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At least 379 records · Page 21Linked to original sources
PubMed1976

Ergot alkaloids as dopamine agonists: comparison in two rodent models.

A series of ergot alkaloids, together with the DA agonists apomorphine and piribedil, were tested for protective effects against audiogenic seizures in an inbred strain of mice (DBA/2) and for induction of circling behaviour in mice with unilateral destruction of one nigrostriatal DA pathway. The order of potency against audiogenic seizures was apomorphine greater than ergocornine greater than bromocryptine greater than ergometrine greater than LSD greater than methysergide greater than piribedil while that observed in the rotating mouse model was apomorphine greater than ergometrine greater than ergocornine greater than bromocryptine greater than piribedil. LSD caused only weak circling behaviour even when administered in high doses (greater than 1 mg/kg). Methysergide was ineffective. Prior administration of the neuroleptic agent haloperidol blocked the effect of DA agonists and of ergot alkaloids in both animal models. The possible action of ergot alkaloids as DA agonists is discussed.

Acoustic Stimulation↗
PubMed1986

Studies on the involvement of dopamine D-1 and D-2 receptors in the anticonvulsant effect of dopamine agonists in various rodent models of epilepsy.

Dopamine agonists with different selectivity for dopamine D-1 and D-2 receptors in the brain were tested for their effects: on thresholds for maximal electroshock seizures in mice and rats and for pentylenetetrazol-induced clonic seizures in mice; on seizures induced by air blast stimulation in gerbils, and on seizures induced by amygdala-kindling in rats. The mixed D-1/D-2 agonist apomorphine exerted anticonvulsant effects in all models except kindling. In gerbils and mice, the anticonvulsant action of apomorphine could be antagonized by the D-2 selective dopamine antagonist sulpiride. When injected alone, sulpiride exerted no significant effect on seizure activity. The preferential D-2 receptor agonists lisuride and (+)-PHNO [+)-4-propyl-9-hydroxynaphthoxazine) differed in their profile of action. Both compounds displayed anticonvulsant efficacy in gerbils, while only lisuride proved capable of reducing kindled seizure severity. (+)-PHNO increased the threshold for electroconvulsions in mice while lisuride was ineffective in this respect or even decreased the threshold. The reverse was obtained in regard to electroshock seizures in rats. The threshold for seizures induced by pentylenetetrazol in mice was increased significantly by lisuride but not by (+)-PHNO. The selective dopamine D-1 receptor agonist SKF 38393-A exerted no anticonvulsant effect in any seizure test except a moderate increase of the electroconvulsive threshold in mice. In contrast, the dopamine precursor L-DOPA (injected after pretreatment with carbidopa) proved capable of reducing seizure activity in all models. In mice, the increase in the threshold for maximal electroshock seizures induced by L-DOPA was significantly reduced by sulpiride, which also attenuated the anticonvulsant effect of L-DOPA in gerbils. Collectively, the data indicate that dopamine D-2 receptors mediate the anticonvulsant effect of dopamine agonist and, at least in part, of L-DOPA whereas D-1 receptors seem not to be involved.

Animals↗
PubMed1992

Activation of metabotropic receptors has a neuroprotective effect in a rodent model of focal ischaemia.

The role of the glutamate 'metabotropic' receptor was investigated in an experimental model of focal ischaemia-induced neurodegeneration. The metabotropic agonist, trans-1-amino cyclopentane-1,3-dicarboxylic acid (t-ACPD, 20 mg/kg i.p.), was administered to mice immediately after middle cerebral artery occlusion (MCAO), which causes cerebral infarct. Seven days after MCAO, the mean infarct volume value of the t-ACPD-treated group (mean +/- S.E. = 4.57 +/- 0.73 mm3) was significantly reduced, by 34.3%, compared to the vehicle-treated group (mean +/- S.E. = 6.95 +/- 0.59 mm3, P less than 0.01). This suggests that metabotropic receptor activation in the adult brain reduces excitotoxicity.

Animals↗
PubMed1992

A rodent model of focally evoked self-sustaining status epilepticus.

We describe a novel model of status epilepticus produced by the focal application of bicuculline methiodide into the deep prepiriform cortex of rats pretreated with lithium chloride. Three out of eight rats pretreated with one dose of lithium (3 mmol/kg) 24 h prior to induction of seizures by focal bicuculline, and eight out of 12 rats pretreated with two doses of lithium (at 24 and 48 h) prior to seizure induction, exhibited continual uninterrupted convulsive seizure activity (status epilepticus) lasting between 10 min and > 2 h. This status epilepticus which was manifest both behaviorally and electroencephalographically, was sensitive to reversal by diazepam (5 mg/kg i.p.) given as long as 2 h after the onset of sustained status epilepticus. Pilocarpine (25 mg/kg) pretreatment also predisposed to status epilepticus in response to the focal application of bicuculline, but diazepam (5 or 10 mg/kg i.p.) was ineffective in suppressing the status epilepticus in the presence of pilocarpine.

Animals↗
PubMed1993

Contrasting effects of adenosine A1 and A2 receptor ligands in different chemoconvulsive rodent models.

The pro- and anticonvulsive properties of selective adenosine A1 and A2 receptor agonists and antagonists were investigated in mice using seizure models involving a specific blockade of adenosine A1 and A2 receptors, modulation of the gamma-aminobutyric acid/benzodiazepine receptor complex or activation with the excitatory amino acid glutamate. The selective adenosine A1 receptor agonists N-cyclopentyladenosine (CPA) and R-N-(phenylisopropyl) adenosine (R-PIA) in doses of 1 and 10 mg/kg i.p. potentiated seizures induced by the selective adenosine A1 receptor antagonist 8-[4-[[[[(2-aminoethyl)amino]carbonyl]methyl]oxy]-phenyl]- 1,3-dipropylxanthine (XAC). Likewise, the selective adenosine A2 receptor agonists N-[(2-methylphenyl)methyl]adenosine (metrifudil) and N-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine (DPMA), in doses of 30 and 100 mg/kg i.p., respectively, potentiated seizures induced by the selective adenosine A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine (DMPX). In contrast, the adenosine A1 and A2 receptor agonists both antagonized seizures induced by methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM--an inverse agonist at benzodiazepine receptors) and the adenosine A1 receptor agonists also protected against seizures induced by glutamate. Paradoxically, the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT) antagonized DMCM- and pentylenetetrazole-induced seizures. Thus, it appears that adenosine A1 and A2 receptor agonists can be both pro- and anticonvulsive depending on the mechanism of action of the chemoconvulsant used in the seizure model. The findings with CPT suggest that other types of adenosine analogues than agonists may possess anticonvulsive properties.

Animals↗
PubMed1989

Asymmetrical perfusion fixation in a rodent model of perinatal hypoxia-ischemia may lead to artifactual morphologic asymmetries.

We have observed asymmetries in perfusion between the cerebral hemispheres in immature rats previously subjected to carotid ligation in a model of perinatal hypoxia-ischemia. These asymmetries are associated with marked differences in the number of neurons stained positive by immunoperoxidase protocols for cholinergic neurons utilizing a monoclonal antibody to choline acetyltransferase. These differences are likely to be spurious and due to the asymmetry of perfusion, because fewer stained neurons appear on the unligated side of control animals, in the absence of gliosis or neuron loss. We recommend that quantitative morphologic studies in this model be performed on immersion-fixed specimens.

Animals↗
PubMed1991

Plasmodium berghei: lactic acidosis and hypoglycaemia in a rodent model of severe malaria; effects of glucose, quinine, and dichloroacetate.

Fulminant malaria infections are characterised by hypoglycaemia and potentially lethal lactic acidosis. In young adult Wistar rats (n = 26) infected with Plasmodium berghei (ANKA strain), hyperparasitaemia (greater than 50%), anaemia (PCV 19.6 +/- 5.3%; mean +/- SD) hypoglycaemia (1.04 +/- 0.74 mmol/litre), hyperlactataemia (13.2 +/- 2.20 mmol/litre), hyperpyruvicaemia (0.51 +/- 0.12 mmol/litre) and metabolic acidosis (arterial pH 6.96 +/- 0.11) developed after approximately 14 days of infection. Hypoglycaemia was associated with appropriate suppression of plasma insulin concentrations. In a second series of experiments the metabolic effects of treatment with glucose (500 mg/kg/hr), quinine (5 mg/kg bolus followed by 10 mg/kg over 1 hr) and a potent activator of pyruvate dehydrogenase, dichloroacetate (300 mg/kg) were studied over a 1-hr period. In control animals quinine had no measurable effects, but dichloroacetate significantly reduced arterial blood lactate (74%) and pyruvate (80%). In infected animals, glucose infusion attenuated the rise in lactate (38% compared with 82%; P less than 0.01) but quinine had no additional metabolic effects. Dichloroacetate further attenuated the rise in lactate (14%; P less than 0.01).

Acid-Base Equilibrium↗
PubMed1994

Rodent models of memory dysfunction in Alzheimer's disease and normal aging: moving beyond the cholinergic hypothesis.

The Stone maze paradigm has been developed for use as a rat model of memory impairment observed in normal aging and in Alzheimer's disease. Results from several studies have demonstrated the involvement of both cholinergic and glutamatergic systems in acquisition performance in this complex maze task. Although results of clinical studies on the cognitive enhancing abilities of cholinomimetics for treatment of memory impairment in Alzheimer's disease have been inconsistent, new classes of cholinesterase inhibitors offer greater potential for therapeutic efficacy. The physostigimine derivative, phenserine, appears to have marked efficacy for improving learning performance of aged rats or of young rats treated with scopolamine in the Stone maze. Declines in markers of glutamatergic neurotransmission in Alzheimer's disease and in normal aging suggest that pharmacological manipulation of this system might also prove beneficial for cognitive enhancement. Treatment with glycine and/or polyamine agonists is suggested as a strategy for activating the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. In addition, the use of combined pharmacological activation of cholinergic and glutamatergic systems is suggested. Manipulation of signal transduction events should also be considered as a strategy for cognitive enhancement. The influx of Ca2+ through the channel formed by the NMDA receptor stimulates the production of the oxyradical, nitric oxide (NO*), via the action of nitric oxide synthase (NOS). Compounds that inhibit NOS activity impair acquisition in the Stone maze, suggesting an involvement of NO*. Thus, strategies for inducing NO* production to enhance cognitive performance may be beneficial. Because of the potential neurotoxicity for NO*, this strategy is not straightforward. Although many new directions beyond the cholinergic hypothesis can be suggested, each has its potential benefits which must be weighed against its risks. Nonetheless, an important unifying area for neurobiological research examining mechanisms of normal brain aging and of age-related neuropathology, as observed in Alzheimer's disease, might emerge from the identification of NO* as a simple molecule serving vital physiological functions but representing potential for neurotoxicity.

Aging↗
PubMed1995

Effects of neurotensin in a rodent model of tardive dyskinesia.

The role of neurotensin (NT) in a putative model of tardive dyskinesia (TD) was examined in the rat. When administered directly into the ventrolateral striatum of neuroleptic-naive animals, NT (2.5 micrograms/side) elicited vacuous chewing movements. This response was not seen following administration of NT into other striatal regions or the substantia nigra and was suppressed by the NT antagonist SR 48692 (100 micrograms/kg i.p.). Vacuous chewing movements were also seen following chronic administration of fluphenazine decanoate. These movements were likewise suppressed by SR 48692 (10-100 micrograms/kg i.p.), which failed to affect other behavioural responses and was without effect in neuroleptic-naive animals. Our data suggest that increased levels of endogenous NT within the ventrolateral striatum may play a critical role in the development of TD following chronic neuroleptic administration and that NT antagonists may be beneficial for the treatment of this disorder.

Animals↗
PubMed1996

Neuroprotective effects of alpha-lipoic acid and its enantiomers demonstrated in rodent models of focal cerebral ischemia.

The purpose of this study was to investigate whether alpha-lipoic acid (LA), the oxidized form of the radical scavenger dihydrolipoic acid (DLA), protected brain tissue against ischemic damage and whether there were differences in the neuroprotective potencies between its enantiomers. We used the models of focal cerebral ischemia in mice and rats. The infarct area on the mouse brain surface and the infarct volume of the rat brain were determined by means of an image analyzing system. The LA was capable of reducing the infarct area only when it was administered subcutaneously, but not when it was administered intraperitoneally or into the cisterna magna. Both the R- and the S-enantiomer of LA protected brain tissue against ischemic damage, but their protective activities seemed to be related to the time period of pretreatment. In mice, both enantiomers revealed a similar neuroprotective potency when they were administered subcutaneously 1 or 2 hr before occlusion of the middle cerebral artery (MCA), whereas a longer time period of pretreatment (4 or 6 hr) failed to exert neuroprotection. In rats, subcutaneous pretreatment with R- or S-LA for 2 hr before ischemia significantly diminished the infarct volume. We assume that LA has to be reduced to DLA which finally causes neuroprotection.

Animals↗
PubMedDate not supplied

Antimalarial activity of rifampicin in vitro and in rodent models.

The antimalarial activity of rifampicin, a specific inhibitor of bacterial ribonucleic acid (RNA) polymerase, was confirmed with Plasmodium falciparum in vitro and with P. chabaudi in vivo. The viability of ring forms of P. falciparum, measured by [3H]hypoxanthine and [14C]isoleucine uptake, was significantly reduced within 5 h of exposure to 2.5 microM rifampicin, the 50% inhibitory concentration. Streptolydigin and tagetitoxin, other specific inhibitors of bacterial RNA polymerase, were much less effective as antimalarials. A rifampicin-tolerant sub-line of P. falciparum was selected in vitro. When released from drug pressure, the tolerant line showed appreciably greater rates of incorporation of precursors and growth than the parent line, but over a period of months these characteristics gradually reverted. Rifampicin was effective against a chloroquine-resistant line of P. falciparum and the rifampicin-tolerant line had increased chloroquine sensitivity. Treatment of patent parasitaemias of P. chabaudi in mice with more than 100 mg/kg rifampicin twice daily significantly reduced the parasitaemia within 24 h and parasites were barely detectable on blood films by the fourth day. Recrudescence occurred on release of drug pressure.

Aminoglycosides↗
PubMed1992

Rodent model of nicotine abstinence syndrome.

Few animals models are currently in use for the recognized clinical problem of nicotine dependence and abstinence. This study introduces a rapid and convenient model using the rat. Sixteen male rats were rendered nicotine dependent by 7 days of continuous subcutaneous infusion of either 3 mg/kg/day (n = 8) or 9 mg/kg/day (n = 8) nicotine tartrate salt; 8 control rats were infused with saline alone. Rats were observed for 15 min before, during, and after the drug infusion period using a tally sheet modified from a standard checklist of opiate abstinence signs. There were few signs observed in any group at baseline and at the end of the infusion period. However, nicotine-infused rats showed a significant, dose-related increase over the control group at 16 h after the end of infusion, largely subsiding by 40 h. The most frequently observed signs during withdrawals included: teeth-chattering/chews, writhes/gasps, ptosis, tremors/shakes, and yawns. A significant drop in locomotor activity and increase in weight gain following termination of nicotine infusion provided additional evidence of an abstinence syndrome. This syndrome was alleviated by SC administration of 0.4 mg/kg nicotine tartrate.

Animals↗
PubMed1991

Sex and strain differences in the circadian rhythm fluctuation of endocrine and immune function in the rat: implications for rodent models of autoimmune disease.

This study compares 24-h basal patterns of corticosterone and immunoreactivity for Lewis and Fischer (F344) strain rats. Significant differences in the circadian rhythm of plasma corticosterone were found across sex and strain. Male Lewis rats exhibited significantly lower 24-h corticosterone levels relative to female Lewis and male F344 rats. In addition, male Lewis rats were found to have higher mononuclear cell counts than female Lewis or male F344 rats, particularly in the peripheral blood and spleen compartments. Levels of CD4-bearing lymphocytes in blood, lymph node, and spleen were found to be higher in Lewis rats compared to the F344 strain over a 24-h period. In general, percentages of CD8- and major histocompatibility complex (MHC) class II-bearing lymphocytes were shown to vary over 24 h in all compartments across strains. Given that the Lewis rat has low basal levels of circulating corticosterone, and comparatively higher numbers of CD4-bearing lymphocytes, these factors may play a causative role in the known susceptibility of this strain to many experimental models of autoimmune disease.

Animals↗
PubMed1984

Pathogenesis of hypoxic-ischemic brain injury in a perinatal rodent model.

Exposure of immature rats to 8% oxygen after unilateral carotid artery ligation (UCL) causes metabolic, neurochemical and histopathological changes in the ipsilateral forebrain that resemble those in human perinatal hypoxic-ischemic encephalopathy. Regional cerebral perfusion in this model was examined by visual analysis of India ink trapped in cerebral vessels and measurement of [14C]iodoantipyrine [( 14C]IAP) and [3H]flunitrazepam extraction into the brain. UCL alone reduced [14C]IAP accumulation in the ipsilateral hemisphere by 20% and hypoxia superimposed on UCL progressively reduced ipsilateral hemisphere perfusion by 71% at 2 h. Hypoxia probably injures neurons in this model by causing a critical reduction in cerebral perfusion, an effect which also appears to be important in the human disorder.

Animals↗
PubMed1985

Evaluation of the 5-hydroxytryptamine receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin in different rodent models of epilepsy.

The effects of the serotonin (i.e. 5-hydroxytryptamine; 5-HT) S1 receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and the 5-HT precursor L-5-hydroxytryptophan (5-HTP) were compared in different models of epilepsy. 5-HTP significantly increased the threshold for electroconvulsions and pentylenetetrazol-induced seizures in mice and rats but exerted no anticonvulsant effects in epileptic gerbils and amygdaloid-kindled rats. The anticonvulsant effect of 5-HTP against electroconvulsions in rats could be attenuated by the S2 receptor antagonist, ketanserin. 8-OH-DPAT displayed no anticonvulsant effects in the seizure models examined but gave rise to proconvulsant effects in mice. Differences between 5-HTP and 8-OH-DPAT were also observed in terms of behavioural changes in response to both drugs. The data indicate that S2 receptors may be involved in the anticonvulsant effect of 5-HTP.

8-Hydroxy-2-(di-n-propylamino)tetralin↗