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Some behavioural effects of carbamazepine - comparison with haloperidol

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The experiments presented in this paper aimed to investigate the influence of atypical antiepileptic drug carbamazepine (CBZ, CAS 298-46-4) classified also as normothymic drug on spatial memory in Morris water maze test and anxiolytic effect in two-compartment exploratory test in rats. The study also investigated the probably occurring side effects (measuring cataleptic activity and motor coordination) following single and chronic administration of CBZ compared to haloperidol (HAL, CAS 52-86-8), a conventional antipsychotic. All the tests were carried out on male Wistar rats. CBZ 30 mg/kg was administered orally 60 min before the tests and HAL 0.15 mg/kg was administered orally 60 min before the tests. In the Morris test memory improvement only after chronic administration of CBZ on the 7 and 14 day of treatment was observed, whereas after 14 days of HAL treatment spatial memory impairment was noted. In the two-compartment exploratory test 30 mg/kg of CBZ had an anxiolytic effect after 7 and 14 days of treatment, whereas HAL did not show anxiolytic effect after single and chronic treatment. CBZ did not induce catalepsy after single as well as chronic administration. HAL evoked a strong cataleptic effect both after acute and chronic treatment. CBZ had no impact on motor coordination in the chimney test and HAL disturbed motor coordination in rats after single as well as chronic administration. CBZ may be an useful normothymic drug using in bipolar affective disorder treatment with co-occurred anxiety and cognitive deficits. The lack of significant side effects of CBZ may be an alternative way of treatment in comparison with older drugs, such as lithium carbonate.
The aim of present study was to evaluate mechanisms involved in thermomodulatory effect LPK in rats.Experiments were performed on adult Wistar male rats. LPK was applied either intracerebroventricularly (icv), or intraperitoneally (ip) using the similar program and technique of experiments as in our previous study. We confirmed in this paper the results of our previous reports that icv administration LPK at the dose of 20 nmol induced evident significant rectal hypothermia, while lower dose LPK of 1 nmol icv exerted significant hyperthermic effect. Peripherally applied LPK at the range of doses 10-100 nmol/100 g ip displayed slight bimodal (hyperthermic and hypothermic) effect on rectal temperature. Prior administration of haloperidol, an antagonist of central dopamine receptors blocked both effects LPK applied either icv or ip. Obtained results indicate that both hypothermic and hyperthermic effects LPK are also modulated by central dopaminergic receptors.
On the morning of the first day of pregnancy, Wistar rats were administered a single IP injection of either zinc sulfate (10.0 mg/kg) or saline. For the remainder of pregnancy, half the rats in each group then consumed filtered tap water while the other half consumed filtered tap water with 50 ppm of cadmium (CdCl₂ ). At eight weeks after birth, the behavioral profile of male offspring was assessed in the following way: Apomorphine (non-selective dopamine receptor agonist), (+)-7-hydroxy-2-(di-n-propylamino) tetralin (7-OH-DPAT) (D₃ agonist) and (+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SKF 38393) (D₁ agonist) were used to evaluate stereotyped behavior, yawning activity and oral movements – indices for these respective agonists. In addition, two dopamine receptor antagonists, haloperidol (D₂ antagonist) and 7-chloro-8-hydroxy3-methyl-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzapine (SCH 23390) (D₁ antagonist) were used to evaluate cataleptogenic activity. Additional behavioral parameters studied were locomotor activity, irritability and reaction to a painful stimulus. Dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT) were quantified in the striatum, hippocampus and in the frontal cortex of the brain by means of HPLC/ED technique. In addition, cadmium levels were analyzed in the brain, liver, kidney and bone of newborn rats. Our results indicate that prenatal exposure of pregnant rats to cadmium produced alterations in the reactivity of central dopamine receptors and modulated the level of dopamine and its metabolites in the offsprings’ brains. A single injection of zinc, preceding cadmium consumption, attenuated some of the effects of cadmium on the offsprings’ dopaminergic system. Zinc also reduced cadmium deposition in the brain, kidney and bone, but enhanced its accumulation in liver. In summary, zinc may exert some neuroprotective effects against cadmium neurotoxicity.
The effects of a repeated treatment with antipsychotic drugs, clozapine and haloperidol, on the modulation of network activity ex vivo by 5-HT receptors were examined in rat frontal cortical slices using extracellular recording. Rats were treated for 21 days with clozapine (30 mg/kg p.o.), or haloperidol (1 mg/kg p.o.). Spontaneous bursting activity was induced in slices prepared 3 days after the last drug administration by perfusion with a medium devoid of Mg2+ ions and with added picrotoxin (30 mM). The application of 2-3 µM 8-OH-DPAT, acting through 5-HT1A receptors, resulted in a reversible decrease of bursting frequency. In the presence of 1 µM DOI, the 5-HT2 agonist, or 5 µM zacopride, the 5-HT4 agonist, bursting frequency increased. Chronic clozapine treatment resulted in an attenuation of the effect of the activation of 5-HT2 receptors, while the effects related to 5-HT1A and 5-HT4 receptor activation were unchanged. Treatment with haloperidol did not influence the reactivity to the activation of any of the three 5-HT receptor subtypes. These data are consistent with earlier findings demonstrating a selective downregulation of 5-HT2A receptors by clozapine and indicate that chronic clozapine selectively attenuates the 5-HT-mediated excitation in neuronal circuitry of the frontal cortex while leaving the 5-HT-mediated inhibition intact.
Ethanol (EtOH) abuse in pregnancy is know to seriously damage the internal organs of the fetus, a condition in humans that is classified as "fetal alcohol syndrome". Aluminium (Al) can develop neurotoxic effects and contribute to some neurological disorders. To test whether the reactivity of some central receptors (dopamine - DA, serotonin-5-HT and muscanne - M) may be altered by prenatal EtOH and Al, administered separately or jointly, female rats were given 10% (v/v) EtOH and/or Al(600 or 3000 ppm) throughout pregnancy in their drinking water. Male adult offspring were tested at 3 months for behavioural effects know to be induced by agonists acting at different subtypes of DA (D1 D2, D3,), 5-HT2t and M receptors. Addition antagonist of D, receptor have been examined. The substances SKF 38393, quinpirole, mCPP, pilocarpine, haloperidol, and the behavioral procedures of yawning, oral activity and catalepsy have been used for assessment. The results of the experiment indicate that EtOH does not modify the effect of the central DA and M receptor agonist and DA antagonist in Al prenataly exposed rats. On the other hand, EtOH modified the reactivity of the central 5-HT2c receptor to agonist (mCPP) in Al pretreated rats.
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