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PubMed1991

[Effects of scopolamine upon delayed radial-arm maze performance in rats].

Behavioral impairment induced by the muscarinic anticholinergic drug, scopolamine (SCP) has been widely used to make preclinical evaluation of nootropic drugs. To further investigate the disruptive effect of SCP on memory-related behavior, male Wistar-Imamichi strain rats were tested in the 8-arm radial maze task with a delay interval between choices 4 and 5. In this task, the animals were first allowed to obtain 4 food rewards out of 8 arms and then removed from the maze. They were replaced on the maze to collect the remaining 4 pellets after a delay interval, during which they were kept in their home cages. In experiment 1, a 1-6 hr delay interval was imposed. SCP (0.5 mg/kg, i.p.) was administered immediately after choice 4. In experiment 2, a delay interval was always 4 hr, but SCP was administered 0-2 hr after choice 4. In both experiments, SCP significantly reduced the number of correct choices in choices 5-8, but did not show any effects depending on delay intervals or drug-administration time. These results suggest that the performance deficits induced by SCP might be due to its effects on the primary stage of information processing rather than those on the consolidation or storage process of memory.

Animals↗
PubMed1990

Cross interaction between methamphetamine and scopolamine by means of ambulatory activity in mice.

Interaction between methamphetamine (MAP; 1 and 2 mg/kg, s.c.) and scopolamine (SCP; 0.5 and 2 mg/kg, s.c.) was investigated by means of ambulatory activity in mice of the dd strain. The single administration of MAP and SCP increased the ambulatory activity in a dose-dependent manner. The repeated administration of SCP, 5 times at intervals of 3-4 days, elicited a tolerance to its ambulation-increasing effect. The SCP-experienced mice showed no marked change in their sensitivity to the ambulation-increasing effect of MAP. However, when MAP was additionally administered, these mice showed a reverse tolerance to MAP. Such repeated administration of MAP was effective for attenuating the SCP-tolerance. On the other hand, the repeated MAP administration produced not only reverse tolerance to MAP itself but also cross reverse tolerance to SCP. However, as observed in the drug-naive mice, the MAP-experienced mice also exhibited tolerance to the additionally administered SCP. The repeated SCP administration scarcely modified the acquired MAP-reverse tolerance. The present results suggest that a cross reverse tolerance from MAP to SCP, but not from SCP to MAP, is developed in this mouse strain. It is also suggested that the reverse tolerance to MAP and tolerance to SCP appear regardless of the pretreatment of SCP and MAP, respectively, and that the reverse tolerance to MAP is well-maintained.

Animals↗
PubMed1993

Improving effects of FG-7080, a serotonin reuptake inhibitor, on scopolamine-induced performance deficits of memory tasks in rats.

A novel serotonin reuptake inhibitor, (-)trans 4-(4-fluorophenyl)-3-(4-methoxyphenoxy-methyl)piperidine hydrochloride (FG-7080), was investigated for its effects on scopolamine-induced impairments in memory tasks of rats. In the radial-arm maze task, FG-7080 (3 mg/kg, p.o.) improved the impaired performance. FG-7080 (1 mg/kg, p.o.) administered before the acquisition trial reduced the acquisition deficits in the passive avoidance task. Thus, the compound showed improving effects in the appetitive and aversive memory tasks. These findings suggest that FG-7080 may ameliorate the cognitive impairments caused by the cholinergic dysfunction.

Animals↗
PubMed2000

Effect of intracerebroventricular administration of soybean lecithin transphosphatidylated phosphatidylserine on scopolamine-induced amnesic mice.

The effect of intracerebroventricularly administered soybean lecithin transphosphatidylated phosphatidylserine (SB-tPS) on memory impairment was evaluated by a passive avoidance task. SB-tPS significantly prolonged the step-through latency induced by scopolamine treatment as in our previous report where SB-tPS was orally administered. The same doses of soybean phosphatidylcholine were ineffective. This result indicates that SB-tPS can act on the brain without any peripheral modification.

Amnesia↗
PubMed2001

Ameliorative effects of azaindolizinone derivative ZSET845 on scopolamine-induced deficits in passive avoidance and radial-arm maze learning in the rat.

Effects of ZSET845 (3,3-dibenzylimidazo[1,2-a]pyridin-2-(3H)-one), a newly synthesized cognitive enhancer, and donepezil and tacrine on the scopolamine-induced cognitive deficits in rats were examined in passive avoidance and radial-arm maze tasks. ZSET845 (0.01 mg/kg) showed a greater ameliorative effect than donepezil (0.1 mg/kg) or tacrine (1 mg/kg) in the passive avoidance task. In the radial-arm maze task, ZSET845 (0.1 mg/kg) also showed a greater effect than donepezil (10 mg/kg) or tacrine (10 mg/kg). ZSET845 induced an increase in the choline acetyltransferase (ChAT) activity in the hippocampus, suggesting that the ameliorative effects of ZSET845 are related to the increase in the ChAT activity in the hippocampus.

Alzheimer Disease↗
PubMed2006

Memory-enhancing effect of a supercritical carbon dioxide fluid extract of the needles of Abies koreana on scopolamine-induced amnesia in mice.

Abies koreana Wilson (A. koreana) is a shrub or broadly pyramidal evergreen tree endemic in the mountainous regions of South Korea. We obtained the essential oil (EO) from alpine needle leaves of A. koreana by the supercritical fluid extraction (SFE) method. EO was analyzed by gas chromatography-mass spectrometry (GC-MS), and 68 compounds were identified constituting 95.66% of the oil. The major components were elemol (11.17%), terpinen-4-ol (9.77%), sabinene (8.86%), 10(15)-cadien-4-ol (7.16%), alpha-terpineol (6.13%), alpha-pinene (6.07%) and gamma-terpinene (4.71%). To investigate the memory-enhancing effects, we conducted a passive avoidance test using a scopolamine (1 mg/kg, ip)-induced amnesia mouse model. A peritoneal injection of EO from A. koreana (100 mg/kg) showed a memory enhancing effect of 72.7% compared with the control. These results suggest that EO of A. koreana may be a useful therapeutic agent against such amnesia-inducing diseases as Alzheimer and vascular dementia.

Abies↗
PubMed2001

Effects of acamprosate and scopolamine on the working memory of rats in a three-panel runway task.

The aim of this study was to evaluate the effect of treatment with single (1x) and multiple (10x) doses of the anti-craving compound acamprosate (AC, calcium acetyl homotaurinate) on working memory in rats, using in a three-panel runway test. We measured tasks after the animals were treated with AC (500 mg/kg/d, i.p.); scopolamine (SC, 0.5 mg/kg/d, i.p.), a cholinergic muscarinic receptor antagonist; or both drugs concomitantly (ACSC), either for 1 day (1x) or daily for 10 consecutive days (10x). Neither 1x not 10x AC alone had a significant effect on working memory task performance, whereas treatment with SC alone had a significantly negative effect on the ability of the rats to complete the tasks. Rats receiving ACSC performed better than those receiving SC alone, making fewer errors and displaying shorter latency, similar to the performance of the control group. These observations support the hypothesis of an indirect involvement of AC in the cholinergic system.

Acamprosate↗
PubMed2002

Excitotoxic median raphe lesions aggravate working memory storage performance deficits caused by scopolamine infusion into the dentate gyrus of the hippocampus in the inhibitory avoidance task in rats.

The interactions between the median raphe nucleus (MRN) serotonergic system and the septohippocampal muscarinic cholinergic system in the modulation of immediate working memory storage performance were investigated. Rats with sham or ibotenic acid lesions of the MRN were bilaterally implanted with cannulae in the dentate gyrus of the hippocampus and tested in a light/dark step-through inhibitory avoidance task in which response latency to enter the dark compartment immediately after the shock served as a measure of immediate working memory storage. MRN lesion per se did not alter response latency. Post-training intrahippocampal scopolamine infusion (2 and 4 microg/side) produced a more marked reduction in response latencies in the lesioned animals compared to the sham-lesioned rats. Results suggest that the immediate working memory storage performance is modulated by synergistic interactions between serotonergic projections of the MRN and the muscarinic cholinergic system of the hippocampus.

Animals↗
PubMed1985

Transdermal hyoscine (Scopolamine). A preliminary review of its pharmacodynamic properties and therapeutic efficacy.

Hyoscine (scopolamine) is a competitive inhibitor of the muscarinic receptors of acetylcholine and it has been shown to be one of the most effective agents for preventing motion sickness. However, a relatively high incidence of side effects and a short duration of action has restricted the usefulness of this agent when administered orally or parenterally, and to counter this a novel transdermal preparation of hyoscine has been developed. Pharmacokinetic studies indicate that this new method for administering hyoscine controls the absorption process and the rate of drug entry into the systemic circulation over an extended period (72 hours), providing a means of delivery which is similar to a slow intravenous infusion. However, recent evidence suggests that the response to transdermal hyoscine treatment is variable and this may reflect pharmacokinetic differences between individuals. Controlled therapeutic trials have indicated that a single transdermal hyoscine patch is significantly superior to placebo and oral meclozine (meclizine) in preventing motion sickness. Trials comparing transdermal hyoscine with oral dimenhydrinate have failed to establish any significant differences in efficacy between the 2 drugs in small numbers of subjects, although there was always a more favourable trend towards the transdermal system. In patients with acute vertigo, transdermal hyoscine and oral meclozine were equally efficacious and both were significantly better than placebo in reducing the number of attacks of vertigo. Although transdermal hyoscine has been associated with a lower incidence of side effects than orally or parenterally administered hyoscine hydrobromide, adverse systemic effects have still been frequently reported. Most commonly cited have been dry mouth, drowsiness and impairment of ocular accommodation, including blurred vision and mydriasis (some ocular effects reported may be due to finger-to-eye contamination). Adverse central nervous system (CNS) effects, difficulty in urinating, rashes and erythema have been reported only occasionally. Thus, preliminary evidence suggests transdermal hyoscine may offer an effective and conveniently administered alternative for the prevention of motion-induced nausea and vomiting in certain situations. However, the duration of its clinical effectiveness, and its relative efficacy and tolerability compared with other agents needs to be confirmed in a few additional well-designed studies.

Administration, Topical↗
PubMed1988

Behavioral effect of scopolamine in cats.

An ethological study was performed on a colony of cats. Their spontaneous behavior was observed following the chronic administration of scopolamine hydrobromide (0.3 mg/kg/day). Forty-four behavioral units grouped under four categories--resting postures, individual actions, grooming and social interactions--were coded. A general decrease of the frequency of the tested behaviors was observed; this was particularly true of those behaviors in response to individual or social stimulus of an affiliative or agonistic type. The results were consistent with former reports in other species suggesting the changes in attention underlie this lack of response.

Animals↗
PubMed1994

Efficacy comparison of scopolamine (SCP) and diazepam (DZ) against soman-induced lethality in guinea pigs.

Diazepam (DZ) and scopolamine (SCP) are known to be beneficial when each is used in combination with atropine (AT) + oxime therapy against intoxication by soman, but the efficacy of each might be expected to vary with the dosage of AT. Thus the therapeutic efficacy of SCP (5 doses; 0-0.86 mg/kg) versus DZ (5 doses; 0-5 mg/kg), when used in conjunction with AT (3 doses; 0.5-8 mg/kg) + 2-PAM (25 mg/kg) therapy, was tested 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 lethality and the AT/DZ or AT/SCP dosages. Results show that within the indicated dose ranges used, the efficacy of SCP is not dependent on the presence of AT, whereas AT is needed for DZ to maintain the lowest probability of death. These findings suggest that in guinea pigs SCP could supplement AT or replace DZ as therapy against nerve agent intoxication.

Animals↗
PubMed1997

Antagonism of soman-induced convulsions by midazolam, diazepam and scopolamine.

The effects of midazolam (MDZ), diazepam (DZ) and scopolamine (SCP) therapies on soman-induced electrocorticogram (ECoG) and biceps femoris electromyogram (EMG) activities and brain lesions were assessed in male rats. Animals received pyridostigmine (26 micrograms/kg, im) 30 min before soman (87.1 micrograms/kg, im) followed by therapy consisting of atropine (1.5 mg/kg) admixed with 2-PAM (25 mg/kg, im) 1 min later; MDZ (0.5 mg/kg), DZ (1.77 mg/kg) or SCP (0.43 mg/kg) was administered im at 1 min after the onset of convulsions (CVs). Typically, within 5 min after soman the ECoG profile changed to a full-blown, spike-and-dome epileptiform (SDE) pattern followed by CVs and increased amplitude of EMG activity. Treatment with SCP restored ECoG and EMG profiles by 30 min. At 2 hr after exposure only 1 animal demonstrated a slight abnormality in ECoG activity which was normal at 24 hr. Similarly, DZ and MDZ restored EcoG and EMG profiles by 30 min; however, in contrast to SCP, 83% of the animals demonstrated reappearance of SDE 2 hrs after soman. SCP therapy also enabled rats to move about in their cages by 30 min post treatment. In contrast, DZ- and MDZ-treated rats remained incapacitated as late as 2 hr post-exposure. Animals were euthanized at 24 hr, and the extent of soman-induced brain lesions was determined by light microscopic analysis. When present, brain lesions were minimal in SCP-treated rats. The mean brain lesion scores across all experimental conditions ranked as follows: soman control > MDZ > DZ > or = SCP = saline control. These observations suggest that SCP may be highly effective in severe soman intoxication.

Animals↗
PubMed2002

Behavioural responsiveness to amphetamine or scopolamine following repeated exposure to chlorphenvinphos in rats.

A number of reports indicate that exposure to organophosphates (OPs), inhibitors of acetylcholinesterase (AChE), may result in long-lasting neurobehavioural alterations suggestive of an increased cholinergic tone. It is known that rats with cholinergic hyperreactivity are behaviourally hyposensitive to cholinergic antagonists and dopaminergic agonists. The purpose of the present study was to find out whether a similar trait would develop in rats exposed to chlorphenvinphos (CVP), an OP pesticide, in the past. The rats were given ten daily i.p. injections of CVP at doses of 0.5 mg/kg (group P-0.5) or 1.0 mg/kg (group P-1.0). The locomotion stimulating effect of i.p. injection of 1.0 mg/kg amphetamine (AMPH), or 0.7 mg/kg scopolamine (SCOP), was assessed on postexposure day 21 (group P-0.5) or 42 (group P-1.0), i.e. after a time sufficient for AChE recovery. The assessment revealed that in group P-1.0 the behavioural response to AMPH and SCOP was significantly depressed. In rats of the P-0.5 group, however, the behavioural response to each of the drugs was increased. The results suggest that, depending on the exposure level, contrasting alterations in some neurotransmitter systems may be induced by repeated exposure to CVP.

Amphetamine↗
PubMedDate not supplied

[The effect of scopolamine on the spatial organization of rat cortical potentials].

The influence of scopolamine (1 mg/kg, i.p.) on the spatial organization of the neocortical electrical activity was studied in rats. A decrease in the spectral power and coherence of brain potentials in the range of the dominant theta-rhythm peak (6.00-7.25 Hz) and their increase in the adjacent low-frequency band were observed. Both indices were decreased in the wide beta band (19.00-30.00 Hz). The described changes took place over the whole areas of the right hemisphere and parieto-temporal region of the left hemisphere. The obtained results are discussed with respect to the role of the cholinergic brain system in the higher nervous activity.

Animals↗
PubMedDate not supplied

[Is "scopolamine-induced amnesia" in rats the result of state-dependent learning?].

The effects of a single and repetitive administration of m-cholinoblocker scopolamine (Sc) to male rats on retention of step-through passive avoidance (PA) or active avoidance (AA) in a shuttle-box were compared. In case of PA Sc (1 mg/kg) was injected i.p. only 30 min before training, only 30 min before testing, or both before training and before testing. In case of AA Sc (0.5 mg/kg/day) was injected i.p. only 15 min before each training session or both before training and before testing (44 days after achievement of learning criterion). The PA and AA retention were impaired only in the experiments, where the drug was administered before training, but did not differ from control, when Sc was injected twice. The Sc-induced amnesia (like many other cases of memory deficits) is suggested to be a manifestation of state-dependent learning. Similarity between the brain state during memory consolidation and during the retention test is necessary for recollection.

Acoustic Stimulation↗
PubMed2000

Serial position effect and selective amnesia induced by scopolamine in mice.

Mice were trained to run through a maze with six gates, each consisting of three doors--two locked and one unlocked. They learned to choose a correct (unlocked) door at the gates close to the beginning and end better than in the middle, showing the primacy and recency effects of serial learning. A low dose of scopolamine unexpectedly enhanced the primacy effect, while a high dose impaired learning in general. The enhancement of the primacy effect can be explained in terms of reduction of retroactive interference.

Amnesia↗
PubMed2000

Vertical nystagmus in normal subjects: effects of head position, nicotine and scopolamine.

We measured gaze stability in darkness of four normal humans using the search coil technique. Subjects were tested first with their heads erect, and then with their heads positioned 180 degrees upside-down. In each position, subjects held their head stationary for one minute, and then actively performed pitch rotations for 20 sec. All subjects showed sustained chin-beating nystagmus in the upside-down position. Each subject showed a significant increase of slow-phase velocity directed towards their brow after 40 sec in the inverted versus erect position. Pitch head rotation had little effect on subsequent nystagmus, except for transient reversal in one subject. The sustained changes of vertical eye drifts induced by 180 deg change of head position suggest that otolithic factors may contribute to vertical nystagmus in normals. The subjects were retested after wearing a nicotine patch for 2 hours. In three subjects, nicotine induced brow-beating nystagmus; adopting a head-hanging position increased this nystagmus in two subjects. In a third session, subjects were tested after wearing a scopolamine patch for 2 hours; results were generally similar to the control condition. We conclude that normal subjects may show chin-beating ("downbeating") nystagmus in a head-hanging position in darkness, reflecting a normal, physiological change in otolithic inputs brought about by the head orientation.

Adult↗