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At least 973 records · Page 54Linked to original sources

The ameliorating effects of the cognitive-enhancing Chinese herbs on scopolamine-induced amnesia in rats.

Ameliorating effects were investigated of the cognitive-enhancing Chinese herbs administered orally for 1 week-Panax ginseng (PG), Panax notoginseng (PNG), Dioscorea opposita (DO), Gastrodia elata (GE), Salvia miltiorrhiza (SM), Acorus gramineus (AG), Coptis chinensis (CC), Polygonum multiflorum (PM), Cyperus rotundus (CR) and Psoralea corylifolia (PC)-on the scopolamine (SCOP)-induced amnesia by using a passive avoidance task in rats. Of ten Chinese herbs, only PG, PNG, GE and CC prolonged the SCOP-shortened STL. These results revealed that PG, PNG GE and CC administered orally for 1 week improved the SCOP-induced learning and memory deficit in rats.

Administration, Oral↗

Liquid chromatographic determination of hyoscine (scopolamine) in urine using solid phase extraction.

A sensitive method for the determination of hyoscine (scopolamine) in urine is described. After concentration and "clean-up" on C18 and CN solid phase extraction columns, hyoscine was quantified by high performance liquid chromatography with coulometric detection (oxidation at +0.9 V). The limit of detection was 5 ng per sample and the precision for 5 mL samples containing 2 ng/mL was 12.3%. The method was applied to urine samples collected from 12 volunteers wearing Scopoderm TTS patches. The mean excretion rate of unmetabolized hyoscine was 0.45 micrograms/h and 87% of the total hyoscine was present as conjugates. Apohyoscine (aposcopolamine) was identified as a urinary metabolite. The significance of this with regard to hyoscine assays is discussed.

Chromatography, High Pressure Liquid↗

A rapid densitometric method for the analysis of hyoscyamine and scopolamine in solanaceous plants and their transformed root cultures.

A rapid and convenient method for sample preparation and simultaneous densitometric quantification of hyoscyamine (1) and scopolamine (2) has been developed. The alkaloid profiles of plant samples, as well as the content of 1 and 2, determined by TLC-densitometry corresponded well with those obtained using a GC method. The proposed method is simple and sensitive and can be used for the routine assay of 1 and 2, and for screening for alkaloid-rich and biochemically-interesting transformed root cultures and intact solanaceous plants.

Atropine↗

Differential effect of MK 801 and scopolamine on c-fos expression induced by L-dopa in the striatum of 6-hydroxydopamine lesioned rats.

In rats with a unilateral 6-hydroxydopamine lesion of the dopaminergic nigro-striatal pathway, striatal D1-receptor-stimulated c-fos expression and turning behavior are positively modulated by D2 receptor stimulation and by blockade of N-methyl-D-aspartate (NMDA) or muscarinic receptors. Combined D1/D2 receptor stimulation by L-dopa activates c-fos in a manner not additive with muscarinic receptor blockade by scopolamine. On the other hand, blockade of NMDA receptors by MK 801 reduced c-fos expression induced by L-dopa while, depending on the dose of L-dopa, differentially affecting contralateral turning behavior. The results are interpreted to suggest that D2 receptor stimulation amplifies D1-receptor-mediated c-fos expression by two mechanisms differentially related to muscarinic and NMDA receptors.

Animals↗

Efficacy comparison of scopolamine and diazepam against soman-induced debilitation in guinea pigs.

The efficacy of diazepam (DZ) and scopolamine (SCP), in combination with atropine (ATR)+oxime therapy, against soman-induced seizure/convulsive activity and associated brain damage has been demonstrated, but the efficacy of each against the incapacitating effects of soman has not been addressed. Thus, the therapeutic efficacies of SCP (5 doses; 0-0.86 mg/kg) and DZ (5 doses; 0-5 mg/kg), when each was used in conjunction with ATR (3 doses; 0.5-8 mg/kg) + 2-PAM (25 mg/kg) therapy, were compared in groups of pyridostigmine pretreated guinea pigs exposed to 1.6, 2.0, 2.5, or 3.2 LD50s of soman. Response surface methodology was employed to describe the relationship between soman-induced incapacitation and the ATR/DZ or ATR/SCP dosages. Incapacitation was measured by toxicity scores assigned by three graders to test animals at 60 min postsoman. Results show that as the dosage of SCP increased, the mean toxicity scores decreased. Also, within the indicated dose ranges used, the efficacy of SCP was not dependent on the presence of ATR. In contrast, ATR alone was found to be more effective than when combined with DZ at any dose, and indicates that DZ might be temporarily contributing to soman-induced incapacitation. These findings suggest that in guinea pigs, SCP could replace ATR or DZ, or both, as therapy against soman-induced incapacitation.

Animals↗

Effects of scopolamine on spatial working memory in rats pretreated with the serotonergic depleter p-chloroamphetamine.

The present study investigated the mnemonic consequences of muscarinic blockade in rats pretreated with the serotonergic depleter p-chloroamphetamine (PCA). Subjects were initially injected with either PCA (2.5 mg/kg) or saline (SAL) approximately 1 week prior to testing on a working memory version of the Morris water maze (four daily trials for 4 days). Fifteen minutes before each daily session, PCA- and SAL-pretreated subjects were injected either with SAL or with one of two doses of scopolamine (SCOP; 0.5, 1.0 mg/kg). Latency to find the platform on each trial served as the major dependent measure. The results indicated that SCOP increased escape latencies. However, the dose needed to produce this effect was dependent upon whether subjects were pretreated with PCA. Significant increases in escape latencies in SAL-pretreated rats were induced with 1.0 mg/kg SCOP (on Day 1), while 0.5 mg/kg SCOP produced the same effect in PCA-pretreated subjects (on Days 1-4). Thus, although it was clearly demonstrated that muscarinic blockade did impair spatial working memory, the present data indicated that the dose necessary to produce this effect was dependent upon the status of the serotonergic system. More generally, these results imply that the cholinergic and serotonergic systems interact in a functionally important, as yet undetermined manner.

Animals↗

Intrahippocampal scopolamine impairs both acquisition and consolidation of contextual fear conditioning.

Lesions of the dorsal hippocampus have been shown to disrupt both the acquisition and the consolidation of memories associated with contextual fear (fear of the place of conditioning), but do not affect fear conditioning to discrete cues (e.g., a tone). Blockade of central muscarinic cholinergic receptor activation results in selective acquisition deficits of contextual fear conditioning, but reportedly has little effect on consolidation. Here we show for the first time that direct infusion of the muscarinic cholinergic receptor antagonist, scopolamine, into the dorsal hippocampus produces a dose-dependent deficit in both acquisition and consolidation of contextual fear conditioning, while having no impact on simple tone conditioning.

Animals↗

Usefulness and safety of pirenzepine in double-contrast study of upper gastrointestinal tract: comparison with scopolamine methylbromide.

To evaluate usefulness of pirenzepine, a selective M1 antimuscarinic drug, for diagnostic double-contrast study of the upper gastrointestinal tract, pirenzepine and scopolamine methylbromide (SMB) were compared in a single blind randomized trial. Seventy consecutive patients were enrolled in the study. Artifacts, bowel distention, painting of stomach and duodenal bulb, and global quality of the images were blindly evaluated by four independent observers by means of a numerical score (1-4). Under SMB slightly but significantly better results for stomach were scored (3.1 +/- .7 vs. 2.7 +/- 7, p < 0.01). No differences were found in the study of the duodenal bulb. Heart rate and rhythm during the study were recorded by electrocardiogram (ECG). SMB induced tachycardia in all patients (from 77 +/- 20 to 117 +/- 28 beats/min, p < 0.01) while pirenzepine did not (from 77 +/- 16 to 81 +/- 23, p = NS). After SMB, two patients exhibited faintness, and some patients complained of visual accommodation defects, dryness of the mouth, and dizziness. Thus, pirenzepine provides good results in double-contrast studies (equal to SMB), while presenting no adverse effects. It could be proposed as a first choice hypotonic agent in upper gastrointestinal examination.

Adult↗

Effects of scopolamine and d-amphetamine on locomotor activity before and after shock: a diallel analysis in mice.

The effect of shock on locomotor activity was evaluated in three strains of mice (A, DBA/2 and C57BL/6) after treatment with scopolamine (1.0 mg/kg) and d-amphetamine (10.0 mg/kh). The effectiveness of either drug in incrasing locomotor activity was strain dependent. Both drugs eliminated behavioral suppression induced by shock, and in A and DBA/2 mice shock augmented the locomotor stimulation induced by d-amphetamine. In another experiment the behavior of the 6 F1 hybrids was examined in relation to the parent strains. It was observed that locomotor activity in the F1's could resemble that seen in one parent in the saline condition, but the other parent after treatment with d-amphetamine. Similarly, the F1 behavior in the amphetamine condition was not predictive of the behavior seen after shock plus amphetamine. The results suggest that general activity, locomotor activity after amphetamine treatment, and responsiveness following shock in amphetamine-treated mice are mediated by different genetic mechanisms.

Animals↗

Bilateral skin conductance and the pupillary light-dark reflex: manipulation by chlorpromazine, haloperidol, scopolamine, and placebo.

Cholinergic blocking with scopolamine produces skin conductance orientating response (SCOR) nonresponding in normal subjects. This may be one of a number of causes for nonresponding in schizophrenic subjects. Blockade of dopamine with haloperidol produces an increase in amplitude and shortening of recovery time in the SCOR of normal subjects. This result closely resembles that of Nielsen and Petersen (1976) who found a similar pattern of responding in normal subjects who scored high on a scale of schizophrenism. These results, along with those for chlorpromazine and the pupillographic effects of the three drugs are discussed in terms of biochemical working hypotheses of schizophrenic subclassification.

Adult↗

Long-term stress-induced analgesia blocked by scopolamine.

An 'opioid' form of analgesia ('long-term analgesia') was completely blocked by scopolamine. This effect of a muscarinic antagonist suggests that muscarinic cholinergic processes may play an important role in this analgesia and in other types of endogenous pain control.

Animals↗

The effects of pre-exposure to scopolamine on subsequent drug state discrimination.

This experiment was done to test the prediction that preexposure to a drug state would increase the discriminability of that drug state when used as a cue in a discrimination task. Eight rats were pre-exposed to scopolamine for 20 days and 8 rats were given saline injections. The drug pre-exposed animals acquired a drug state discrimination more quickly than the controls. A difference was also found between the generalization gradients for each group with the pre-exposed group showing a steeper generalization gradient.

Animals↗

Time course of decline of radiolabeled acetylcholine formed following intracerebroventricular administration of tritiated choline: effects of oxotremorine and scopolamine.

Rats were injected intracerebroventricularly with 5 microCi of [methyl-3H]choline. The time course of decline of the radiolabeled acetylcholine (ACh) formed was estimated in the ipsilateral cerebral cortex and striatum. The [3H]ACh levels declined biphasically from the cerebral tissue. The initial decline proceeded rapidly, after which labeled ACh declined more slowly. Scopolamine (1 mg/kg, i.v.) caused a significant increase in the rate of [3H]ACh disappearance, which can be interpreted as an enhancement of ACh release. By contrast, oxotremorine (0.8 mg/kg, i.v.) markedly reduced the [3H]ACh disappearance. The results show that drug-induced changes in cholinergic neuronal activities can be estimated from the disappearance of radioactive ACh after labeling the endogenous transmitter through intracerebroventricular administration of labeled choline.

Acetylcholine↗

Effect of oxotremorine, physostigmine, and scopolamine on brain acetylcholine synthesis: a study using HPLC.

The synthesis rate of brain acetylcholine (ACh) was estimated in mice following i.v. administration of [3H]choline (Ch). The measurements were performed 1 min after the tracer injection, using the [3H]ACh/[3H]Ch specific radioactivity ratio as an index of ACh synthesis rate. Endogenous and labeled Ch and ACh were quantified using HPLC methodology. Oxotremorine and physostigmine (0.5 mg/kg, i.p.) increased the steady state concentration of brain ACh by + 130% and 84%, respectively and of Ch by + 60% (oxotremorine); they decreased ACh synthesis by 62 and 55%, respectively. By contrast, scopolamine (0.7 mg/kg, i.p.) decreased the cerebral content of Ch by - 26% and of ACh by - 23% without enhancing the synthesis of ACh. The results show the utility of HPLC methodology in the investigation of ACh turnover.

Acetylcholine↗

Chronic treatment with choline or scopolamine indicates the presence of muscarinic cholinergic receptor plasticity in the frontal cortex of young but not of aged mice.

Chronic treatment (2 weeks) with either scopolamine (4 mg/kg, once daily p.o.) or choline (200 mg/kg, once daily p.o.) resulted in a pronounced muscarinic cholinergic receptor up- or down-regulation in the frontal cortex of young (4 weeks) but not of aged (18 months) female mice. It is speculated that a similar age-related decline of muscarinic receptor plasticity might contribute to the profound dysfunction of cholinergic neurotransmission in Alzheimer's disease.

Aging↗

Cognitive effects of scopolamine in dementia.

Cholinergic deficiency was postulated to play an important role in the mental decline observed in Alzheimer's (AD), Parkinson's (PD) and multiinfarct (MID) dementia. In the present study, 11 AD, 8 MID and 7 PD patients (DSM III-R diagnostic criteria for dementia) and 9 healthy age-matched controls (CTRL) were given IV 0.5 mg scopolamine (SCO) or placebo (PLA) in random order (double blind) within one week. The Hebrew Short Mental Test (SMT) and Wechsler Memory Scale (WMS) were administered before and after SCO and PLA in each patient. A comparison of SCO vs. PLA utilizing MANCOVA (the covariate being the basal mental performance [BAS] with SMT or WMS) showed that SCO affected all the groups similarly, except for the Wechsler subtest of logic memory which showed larger deterioration in CTRL compared to demented patients. ANOVA and MANCOVA analyses did not distinguish between the three demented groups. SCO administration does not differentiate between demented patients and CTRL and does not enable discrimination between patients with AD, MID and PD. Moreover, some CTRL with still normal cognitive performance, but lower BAS may be more vulnerable to SCO than others. The integrity of the cholinergic system may be responsible for the different sensitivity to SCO challenge.

Aged↗

A comparison of the effects of scopolamine and diazepam on working memory.

Two drug models of memory dysfunction, namely the benzodiazepine and the cholinergic models, have emerged from the considerable number of studies which have examined drug effects on information processing. The reported impairments produced by administration of compounds from these two families appear to be more similar than dissimilar, and to date, direct comparisons on traditional memory tasks have failed to differentiate the models. This study compared the effects of diazepam and scopolamine on tasks associated with separable components of working memory. The results indicate that this model also fails to discriminate between the drug models; both compounds selectively impaired tasks associated with the central executive mechanism and failed to disrupt tasks associated with the articulatory loop or the visuospatial scratchpad.

Adolescent↗

Effects of (R)-alpha-methylhistamine and scopolamine on spatial learning in the rat assessed using a water maze.

The effects of (R)-alpha-methylhistamine ((R)-alpha-MeHA, a selective H3-receptor agonist) and scopolamine (SCOP, a muscarinic antagonist) were investigated on spatial learning and memory in the rat (Hooded Lister) using a water maze (WM). (R)-alpha-MeHA treatment (6.3 and 10 mg/kg IP) had no apparent effect on spatial learning but did result in enhanced spatial recall at the higher dose, assessed by a transfer (probe) test after training. In contrast, SCOP (0.5 mg/kg IP) induced a learning and memory deficit measured both during and after training. In animals treated with (R)-alpha-MeHA and SCOP, (R)-alpha-MeHA partially (6.3 mg/kg) and completely (10 mg/kg) reversed the SCOP-induced deficit during the training phase, while in the post-training transfer test, (R)-alpha-MeHA (10 mg/kg) significantly reduced the SCOP-induced memory deficit. None of the treatments described resulted in impaired visual acuity as demonstrated by a raised platform test. These results are consistent with a role for histamine in cognitive processes and suggest a possible interaction between central histamine and cholinergic mechanisms associated with rodent spatial learning and memory.

Animals↗