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At least 649 records · Page 36Linked to original sources
PubMed2002

Modulatory role of cyclooxygenase inhibitors in aging- and scopolamine or lipopolysaccharide-induced cognitive dysfunction in mice.

Inflammation processes may play a critical role in the pathogenesis of the degenerative changes and cognitive impairments associated with Alzheimer's disease (AD). Non-steroidal anti-inflammatory drugs are reported to be effective in reducing the risk of developing AD or cognitive impairments. Present experiments were performed to study the possible effect of various NSAIDs on cognitive performance of young, aged and scopolamine or lipopolysaccharide (LPS) treated mice (an animal model of AD) using one trial step through type of passive avoidance and in elevated plus maze task. Chronic administration of NSAIDs at the ED(50) doses (nimesulide, rofecoxib and naproxen for 15 days) significantly reversed the age or scopolamine-induced retention deficits in both test paradigms. However, in both the memory paradigms chronic administration of NSAIDs failed to modulate the retention performance of young mice. Acute administration of LPS (50 mcg/mouse, i.p.) significantly exhibited retention deficits after 24 h and seventh day of its administration in both test paradigms. Chronic administration (7 days) of rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor (1.92 mg/kg, p.o.) significantly reversed the LPS-induced retention deficits in both tests. The results of this study showed chronic treatment of NSAIDs reverses the cognitive deficits in age and scopolamine or LPS treated mice. These findings establish a link between the central nervous system expression of various pro-inflammatory cytokines and learning impairment in mice.

Aging↗
PubMed2003

The influence of adenosine A3 receptor agonist: IB-MECA, on scopolamine- and MK-801-induced memory impairment.

The effects of adenosine A3 agonist IB-MECA on scopolamine- and MK-801-induced impairment of spontaneous alternation and learning abilities were examined using Y-maze and passive avoidance tasks in mice. IB-MECA given 20 min before test had no effect on spontaneous alternation performance. Similarly learning abilities tested in passive avoidance were not disturbed after IB-MECA administration before training session. IB-MECA significantly diminished scopolamine- and MK-801-induced impairment of spontaneous alternation in Y-maze and learning abilities in passive avoidance task as well as reduced higher locomotor activity in MK-801-treated group. This ameliorating effect of IB-MECA was not antagonised by adenosine A1 antagonists CPX. Obtained results indicate that adenosine A3 receptor stimulation may ameliorate spatial memory and long term memory impairments in terms of cholinergic and glutamatergic deficits induced by scopolamine and MK-801, respectively.

Adenosine↗
PubMed2004

Scopolamine effects on ultrasonic vocalization emission and behavior in the neonatal mouse.

Developmental alterations of the cholinergic system can lead to short- and long-term detrimental consequences for brain function. In order to study the cholinergic modulation of behavior in the neonatal mouse, we characterized ultrasonic vocalizations and spontaneous behavior of 5- and 8-day old CD-1 Swiss mice after i.p. administration of the muscarinic antagonist scopolamine (doses, 0.8 and 2 mg/kg) during both a first isolation of 30 min and a re-isolation of 5 min, occurring immediately after a brief reunion with the mother. As concerns the first isolation, on PND 5, only scopolamine 0.8m g/kg increased the number of ultrasonic vocalizations and, on PND 8, both doses increased it in a dose-dependent fashion. Scopolamine effects on spontaneous behavior were very limited on PND 5, but markedly evident on PND 8, the high dose increasing activity profile. Independently from treatment, the brief reunion with the mother had no effects on mouse ultrasound emission during re-isolation. The present results show that the cholinergic system plays a role in inhibiting rodent pup USV emission and spontaneous behavior and suggest that the analysis of spontaneous behavior and, in particular, of the number of ultrasonic vocalizations represents a valuable tool to detect precocious developmental alterations of the cholinergic function in the mouse, the most used animal species to model human health disorders.

Age Factors↗
PubMed1998

Intra-amygdala infusions of scopolamine impair performance on a conditioned place preference task but not a spatial radial maze task.

Lesions of the amygdala impair performance on a conditioned place preference (CPP) but not a spatial radial maze task. The role of cholinergic receptors within the amygdala in performance of these tasks was evaluated using intra-amygdala injections of the muscarinic receptor antagonist, scopolamine. Food deprived rats were trained on a CPP task, which consisted of four training trials on two arms of a radial eight-arm maze. One arm was consistently paired with a large amount of food (14 g) while the other arm was never baited. Prior to the fourth trial, rats received bilateral intra-amygdala infusions of the muscarinic receptor antagonist, scopolamine (SCOP; 5 microg/0.5 microl) or vehicle. On a retention test 24 h later, unoperated and vehicle-infused rats, but not SCOP-treated rats, spent significantly more time in the paired arm than chance (50%). Therefore, the scopolamine treatment appeared to block learning and/or memory on trial 4. The same rats were then trained on a radial maze task on the same apparatus, in which rats had access to all eight arms but only four were baited with food (1 pellet). Rats were trained until they reached criterion and then infusions were given prior to testing. SCOP treatment did not affect performance on the radial maze task. Thus, intact cholinergic mechanisms in the amygdala are necessary for learning or memory on a CPP task with a high reward component but not performance on a spatial radial maze task with a lower reward component.

Amygdala↗
PubMed1997

NMDA antagonists potentiate scopolamine-induced amnesic effect.

The effects of N-methyl-D-aspartate NMDA receptor antagonists on scopolamine-induced amnesia and on delay-interposed short-term memory performance were investigated using an 8-arm radial maze in rats. Scopolamine, a muscarinic antagonist, deteriorated the radial maze performance, while MK-801, an NMDA receptor channel blocker and CGS-19755, a competitive NMDA receptor antagonist, showed no obstruction to the spatial cognition in the non-delayed maze task. MK-801 (0.01-0.03 mg/kg, i.v.) and CGS-19755 (1-10 mg/kg, i.v.) significantly augmented scopolamine-induced deficit in the non-delayed maze task and impaired the short-term memory in the 5-min delay-interposed task. These results suggest that NMDA antagonists have a negative action on short-term memory and that the interaction between the NMDA and the central muscarinic system plays a role in modulating the cognitive function.

Amnesia↗
PubMed1999

Spatial signal detection in rats is differentially disrupted by delta-9-tetrahydrocannabinol, scopolamine, and MK-801.

Cannabinoid receptors have been implicated as having important roles in human cognitive processes, especially memory and attention. While some work has studied the effects of the active ingredient in marijuana, delta-9-tetrahydrocannabinol (THC), on short-term memory, no work has examined the involvement of these receptors in mediating attention. Therefore, the present study compared the effects of THC on the performance by rats of an operant spatial signal detection task with those of cholinergic muscarinic antagonist scopolamine and glutamatergic NMDA antagonist MK-801, both compounds known to influence attention and other cognitive processes in rats. These experiments were conducted in a two lever operant chamber in which a cue lamp was mounted over each lever. The rats were pretrained to respond rapidly on the corresponding lever following a rapid presentation of the cue lamp above it. The stimulus was presented in a random order of three durations (100, 300 or 1000 ms) to measure detectability of the stimulus under saline, THC (1.0 or 2.0 mg/kg i.p.), scopolamine (0.06-0.25 mg/kg i.p.), or MK-801 (0.06-0.25 mg/kg i.p.). THC significantly and selectively disrupted stimulus detection accuracy at the 100 ms stimulus duration, but did not influence response bias or the rate of responding. Scopolamine and MK-801 both produced alteration in errors of omission and position bias. These data suggest that THC produces an impairment in visual attention and that the nature of this impairment is qualitatively different from that produced by muscarinic-receptor or NMDA-receptor antagonism.

Animals↗
PubMed1999

Effects of histamine H3 receptor agonists and antagonists on cognitive performance and scopolamine-induced amnesia.

In previous research we found that pre-training administration of histamine H3 receptor agonists such as (R)-alpha-methylhistamine and imetit impaired rat performance in object recognition and a passive avoidance response at the same doses at which they inhibited the release of cortical acetylcholine in vivo. Conversely, in the present study we report that the post-training administration of (R)-alpha-methylhistamine and imetit failed to affect rat performance in object recognition and a passive avoidance response, suggesting that H3 receptor influences the acquisition and not the recall processes. We also investigated the effects of two H3 receptor antagonists, thioperamide and clobenpropit, in the same behavioral tasks. Pre-training administration of thioperamide and clobenpropit failed to exhibit any procognitive effects in normal animals but prevented scopolamine-induced amnesia. However, also post-training administration of thioperamide prevented scopolamine-induced amnesia. Hence, the ameliorating effects of scopolamine-induced amnesia by H3 receptor antagonism are not only mediated by relieving the inhibitory action of cortical H3 receptors, but other mechanisms are also involved. Nevertheless, H3 receptor antagonists may have implications for the treatment of degenerative disorders associated with impaired cholinergic function.

Amnesia↗
PubMed1998

Scopolamine impairs memory recall in Octopus vulgaris.

The involvement of the central cholinergic system in predatory performance, and on the recall of individual and observational memory in Octopus vulgaris was studied by treating the animals with the muscarinic antagonist scopolamine (2 mg/kg). The absence of the effects of the injection of scopolamine on blood circulation was also checked. Scopolamine did not affect the ability of octopuses to prey on live crabs. However, it interfered significantly with memory recall. In fact, the ability to solve the jar problem was impaired within the first hour after injection (short-term effects) and was only partially recovered after 24 h (long-term). Moreover, both individual and observational learning of a visual discrimination were significantly reduced at the short- and long-term testing. These results support a role of the cholinergic system in the processes of memory recall of O. vulgaris.

Animals↗
PubMed2001

Determination of scopolamine in human serum and microdialysis samples by liquid chromatography-tandem mass spectrometry.

A liquid chromatographic-tandem mass spectrometric (LC-MS-MS) method with a rapid and simple sample preparation was developed for the determination of scopolamine in biological fluids. Scopolamine and the internal standard atropine in serum samples were extracted and cleaned up by using an automated solid phase extraction method. Microdialysis samples were directly injected into the LC-MS system. The mass spectrometer was operated in the multi reaction monitoring mode. A good linear response over the range of 20 pg/ml to 5 ng/ml was demonstrated. The accuracy for added scopolamine ranged from 95.0 to 104.0%. The lower limit of quantification was 20 pg/ml. This method is suitable for pharmacokinetic studies.

Calibration↗
PubMed2001

LC determination of atropine sulfate and scopolamine hydrobromide in pharmaceuticals.

An accurate, simple, reproducible and sensitive method for the determination of atropine sulfate and scopolamine hydrobromide has been developed and validated. Atropine sulfate and scopolamine hydrobromide were separated using a microBondapack C(18) column by isocratic elution with flow rate 1.0 ml/min. The mobile phase composition was methanol, water, formic acid (165:35:1; v/v/v) and pH adjusted 8.3 with triethylamine. The samples were detected at 230 nm using photo-diode array detector. The linear range of detection for atropine sulfate (I) and scopolamine hydrobromide (II) were between 10.38 and 1038 microg/ml with a limit of quantification (LOQ) of 10.38, 10.00 and 1034 microg/ml with an LOQ of 10.00 microg/ml respectively. The linearity, range, peak purity, selectivity, system performance parameters, precision, accuracy, robustness and ruggedness for (I) and (II) were also shown acceptable values.

Atropine↗
PubMed2003

Investigation of the effect of space environment on the contents of atropine and scopolamine in Datura metel by capillary zone electrophoresis.

The seeds of Datura metel were carried aboard a retrievable satellite and exposed to space environment. The effects of space environment (weightlessness and ionizing radiation) on the contents of atropine and scopolamine in D. metel were investigated by using an effective capillary zone electrophoresis (CZE) method, which employed 50 mmol/l phosphate buffer (pH 8) containing 10% (v/v) tetrahydrofuran as the running buffer. The results showed that the contents of atropine and scopolamine varied to some extent, and the earth-control group has the lowest content of atropine. However, the variation of atropine and scopolamine contents in three groups was not obvious based on t-test. At the same time, the optimization of the separation was discussed in detail and the two compounds were completely separated within 10 min with satisfactory repeatability and calibration linearity.

Atropine↗
PubMed1999

Intra-striatal haloperidol and scopolamine injections: effects on choice reaction time performance in rats.

In this study the behavioral consequences of intra-striatal haloperidol and scopolamine injections were examined using a reaction time task. Haloperidol was found to increase the response time of the rats and had a modest effect on the motor components of the task. The manner in which haloperidol affected the response time distribution suggested that this drug affected attentional functions. Scopolamine did not affect the reaction time or motor performance in the reaction time task. However, a clear decrease in the number of completed trials and an increase in anticipatory responses was observed. At present no ready explanation could be given for the behavioral effects of scopolamine. The present data suggest that although dopamine and acetylcholine are intimately related in the striatal network and have been supposed to have antagonistic functions, the behavioral consequences of blockade of dopamine and acetylcholine receptors are dissimilar.

Animals↗
PubMed2003

Peripheral 8-OH-DPAT and scopolamine infused into the frontal cortex produce passive avoidance retention impairments in rats.

The present study determined whether peripheral injections of the 5HT(1A) agonist (8-OH-DPAT), scopolamine infusions into the frontal cortex, or a combination of both drug treatments would produce impairments in rats trained on passive avoidance. Using a 2x2 design, rats were infused with either bacteriostatic water or 30 microg/1 microl of scopolamine HCl into the frontal cortex 30 min before being trained on passive avoidance. This was followed by injections (ip) of either 0.1% ascorbic acid/bacteriostatic water or 30 microg/kg of 8-OH-DPAT 15 min later. All subjects were tested for retention 72h later. At test, the initial latency to enter into the black shocked compartment and the total time spent in the white safe compartment (TTW) were recorded. Analysis of the latency data indicated that scopolamine and 8-OH-DPAT, when administered singly or in combination, produced amnesia for the task. Assessment of TTW scores, however, revealed that of the three drug-treated groups, only animals treated with 8-OH-DPAT alone tended to avoid the previously shocked black compartment and spend more time in the white safe compartment. These data indicate that either stimulating 5-HT(1A) or blocking frontal cortical muscarinic receptors at training impairs passive avoidance performance and that the deficit following the latter treatment is somewhat more extensive. Implications for the role frontal cortical muscarinic and 5HT(1A) receptors play in learning and memory are discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2006

Visual side-effects from transdermal scopolamine (hyoscine).

Transdermal scopolamine may be used to reduce drooling in children with disabilities. Side-effects include dilated pupils and a reduction in the near point of accommodation (the closest point at which clear vision is possible). Two male children with epilepsy, one with spinal dysraphism (aged 7y 6mo) and one with cerebral palsy (aged 5y 8mo), who have undergone treatment for drooling with transdermal scopolamine are described. Near visual acuity was reduced, and both children showed dilated pupils with reduced or no response to light. These responses became normal on cessation of the scopolamine patch. As the effect of this drug may be cumulative, and many patients are unable to communicate difficulties, clinicians need to be aware of these possible side-effects.

Administration, Cutaneous↗
PubMed1985

Transdermal scopolamine for peripheral vertigo (a double-blind study).

Transdermal scopolamine medication has been evaluated in 30 cases of acute peripheral vertigo. The double blind study revealed favourable effects, e.g. in Menière's disease. The best compromise between effect and side-effects was one active medication patch. The side-effects were those described for scopolamine, such as blurred vision and dryness of the mouth. Transdermal scopolamine seems to offer an alternative form of medication in acute peripheral vertigo.

Administration, Topical↗
PubMed1993

Adenosine A1 antagonists. 3. Structure-activity relationships on amelioration against scopolamine- or N6-((R)-phenylisopropyl)adenosine-induced cognitive disturbance.

The effects of a variety of adenosine A1 and A2 antagonists on N6-((R)-phenylisopropyl)adenosine (R-PIA)- and scopolamine-induced amnesias were investigated in rodents in order to clarify the role of adenosine receptors in learning and memory. Some of the selective adenosine A1 antagonists exhibited antiamnesic activities at several doses where they did not induce an increase of spontaneous locomotion. These results suggest that the blockade of A1 receptors is more important than that of A2 receptors in learning and memory. Detailed studies of structure-activity relationships of adenosine A1 antagonists in two amnesia models demonstrated that there were three types of adenosine A1 antagonists: (A) Compounds 3-5 (8-substituted 1,3-dipropylxanthines) ameliorated the shortened latency in both models. (B) Compounds 7-11 (8-substituted 1,3-dialkylxanthines) and 19-21 (imidazo[2,1-i]purin-5(4H)-one derivatives) ameliorated the shortened latency in the (R)-PIA-induced amnesia model but not in the scopolamine-induced amnesia model. (C) Compounds 14-16 ameliorated the shortened latency in the scopolamine model but not in the (R)-PIA model. Aminophenethyl-substituted compounds C did not exhibit adenosine A1 antagonism in vivo presumably due to rapid metabolism. The dramatic change in the activities of A and B could not be explained by their simple pharmacokinetic differences because both types of compounds showed clear blockade of central adenosine A1 receptors in the (R)-PIA model. 8-(3-Dicyclopropylmethyl)-1,3-dipropylxanthine (5) (KF15372) was chosen for further studies and is currently under preclinical development as a cognition enhancer.

Adenosine↗
PubMed1989

Pharmacokinetics and oral bioavailability of scopolamine in normal subjects.

The pharmacokinetics and bioavailability of scopolamine were evaluated in six healthy male subjects receiving 0.4 mg of the drug by either oral or intravenous administration. Plasma and urine samples were analyzed using a radioreceptor binding assay. After iv administration, scopolamine concentrations in the plasma declined in a biexponential fashion, with a rapid distribution phase and a comparatively slow elimination phase. Mean and SE values for volume of distribution, systemic clearance, and renal clearance were 1.4 +/- 0.3 liters/kg, 65.3 +/- 5.2 liters/hr, and 4.2 +/- 1.4 liters/hr, respectively. Mean peak plasma concentrations were 2909.8 +/- 240.9 pg/ml following iv administration and 528.6 +/- 109.4 pg/ml following oral administration. Elimination half-life of the drug was 4.5 +/- 1.7 hr. Bioavailability of the oral dose was variable among subjects, ranging between 10.7 and 48.2%. The variability in absorption and poor bioavailability of oral scopolamine indicate that this route of administration may not be reliable and effective.

Administration, Oral↗
PubMed1988

Ontogeny of activity in inbred and random-bred strains of mice: effects of scopolamine.

In Experiment 1, the activity of five inbred strains, A/J, BALB/c, C3H/HeJ, C57BL/6J, and DBA/2J, and two random-bred strains, Fullensdorf and Quackenbush, was observed at ages from 13 to 28 days. The C3H/HeJ, Fullensdorf, and Quackenbush strains exhibited a sharp increase in activity, to a peak at 17 days of age, followed by a decline at later ages. In contrast, the activity of the A/J, BALB/c, C57BL/6J, and DBA/2J mouse strains increased gradually, reaching a peak at 19 days of age. These mice displayed no decline in activity at later ages. In Experiment 2, mice from the five inbred strains and the Quackenbush strain were injected with either 0, 1.0, or 4.0 mg/kg of scopolamine before activity testing at 17, 21, or 28 days of age. Scopolamine had no effect on the activity of the various strains of mice at 17 or 21 days of age. At 28 days of age, the 4.0 mg/kg dose of scopolamine was associated with increased activity in all of the mouse strains.

Age Factors↗