Reserpine In Rats Research Articles

EFFECTS OF RESERPINE IN RATS PRETREATED WITH ALPHA-METHYLDOPA.

EFFECTS OF RESERPINE IN RATS PRETREATED WITH ALPHA-METHYLDOPA.

Effect of imipramine, amitriptyline and their monomethyl derivatives on reserpine activity.

Abstract Impramine, amitriptyline and their respective N-monomethyl derivatives (desmethylimipramine and desmethylamitriptyline) prevent reserpine activity to varying degrees. Desmethylimipramine and desmethylamitriptyline are more effective than are imipramine and amitriptyline in reducing the hypothermia induced by reserpine in rats. Imipramine and desmethylimipramine are more effective than are amitriptyline and desmethylamitriptyline in decreasing the severity of gastric ulcers induced by reserpine in restrained rats. Desmethylimipramine does not prevent the lowering of brain amines by reserpine. The antagonistic effect of imipramine toward leptazol convulsions in mice is not shared by desmethylimipramine. Imipramine and desmethylimpramine do not potentiate the central effects of 5-hydroxy- tryptophan and tryptamine and do not prevent the hypothermia induced by 5-hydroxytryptamine, α-methyl-dopa or chlorpromazine. The activity of desmethylimipramine may be differentiated therefore on a pharmacological basis from that of the monoamine oxidase inhibitors and amphetamine.

Valeriana officinalis ameliorates vacuous chewing movements induced by reserpine in rats

Oral movements are associated with important neuropathologies as Parkinson's disease and tardive dyskinesia. However, until this time, there has been no known efficacious treatment, without side effects, for these disorders. Thus, the aim of the present study was to investigate the possible preventive effects of V. officinalis, a phytotherapic that has GABAergic and antioxidant properties, in vacuous chewing movements (VCMs) induced by reserpine in rats. Adult male rats were treated with reserpine (1mg/kg, s.c.) and/or with V. officinalis (in the drinking water, starting 15days before the administration of the reserpine). VCMs, locomotor activity and oxidative stress measurements were evaluated. Furthermore, we carried out the identification of valeric acid and gallic acid by HPLC in the V. officinalis tincture. Our findings demonstrated that reserpine caused a marked increase on VCMs and the co-treatment with V. officinalis was able to reduce the intensity of VCM. Reserpine did not induce oxidative stress in cerebral structures (cortex, hippocampus, striatum and substantia nigra). However, a significant positive correlation between DCF-oxidation (an estimation of oxidative stress) in the cortex and VCMs (p<0.05) was observed. Moreover, a negative correlation between Na(+)K(+)-ATPase activity in substantia nigra and the number of VCMs was observed (p<0.05). In conclusion, V. officinalis had behavioral protective effect against reserpine-induced VCMs in rats; however, the exact mechanisms that contributed to this effect have not been completely understood.

N-Oleoyl-Dopamine Decreases Muscle Rigidity Induced by Reserpine in Rats

N-oleoyl-dopamine (OLDA), a product of condensation of oleic acid and dopamine (DA), is a bioactive compound that crosses the blood-brain barrier after systemic administration. The possibility arises that OLDA could have a potential role in treating DA-related disorders, such as Parkinsons disease (PD). In the present study we seek to determine whether OLDA would affect muscle tone and akinesia in two rat models of PD: the reserpine-evoked muscle rigidity and the reserpine- and haloperidol-induced catalepsy. We found that OLDA (20 mg/kg) significantly decreased muscle rigidity induced by reserpine (2.5 mg/kg), measured as an increased mechanical muscle resistance (MMG) in response to a passive extension and flexion of a rat hind limb at the ankle joint. Moreover, OLDA potently decreased the reserpine-enhanced tonic and reflex electromyographic (EMG) activities recorded before and during the movement, respectively. A lower dose of OLDA (10 mg/kg) failed to have appreciable effects. The reference compound L-DOPA (25 mg/kg) also attenuated the reserpine-increased MMG and EMG activities; the effects were, however, observed much later and were less prominent than those characteristic of OLDA. In contrast to the effects on muscle tone, OLDA (20 and 40 mg/kg) did not influence catalepsy induced by either reserpine (1.25 mg/kg) or haloperidol (0.5 mg/kg). In conclusion, the study demonstrates a novel biological action of N-oleoyl-dopamine consisting of lowering the reserpine-induced muscle rigidity. However, the lack of influence on akinesia suggests that the compound has myorelaxant rather than anti-Parkinsonian properties.

Memory impairment induced by low doses of reserpine in rats: Possible relationship with emotional processing deficits in Parkinson disease

We have recently verified that the monoamine-depleting drug reserpine — at doses that do not modify motor function — impairs memory in a rodent model of aversive discrimination. In this study, the effects of reserpine (0.1–0.5 mg/kg) on the performance of rats in object recognition, spatial working memory (spontaneous alternation) and emotional memory (contextual freezing conditioning) tasks were investigated. While object recognition and spontaneous alternation behavior were not affected by reserpine treatment, contextual fear conditioning was impaired. Together with previous studies, these results suggest that low doses of reserpine would preferentially induce deficits in tasks involved with emotional contexts. Possible relationships with cognitive and emotional processing deficits in Parkinson disease are discussed.

The hypolipidemic and antiatherosclerotic activity of sympatholytic reserpine: the experimental data

The aim of this study is to detect and investigate the hypolipidemic and antiatherosclerotic activity of sympatholytic reserpine in rats, guinea pigs and rabbits. The experiments are based on the models of dislipoproteinemia and atherosclerosis. It is shown, that reserpine (in dose 0,1 mg/kg i.p.) significantly reduces dislipoproteinemia and atherosclerosis in comparison to the lipid lowing effects of fibrates.

Antagonistic interaction between adenosine A2A and dopamine D2 receptors modulates the social recognition memory in reserpine-treated rats

Increasing evidence suggests that antagonistic interactions between specific subtypes of adenosine and dopamine receptors in the basal ganglia are involved in the control of motor activity. However, there are few studies investigating this interaction in other brain regions and its role in additional functions. In the present study, we evaluated whether reserpine-treated rats (1.0 mg/kg, i.p.) exhibit altered social recognition memory abilities. The effects of acute administration of the dopamine receptor agonists 7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3 benzazepine (SKF 38393, dopamine D(1) receptor agonist) and quinpirole (dopamine D(2) receptor agonist), together with the adenosine receptor antagonists caffeine (non-selective), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, adenosine A(1) receptor antagonist) and 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-yl-amino]ethyl)phenol (ZM241385, adenosine A(2A) receptor antagonist), were also investigated. Twenty-four hours after treatment, reserpine-treated rats exhibited a significant disruption in the ability to recognize a juvenile rat after a short period of time. These animals did not show any motor deficit. The social recognition disruption induced by reserpine was reversed by acute treatment with quinpirole (0.05-0.1 mg/kg, i.p.), caffeine (10.0-30.0 mg/kg, i.p.) or ZM241385 (0.5-1.0 mg/kg, i.p.), but not with SKF 38393 (0.5-3.0 mg/kg, i.p.) or DPCPX (0.5-3.0 mg/kg, i.p.). Moreover, a synergistic response was observed following the co-administration of 'non-effective' doses of ZM241385 (0.1 mg/kg, i.p.) and quinpirole (0.01 mg/kg, i.p.). These results reinforce and extend the notion of antagonistic interactions between adenosine and dopamine receptors, and demonstrate, for the first time, that the blockade of adenosine A(2A) receptors and the activation of dopamine D(2) receptors can reverse the social recognition deficits induced by reserpine in rats.

Antiulcerogenic activity of a crude hydroalcoholic extract and coumarin isolated from Mikania laevigata Schultz Bip

The leaves of Mikania (Asteraceae) species are used in folk medicine as antispasmodic, antiulcerogenic and antirheumatic agents. Phytochemical screening of the crude hydroalcoholic 70% extract (CHE) of Mikania laevigata Shultz Bip. revealed coumarins, terpenes and organic acids. Antiulcerogenic activity of CHE was evaluated, employing different experimental models in rats, to discern the pharmacological mechanism of action. Both the antisecretory and the cytoprotection hypothesis were evaluated. The crude hydroalcoholic extract (1000 mg/kg body wt., vo) decreased the ulcerative lesion index produced by indomethacin, ethanol, stress and reserpine in rats by 85%, 93%, 82% and 50%, respectively. In the pyloric ligation model, a decrease of hydrogenionic concentration (53%) was observed, suggesting that the pharmacological mechanism has a relationship to antisecretory activity. The antisecretory mechanisms of CHE and the coumarin isolated from M. laevigata were confirmed by acid hypersecretion induced by histamine, pentagastrin and bethanechol. Duodenal administration of CHE (1000 mg/kg body wt.) and coumarin (100 mg/kg body wt.) inhibited only the gastric acid secretion produced by bethanecol. These results suggest that both CHE and coumarin may influence the secretion control mediated by the parasympathetic system.

Alpha-1 adrenoceptor up-regulation induced by prazosin but not KMD-3213 or reserpine in rats.

1. We have investigated the effects of chronic administration of prazosin (a subtype-nonspecific alpha-1 AR antagonist), KMD-3213 (an alpha-1A AR subtype-specific antagonist) and reserpine (a catecholamine depletor) on the density of alpha-1 AR subtypes in various rat tissues (liver, kidney, submaxillary gland, heart and spleen). 2. Administration of prazosin (2 mg kg(-1) day(-1), i.p.) for 2 weeks did not affect K(D) values for [(3)H]-prazosin or [(3)H]-KMD-3213 of alpha-1 ARs in five rat tissues tested. However, it caused 52% up-regulation of alpha-1B AR in the spleen, and 84% and 107% up-regulation of alpha-1A- and alpha-1B ARs, respectively, in the heart. Although major subtypes of alpha-1 AR are alpha-1A AR in the submaxillary gland, alpha-1B AR in the liver, and alpha-1A and alpha-1B ARs in the kidney, these tissues showed no up-regulation. The mRNA levels of alpha-1 AR subtypes were not affected by prazosin administration in any tissue tested. 3. Neither administration of KMD-3213 (2 mg kg(-1) day(-1), i.p.) nor reserpine (0.5 - 1 mg kg(-1) day(-1), i.p.) for 2 weeks caused any change in either the binding affinity for [(3)H]-prazosin or [(3)H]-KMD-3213 or the density of the alpha-1 AR subtypes in the five rat tissues. 4. Neither prazosin nor KMD-3213 treatment reduced the noradrenaline content in the five rat tissues, in contrast to reserpine treatment, which markedly reduced it. 5. The findings of the present study demonstrated that up-regulation of alpha-1 AR is selectively caused by prazosin treatment in some tissues but neither by KMD-3213 treatment nor by chemical denervation with reserpine. These results suggest that up-regulation of alpha-1 ARs is not caused by a simple blockade of sympathetic tone.

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An ethanolic extract of the leaves of Cissampelos sympodialis Eichl. (Menispermaceae) was found to potentiate the toxicity of pentylenetetrazol in mice. Similar to imipramine, the extract also reduced the immobility period in the forced swimming test in mice and reversed the degree of ptosis and catalepsy induced by reserpine in rats. These results suggest that the extract possesses antidepressant activity and the reported phosphodiesterase inhibitory activity of the plant may account for the observed antidepressant effect.

Antiulcerogenic activity of crude hydroalcoholic extract of Rosmarinus officinalis L.

Rosmarinus officinalis L. crude hydroalcoholic (70%) extract was evaluated for antiulcerogenic activity employing different experimental models. The crude hydroalcoholic extract (CHE) decreased the ulcerative lesion index produced by indomethacin, ethanol and reserpine in rats. No antisecretory activity was observed on pyloric ligation model. The previous administration of l-NAME, a NO-synthase inhibitor , did not reduce the antiulcerogenic activity of CHE in ethanol induced ulcer model, suggesting that the pharmacological mechanism has no relationship with nitric oxide (NO). Whereas when the animal groups were treated with indomethacin, using the same experimental model, CHE did not reduce the antiulcerogenic activity, suggesting that the pharmacological mechanism has no relationship with prostaglandins. The previous treatment with N-ethymaleimide, a thiol blocker, including mucosal nonprotein sulfhydryl groups, reduced the anitulcerogenic activity of CHE on ethanol induced ulcer model. This result suggests that the crude hydroalcoholic extract of R. officinalis L. has active substances that increase the mucosal nonprotein sulfhydryl groups content. In another hypothesis, the pharmacological mechanism could be attributed to the activity of antioxidant compounds found in the crude hydroalcoholic extract which can react with N-ethylmaleimide.

Antidepressant effect of an ethanolic extract of the leaves of Cissampelos sympodialis in rats and mice

An ethanolic extract of the leaves of Cissampelos sympodialis Eichl. (Menispermaceae) was found to potentiate the toxicity of pentylenetetrazol in mice. Similar to imipramine, the extract also reduced the immobility period in the forced swimming test in mice and reversed the degree of ptosis and catalepsy induced by reserpine in rats. These results suggest that the extract possesses antidepressant activity and the reported phosphodiesterase inhibitory activity of the plant may account for the observed antidepressant effect.

Comparative pharmacology of dothiepin, its metabolites, and other antidepressant drugs

AbstractThe pharmacology of dothiepin and its human metabolites, northiaden, dothiepin sulfoxide, and northiaden sulfoxide, has been studied to determine whether the latter contribute to the therapeutic or side effects profile of the parent tricyclic antidepressant. In vitro, dothiepin was a potent noradrenaline and 5‐hydroxytryptamine (5‐HT) uptake inhibitor, while its secondary amine metabolite, northiaden, was selective for noradrenaline. However, the sulfoxide metabolites were almost inactive as uptake inhibitors. Dothiepin and northiaden prevented the ptosis produced by tetrabenazine in mice and reserpine in rats and increased the mobility of mice in the Porsolt test. After repeated administration, both drugs decreased β‐adrenoceptor number and stimulation of the receptor‐linked adenylate cyclase by noradrenaline. Dothiepin had a higher affinity than northiaden for histamine H1, muscarinic and various adrenergic and 5‐HT receptors in vitro, whereas the sulfoxide metabolites were inactive. Overall, the data indicate northiaden almost certainly contributes to the therapeutic actions of dothiepin, but the sulfoxide metabolites do not. However, the latter are also unlikely to produce any side effects. A comparison of dothiepin with other tricyclics revealed important divergences in the profiles of uptake inhibition and receptor affinity. Thus, dothiepin is generally similar to imipramine in its pharmacology, but it differs considerably from amitriptyline and doxepin. © 1992 Wiley‐Liss, Inc.

Pharmacological characteristics of tremor, rigidity and hypokinesia induced by reserpine in rat.

The experiments characterized the dose- and time-dependence of parkinsonian motor signs induced by reserpine in rats and a standardized system of manipulation of animals, evaluation of symptoms and analysis of data was devised. The assay procedure yielded no more than 0.5, 4.5 and 0.0% false positives with the evaluation of tremor, rigidity and hypokinesia, respectively. A dose-dependent and often complete blockade of all three signs was obtained with L-DOPA plus carbidopa (10:1) as well as with other classes of pharmacological agents that are used in the treatment of Parkinson's disease, i.e. direct or indirect dopamine (DA) agonists (amantadine, pergolide, lisuride) and inhibitors of monoamine oxidase (MAO) (clorgyline, pargyline, deprenyl, tranylcypromine). The inhibitor of the uptake of DA, nomifensine, and anticholinergics, 5-hydroxytryptamine (5-HT) antagonists, histamine antagonists and tricyclic antidepressants exerted little or no effect. The effects of putative agonists and antagonists at alpha 1- and alpha 2-adrenoceptors were also examined. Yohimbine blocked tremor and rigidity, but not hypokinesia, at 0.66 and 0.28 mg/kg, respectively. It is suggested that alpha-adrenergic mechanisms and, in particular, alpha 2-adrenoceptors, may be involved in reserpine-induced tremor and rigidity. Noradrenergic and dopaminergic systems can conceivably interact to progressively generate these different motor signs.

Effect of a low-dose endotoxin pretreatment on the gastric mucosal damage induced by aspirin, phenylbutazone and reserpine in rats

The effect of endotoxin pretreatment (1 mg/kg body weight, i.p., once daily for 2 days) on the gastric mucosal damage induced by aspirin, phenylbutazone and reserpine has been studied in albino rats. When given alone, endotoxin did not produce any visibly discernible gastric lesions. It produced a significant augmentation of the gastric lesions produced by phenylbutazone and reserpine but did not significantly alter the ulcerogenicity of aspirin. The involvement of endogenous histamine formation and its release following phenylbutazone and reserpine administration and also in response to endotoxin pretreatment may be reponsible for the exacerbation of gastric lesions induced by these drugs. Recent reports indicate the involvement of endorphins and platelet activating factor (PAF) in the ulcerogenic activity of endotoxin when used in high doses and their role in the potentiation of phenylbutazone- and reserpine-induced gastric lesions has to be worked out.

Pharmacological studies of water extract of the Zizyphus seed and the Zizyphus seed containing drug

1. The pharmacological properties of a water extract of the Zizyphus seed (HO2) and that of the Zizyphus seed containing drug (HO1) were studied. 2. After oral or intraduodenal administration of 3 g/kg of HO1 or HO2, the hypnotic effects induced by hexobarbital-Na (38 mg/kg, i.p.) and diazepam-induced sleep in mice were potentiated. 3. After oral or intraduodenal administration of 3 g/kg of HO1 or HO2, gastric juice secretion and ulcers induced by water immersion stress, histamine and reserpine in rats were inhibited.

Effect of nicotine and alcohol pretreatment on the gastric mucosal damage induced by aspirin, phenylbutazone, and reserpine in rats.

The effect of nicotine and alcohol pretreatment by feeding nicotine (2.5 mg/100 ml), alcohol (25%, v/v) and their combination (nicotine 2.5 mg/100 ml + alcohol 25%, v/v) in drinking water ad libitum for 21 days was studied on the gastric mucosal damage induced by aspirin, phenylbutazone, and reserpine in rats. When given alone, neither nicotine nor alcohol produced any visibly discernible gastric lesions. Their concurrent administration, however, produced minor injury to the gastric mucosa appearing as 5-7 circular ulcers of less than 1 mm in diameter. Pretreatment with nicotine, alcohol, and their combination resulted in the significant augmentation of gastric ulcers produced by aspirin, phenylbutazone, and reserpine. The augmentation of gastric lesions in the group pretreated with the combination of nicotine and alcohol was significantly greater than in the groups treated by either of them alone. The effect of nicotine on the mucus neck cell population of the gastric mucosa and pancreatic bicarbonate secretion, and the gastric mucosal damaging effect of chronic alcohol treatment may be responsible for the potentiation of ulcerogenic effects of aspirin, phenylbutazone, and reserpine.

O-144 - Formation of gastric mucosal erosions and spectrophotometrical estimation of mucosal ischemia and congestion induced by indomethacin and reserpine in rats

O-144 - Formation of gastric mucosal erosions and spectrophotometrical estimation of mucosal ischemia and congestion induced by indomethacin and reserpine in rats

Effect of nicotine and caffeine pretreatment on the gastric mucosal damage induced by aspirin, phenylbutazone, and reserpine in rats

The effect of nicotine and caffeine pretreatment by feeding nicotine (2.5 mg %), caffeine (30 mg % base), and their combination (nicotine 2.5 mg % + caffeine 30 mg %) in drinking water ad libitum for 21 days was studied on the gastric mucosal damage induced by aspirin, phenylbutazone, and reserpine in rats. When given alone, neither nicotine nor caffeine produced any visibly discernible gastric lesions. Their concurrent administration too, did not produce any gastric mucosal injury. Pretreatment with nicotine, caffeine, and their combination resulted in significant augmentation of gastric ulcers produced by aspirin, phenylbutazone, and reserpine. However, caffeine administration produced a comparatively less profound augmentation of experimentally induced gastric lesions than that produced by nicotine pretreatment. The enhancement of gastric ulcers in the groups pretreated with the combination of nicotine and caffeine followed by one of the drugs was significantly greater than in the groups treated by either of them alone. The effect of nicotine on the mucus neck cell population of the gastric mucosa and on pancreatic bicarbonate secretion and the gastric secretory effect of caffeine may be responsible for the potentiation of the ulcerogenic effects of aspirin, phenylbutazone, and reserpine.

Effect of Nicotine, Alcohol and Caffeine Pretreatment on the Gastric Mucosal Damage Induced by Aspirin, Phenylbutazone and Reserpine in Rats

The effects of nicotine (2.5 mg/100 ml), alcohol (25% v/v) and caffeine (30 mg/100 ml base) and their combination (nicotine, 2.5 mg/100 ml; alcohol, 25% v/v; and caffeine, 30 mg/100 ml base) fed in drinking water ad libitum for 21 days were studied on the gastric mucosal damage induced by aspirin, phenylbutazone and reserpine in rats. When given alone, none of them produced any visibly discernible gastric lesions. Their concurrent administration, however, produced some injury to the gastric mucosa which was far less severe than the lesions induced by any of the ulcerogenic drugs used in this study. Pretreatment with nicotine, alcohol and caffeine and their combination resulted in a significant augmentation of gastric lesions produced by aspirin, phenylbutazone and reserpine. These results establish an association between nicotine, alcohol and caffeine in the pathogenesis of gastric ulcers and also implicate them as modifying factors in the genesis of gastric lesions induced by aspirin, phenylbutazone and reserpine.