acid cycle, the observed physiological reactions may be explained by activation of alternative metabolic pathways. This is also supported by a lack of ontogenetically caused inhibition of spontaneous motor activity in infant rats poisoned with FAA, which highlights the significance of the alternative metabolic pathways for implementation of deca-second and minute rhythms and a lack of a rigid dependence of these rhythms upon activity of neuronal networks.

Comparison of effects of khat extract and amphetamine on motor behaviors in mice

The aim of this study was to determine if the psychostimulants, khat and amphetamine, exert similar effects in two tests of motor behaviors. Dose–response relationships were obtained for khat extract and d- and l-amphetamine given to mice by the intragastric route. Head twitch responses were significantly increased by khat and amphetamines. The latter were more potent than khat; dose–response curves for amphetamines had inverted U shapes. Khat extract decreased spontaneous motor activity, as measured by a photoactometer. Effects of amphetamines in this test were more variable and subject to dose dependent reversal. Other behaviors produced by higher doses of amphetamines interfered with specific motor responses under evaluation. Pretreatment with methysergide, a serotonin antagonist, significantly blocked head twitch responses but not spontaneous activity. Conversely, pretreatment with haloperidol decanoate, a dopamine receptor antagonist, prevented inhibition of spontaneous motor activity ordinarily evoked by khat and low dose d-amphetamine. We conclude that motor effects of khat and amphetamine resemble one another, but only at certain doses. Unlike khat, amphetamine causes additional behaviors that obscure motor responses of the types examined here. Results with transmitter receptor blockers suggest that motor effects of khat, like those of amphetamine, may be modulated by serotonin and dopamine.

Glucagonlike peptide-1 (GLP-1) participation in ileal brake induced by intraluminal peptones in rat.

The aim of this study was to determine the mechanisms implicated in the gastrointestinal inhibition induced by ovoalbumin hydrolysate infused intraluminally. We studied the site of action, the possible implication of GLP-1, and the nervous mechanisms involved. We prepared anesthetized Sprague-Dawley rats with strain gauges in the antrum, duodenum, and proximal jejunum and a catheter in the duodenum or ileum for peptone infusion. Both intraduodenal (N = 6) and intraileal (N = 5) infusion of ovoalbumin hydrolysate induced inhibition of spontaneous motor activity in the antrum, duodenum, and proximal jejunum. Duodenal inhibition induced by intraduodenal (N = 6) or intraileal (N = 6) infusion of ovoalbumin hydrolysate was reversed by intraarterial infusion of GLP-1 receptor antagonist, exendin (9-39) (3 x 10(-8) mol/kg/40 min). Finally, a combination of the adrenergic blockers phentolamine and propranolol (1 mg/kg, each; N = 7) completely blocked inhibitory gastrointestinal motor actions caused by intraduodenal infusion of ovoalbumin hydrolysate. This study demonstrates that peptone, intraluminally infused, participates in the regulation of gastrointestinal motility through stimulation of adrenergic pathways in anaesthetized rats. Moreover, these effects are partly mediated by GLP-1 secretion. The ileum seems to be the site of action, indicating a role of GLP-1 on the ileal break mechanism.

Sympathetic pathways mediate GLP-1 actions in the gastrointestinal tract of the rat

The aim of this study was to establish the actions of GLP-1 (7-37) on gastrointestinal motility in rats. We prepared anaesthetized Sprague-Dawley rats with strain-gauges in the antrum, duodenum and the proximal jejunum and a catheter in the aorta close to the coeliac artery for close infusion of substances. Intraarterial GLP-1 infusions (3×10 −10 and 3×10 −9 moles/kg per 10 min) ( n=8) induced inhibition of spontaneous motor activity in the antrum, duodenum and proximal jejunum. Inhibition induced by GLP-1 was reversed by i.v. infusion of GLP-1 receptor antagonist, Exendin (9-39) (3×10 −8 moles/kg per 10 min) ( n=6). Neither the presence of l-NNA (10 −5 moles/kg) ( n=9) nor the VIP receptor antagonist [4-Cl-D-Phe 6, Leu 17 ]-VIP (3×10 −8 moles/kg per 10 min) ( n=8) modified responses to GLP-1. However, a combination of the adrenergic blockers phentolamine and propranolol (1 mg/kg each) ( n=8) completely blocked motor actions of GLP-1 in all the organs studied. Moreover, inhibition of gastrointestinal motor activity by GLP-1 was blocked by previous infusion of hexamethonium (10 mg/kg) ( n=4). This study demonstrates that GLP-1 inhibits gastrointestinal motor activity of the rat acting on specific GLP-1 receptors and via stimulation of adrenergic pathways.

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.

Selective antagonism of acute ethanol-induced motor disturbances by centrally administered Ro 15-4513 in mice

Results of the present investigation demonstrated that Ro 15-4513 when given ICV selectively antagonized ethanol-induced motor distrubances at doses that did not produce motor incoordination and lacked proconvulsant activity. Ro 15-4513 in 10-, 15-, and 22-ng doses antagonized, roughly in a dose-dependent manner, ethanol-induced motor incoordination. The 10-ng dose produced an optimal effect with nearly complete antagonism within 30 min postethanol. The higher, 15 and 22 ng, doses of Ro 15-4513 antagonized, as well as probably reversed, ethanol-induced motor incoordination. The stimulation and inhibition of spontaneous motor activity by 1 and 2 g/kg IP ethanol, respectively, were also selectively antagonized by Ro 15-4513. Neither an alteration in the latency and/or duration of pentylenetetrazol-induced convulsions nor an antagonism to sodium pentobarbital-induced motor incoordination and inhibition of spontaneous motor activity by Ro 15-4513 at dose levels that showed antiethanol effects were observed. Only the 150-ng dose of Ro 15-4513, which exhibited intrinsic activity as proconvulsant, attenuated sodium pentobarbital-induced motor incoordination. When given alone at doses higher than those used in motor coordination experiments, Ro 15-4513 markedly increased spontaneous motor activity dose dependently.

Exaggeration of the cholecystokinin-induced motor response in the cat gastrointestinal tract.

A stimulation of distal colonic motor activity was produced in anesthetized cats following intravenous administration of cholecystokinin. The contractile response elicited by cholecystokinin was not reduced following pretreatment with atropine. However, when animals were treated with agents which increased the net cholinergic input to the colon, a marked exaggeration of the subsequent cholecystokinin-induced response occurred. This cholinergically mediated exaggeration was produced following administration of the cholinergic agonist bethanechol, or after removal of tonic inhibitory systems mediated by prostaglandin or alpha-adrenergic input, whose blockade results in atropine-sensitive colonic stimulation. Cholecystokinin was also found to produce stimulation of motor activity in the pylorus, jejunum, proximal colon and gallbladder. Cholinergically mediated exaggeration of the cholecystokinin response was also present in the pylorus and proximal colon, but not gallbladder or jejunum. An inhibition of spontaneous motor activity was produced in the ileum or duodenum following cholecystokinin administration.

Mediation of acute ethanol-induced motor disturbances by cerebellar adenosine in rats.

The possible involvement of brain adenosine in acute ethanol-induced motor incoordination (MI) and inhibition of spontaneous motor activity (SMA) was investigated in male Sprague-Dawley rats. Pretreatment with theophylline or 7-(2-chloroethyl)-theophylline, adenosine antagonists, markedly reduced ethanol-induced MI and inhibition of SMA during a 60 min test period compared with saline + ethanol group. On the contrary, pretreatment with (-)-N6(R-phenylisopropyl)adenosine (R-PIA), an adenosine agonist, or dilazep, an adenosine uptake blocker, markedly potentiated the ethanol-induced MI as well as inhibition of SMA in a 60 min test period compared with saline + ethanol group. No effect on motor coordination was seen when the drug pretreatment was not followed by ethanol. However, the adenosine agonists and antagonists did alter SMA when the pretreatment with these drugs was not followed by ethanol. Ethanol clearance was not altered by the drug pretreatment as blood ethanol levels were similar in all groups except for lower ethanol levels in the R-PIA-treated group. Adenosine A1 binding studies, using 3H-R-PIA as the radioligand and crude membrane preparation from cerebellar cortex, revealed an increase in Bmax with no significant change in Kd in ethanol-treated animals vs. saline control. Theophylline pretreatment prevented the increase in Bmax elicited by ethanol. Collectively, the data suggest that endogenous cerebellar adenosine may be a participating factor in ethanol-induced motor dysfunctions.

Giant migrating contractions and their myoelectric correlates in the small intestine.

We investigated the characteristics of spontaneously and pharmacologically induced giant migrating contractions (GMC) in the small intestine of conscious dogs. Myoelectric and contractile activities were recorded from eight sites, 40-70 cm apart, by surgically implanted bipolar electrodes and strain-gauge transducers, respectively. In addition to the usual phasic contractions in the fasted state, we observed spontaneous GMCs that generally originated in the mid or distal small intestine and migrated caudad. These contractions occurred infrequently and irregularly. The amplitude and duration of these giant contractions were severalfold larger than those of usual phasic contractions during phase III activity. The giant contractions migrated caudad at a velocity of approximately 1 cm/s. These contractions were preceded and followed by a period of inhibition of spontaneous motor activity. Some dogs whined and showed restlessness when giant contractions originated in the mid to upper small intestine. Intravenous morphine at 20, 50, 100, and 200 micrograms.kg-1 .h-1 or gastric instillation of 100 ml of 60% vinegar solution also initiated GMCs whose characteristics were similar to those of spontaneous GMCs. The GMC in response to these stimuli originated at more proximal sites than the spontaneous giant contractions. The GMC in response to morphine infusions occurred repeatedly, but in response to vinegar they occurred only once as a burst of contractions. These agents did not induce GMCs in the fed state. In most cases, the upstroke of a giant contraction was associated with a brief burst of electrical response activity. In some cases the burst of response activity lasted for the entire duration of giant contractions.

Central actions of Ganoderma lucidum

AbstractAn aqueous extract of the dried fruit bodies of Ganoderma lucidum exhibited central depressant actions as shown by the inhibition of spontaneous motor activity, analgesic activity and delay in the time to death induced by either strychnine or caffeine. The extract also elicited some muscle relaxant effects.

Pharmacological studies on ginger. I. Pharmacological actions of pungent constitutents, (6)-gingerol and (6)-shogaol.

General pharmacological studies were performed on (6)-gingerol and (6)-shogaol which are the pungent constituents of ginger (Zingiber officinale Roscoe). Intravenous (i.v.) administration of (6)-gingerol (at 1.75-3.5 mg/kg) or (6)-shogaol (at 1.75-3.5 mg/kg) and oral administration of them (at 70-140 mg/kg) produced an inhibition of spontaneous motor activity, an antipyretic and analgesic effects, prolonged hexobarbital-induced sleeping time, and these effects of (6)-shogaol were mostly more intensive than that of (6)-gingerol. (6)-Shogaol showed an intense antitussive effect in comparison with dihydrocodeine phosphate. In the electro-encephalogram of cortex, the low amplitude fast wave pattern was observed for 5 min after i.v. administration of (6)-shogaol, and then changed to the drowsy pattern, which was restored after 60 min. In the gastro-intestinal system, (6)-shogaol intensively inhibited the traverse of charcoal meal through the intestine in contrast with (6)-gingerol after i.v. administration of 3.5 mg/kg, but (6)-shogaol facilitated such an intestinal function after oral administration of 35 mg/kg. Both (6)-shogaol and (6)-gingerol suppressed gastric contraction in situ, and the suppression by the former was more intensive than that by the latter. In the cardiovascular system, both (6)-shogaol and (6)-gingerol produced depressor response at lower doses on the blood pressure. At high doses, both drugs produced three phase pattern.

The pharmacology of a new potent, long acting neuroleptic, piflutixol.

Piflutixol, 6-fluoro-9-[3-(4-(2-hydroxyethyl)piperidino)propylidene]-2-trifluoromethyl-thioxanthene, has been shown to have pronounced neuroleptic properties. It is a very potent inhibitor of methylphenidate-induced stereotypies in mice, amphetamine and apomorphine-induced stereotypies in rats, apomorphine-induced stereotypies and vomiting in dogs. Furthermore piflutixol causes cataleptic reaction in small doses and inhibits conditioned avoidance reaction in rats. The compound is equally potent orally and parenterally and has a prolonged effect. Piflutixol has up to the present proved to be the most potent inhibitor of dopamine-stimulated adenylate cyclase in rat striatum in vitro. Piflutixol has a stron sedative effect (inhibition of spontaneous motor activity, induction of ptosis and potentiation of barbiturate anaesthesia) and in addition inhibits reticular arousal reaction in very low doses. Thus piflutixol constitutes a unique combination of potent anti-stereotyped activity with potent sedative effects. This means that piflutixol may prove to be a low-dose basic neuroleptic with long duration of action.

Contribution of the metabolite 7-hydroxy-Δ 1-tetrahydrocannabinol towards the pharmacological activity of Δ 1tetrahydrocannabinol in mice

Tritium-labelled 7-hydroxy-Δ 1-tetrahydrocannabinol ( 3H-7-hydroxy-Δ 1-THC, specific activity 571 Ci/mmole) was prepared from 3H-Δ 1-THC by oxidation with a rat liver microsome preparation. Brain levels of 7-hydroxy-Δ 1-THC and Δ 1-THC in mice were measured 20 min after intravenous injection of either Δ 1-THC (2.0, 1.0 and 0.5 mg/kg) or 7-hydroxy-Δ 1-THC (1.0, 0.5 and 0.25 mg/kg) and correlated with the inhibition of spontaneous motor activity. A theoretical dose-response relationship for Δ 1-THC in the absence of the metabolite was derived on the assumption of additivity of the behavioural effects due to Δ 1THC and 7-hydroxy-Δ 1-THC present together in the mouse brain. The theoretical dose-response line for Δ 1THC and that obtained experimentally for 7-hydroxy-Δ 1-THC were parallel; on the basis of brain concentrations, 7-hydroxy-Δ 1-THC was found to be more potent than Δ 1-THC in producing behavioural changes and the calculated equipotent molar ratio was 7.1. The ratio of the concentrations of Δ 1THC and 7-hydroxy-Δ 1-THC in the mouse brain 20 min after intravenous injection of Δ 1-THC was 5.3 and the contribution of the metabolite to the overall behavioural effect was calculated as 55–63 per cent. Although metabolites of 7-hydroxyΔ 1-THC accounted for only about 10 per cent of the radioactivity present in the mouse brain 20 min after intravenous injection of 3H-7-hydroxy-Δ 1-THC, about 50 per cent of the radioactivity in the blood was present as a chromatographically more mobile material which has not yet been identified.

Brain levels of Δ 1-tetrahydrocannabinol and its metabolites in mice—correlation with behaviour, and the effect of the metabolic inhibitors SKF 525A and piperonyl butoxide

Brain levels of Δ 1-tetrahydrocannabinol (Δ 1-THC) and its major metabolite (7-hydroxy-Δ 1-THC) following intravenous injection of tritium-labelled Δ 1-THC into mice were measured and correlated with inhibition of spontaneous motor activity. Metabolism of Δ 1-THC to 7-hydroxy-Δ 1-THC was fast and both substances rapidly penetrated the C.N.S. Peak brain levels of both compounds occurred within 20 min of injection and the correlation between pharmacological response and brain concentration of either compound was equally good. Twenty min after injection more than 50 per cent of the radioactivity in blood was irreversibly bound, whereas only 12 per cent of the activity in brain was unextractable. SKF 525A (25 mg/kg i.p.) produced only a slight increase in the brain level of Δ 1-THC but the level of 7-hydroxy-Δ 1-THC was increased nearly three-fold, presumably due to the inhibition of subsequent metabolic reactions. Piperonyl butoxide (100 mg/kg i.p.) produced an increase in the brain level of Δ 1-THC but no change in the level of 7-hydroxy-Δ 1-THC. Higher doses of either inhibitor produced behavioural changes in the absence of Δ 1-THC. It is concluded that 7-hydroxy-Δ 1-THC is centrally active, but that it has not yet been demonstrated that the effects of injected Δ 1-THC are due solely to its primary metabolite.

Esters of Bicyclic Aminoalcohols II : The Synthesis of the Hydroxyquinolizidines and Some of Their Esters as Potential Therapeutic Agents

Synthesis of esters of 1- and 3-hydroxyquinolizidine as well as of the parent aminoalcohols is described, and preliminary screening suggests that antispasmodic activity is enhanced by the beta-arrangement. Suitable esters of all three aminoalcohols have also been synthesized to determine the degree of local anesthetic activity associated with them. A significant degree of inhibition of spontaneous motor activity in rats was noted with the trimethoxybenzoates of 1- and 3-hydroxyquinolizidine.