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PubMed1976

Effects of scopolamine on variable intertrial interval spatial alternation and memory in the rat.

A repeated measures procedure, variable intertrial interval (ITI) spatial alternation, was used to assess scopolamine effects on memory, and to compare effects of the drug on discrimination processes with effects on storage. Rats learned in two stages to press left and right levers in alternation on discrete trials separated by 5 different ITI's ranging from 2.5 to 40 s and presented in random order during the experimental session. In the first stage, alternating discrimination, alternation was controlled by a light on over the correct lever at the time of the trial; in the second stage, variable ITI spatial alternation, a centrally located panel light signalled all trials and alternation was controlled by stimuli from prior trials ('memory'). Alternation response occurrence declined moderately (but significantly) with increasing ITI duration in both the alternating discrimination and variable ITI spatial alternating discrimination and variable ITI spatial alternation stages; response occurrence was also significantly decreased by scopolamine treatment in both stages. Accuracy of alternating discrimination performance was not significantly altered by either ITI duration or scopolamine treatment. Accuracy of variable ITI spatial alternation performance on a trial varied inversely with the duration of the ITI that preceded the trial. Scopolamine treatment significantly reduced accuracy of lever pressing in variable ITI spatial alternation but did not alter the slope of the curves relating accuracy to ITI duration. These effects indicate that the drug impaired discrimination processes but did not alter memory storage.

Animals↗
PubMed1984

The effects of amphetamine and scopolamine on adjunctive drinking and wheel-running in rats.

Two groups of rats were exposed to a fixed-interval 90 s schedule of food reinforcement. One group had access to a drinking tube containing water and the second had access to a running wheel. Amphetamine (0.3-10.0 mg/kg) and scopolamine (0.1-3.0 mg/kg) were assessed for their effects on lever-pressing, adjunctive drinking and adjunctive wheel-running. Low to moderate doses of amphetamine increased overall rates of lever-pressing, whereas the highest dose decreased them. Scopolamine decreased overall lever-pressing rates in a dose-dependent manner. Both drugs changed the within-interval pattern of lever-pressing from one of increasing probability through the interval to almost constant probability throughout. Overall rates of adjunctive drinking and adjunctive wheel-running were decreased by amphetamine and scopolamine. Amphetamine failed to alter the within-interval patterns of either drinking or wheel-running in any substantial manner. The effect of scopolamine was to make the probabilities of each adjunctive behaviour more even through the interval. Although the two drugs had different actions, there was little difference in the way drinking and wheel-running were affected by each.

Amphetamine↗
PubMed1975

Effects of diazepam and scopolamine on storage, retrieval and organizational processes in memory.

The effects of intramuscular injections of diazepam (0.3 mg/kg) and scopolamine (8 mug/kg) on memory processes and subjective moods were studied in 36 volunteers. Subjects (Ss) were tested in groups of four in a double blind procedure with treatments distributed according to a Latin square design. Lists of words were presented to Ss who were then tested with an immediate free recall test prior to drug administration. Following injection delayed free recall and recognition tests were given. Subsequently two sets of lists were presented separately and tested in the same fashion. Two of the lists in the last set were composed of words falling into distinct categories. Memory was additionally analyzed by testing immediate recall of digit sequences and employing a visual recognition test. Subjective moods were evaluated with a rating questionnaire. Both diazepam and scopolamine impaired memory functions although the action of the latter drug was more pronounced and prolonged. The deficit appeared to be in the storage process leaving retrieval processes unaffected. Scopolamine in addition interfered with organizational processes. Subjectively, scopolamine also produced a larger sedative effect than diazepam.

Adult↗
PubMed1975

Dose-response effects of scopolamine on activity in an open field.

The frequency of the responses, i.e., squares entered (ambulation), rearing and grooming, were recorded over 30 min for saline, and 0.25, 1.0, 2.0 and 4.0 mg/kg scopolamine treated groups. Scopolamine produced an inverted U dose-response curve for ambulation, an increase in rearing but no effect on grooming. All three responses decreased over time; scopolamine did not attenuate this rate of habituation. There did appear a dose-related time effect. It was concluded that scopolamine may have different effects on various responses recorded simultaneously over a range of doses. The results when compared to other experiments emphasized the importance of environmental factors in determining drug effects on behaviour.

Animals↗
PubMed1981

Effects of scopolamine, pilocarpine, and oxotremorine on the exploratory behavior of two psychogenetically selected lines of rats in a complex maze.

Rats of two psychogenetically selected lines received pretest IP injections of scopolamine hydrobromide (0.25, 1.0, or 4.0 mg/kg), pilocarpine hydrochloride (3.0, 6.0, or 12.0 mg/kg) or oxotremorine sesquifumarate (0.2, 0.4 or 0.8 mg/kg) and were subsequently placed in a complex enclosed maze of the Dashiell type that included a small, central, illuminated arena. Animals receiving pilocarpine or oxotremorine injections were pretreated with methscopolamine to counter the peripheral actions of these muscarinic cholinergic agonists. Following vehicle injections, Roman High-Avoidance rats (RHA/Verh) were significantly more active, explored more maze sectors, and required less time to activate the initial 24 different photocell units uniformly distributed throughout the maze than Roman Low-Avoidance rats (RLA/Verh). Scopolamine, pilocarpine, and oxotremorine depressed locomotor activity, reduced the explored area, and increased the time required to activate the initial 24 different photocell units within this complex maze for both RHA/Verh and RLA/Verh rats. Although the doses of scopolamine injected were approximately equally effective in both rat lines (except for total maze activity), the RHA/Verh rats exhibited significant alterations in several measures of maze patrolling after treatment with the lowest dose of pilocarpine, whereas the RLA/Verh rats did not. In contrast, most of the RLA/Verh rats exhibited very pronounced tremors following treatment with the highest dose of oxotremorine, but none of the RHA/Verh rats did. These results demonstrate that manipulation of the central cholinergic system with scopolamine, pilocarpine, or oxotremorine, despite their different pharmacological mechanisms, impair maze patrolling. Furthermore, the results suggest that the two psychogenetically bred lines of rats investigated are differentially sensitive to central cholinergic manipulation with the muscarinic receptor agonists pilocarpine and oxotremorine.

Animals↗
PubMed1989

Scopolamine and benzodiazepine models of dementia: cross-reversals by Ro 15-1788 and physostigmine.

The muscarinic antagonist scopolamine and the benzodiazepine lorazepam both produce transient impairments in memory and attention in normal volunteers. These impairments can be reversed by appropriate agents such as the cholinesterase inhibitor physostigmine in the case of scopolamine or the benzodiazepine antagonist Ro 15-1788 in the case of lorazepam. In this paper we investigated the pharmacological specificity of these reversals by examining the interactions of scopolamine and Ro 15-1788 and of lorazepam and physostigmine. There was no evidence that the effects of scopolamine and lorazepam on cognitive function could be attenuated by Ro 15-1788 and physostigmine, respectively. The results are discussed in terms of pharmacological models of Alzheimer's disease.

Acoustic Stimulation↗
PubMed1994

Mecamylamine reverses physostigmine-induced attenuation of scopolamine-induced hyperactivity.

It has previously been demonstrated that the muscarinic antagonist scopolamine induces hyperactivity in rodents, which is reversed by physostigmine but not by directly acting agonists such as pilocarpine. This may suggest that non-muscarinic actions of physostigmine may be responsible for its reversal of scopolamine-induced hyperactivity. We have found, in male Wistar rats, whose activity was measured on electromagnetic detector plates, that the central nicotinic receptor antagonist mecamylamine (3 mg/kg) reverses the blockade of scopolamine-induced behavioural activation induced by physostigmine. This suggests that activation of nicotinic receptors can counteract the effects of muscarinic blockade. Interestingly, however, treatment with nicotine does not block scopolamine-induced hyperactivity, suggesting that the exogenous and endogenous ligands may have different receptor or neuronal substrates.

Animals↗
PubMed1983

Scopolamine intoxications.

Pure scopolamine intoxications are extremely rare. We treated a series of severe intoxications exclusively caused by scopolamine and due to the intentional mixing of pure scopolamine into drinks. The clinical course and therapy are reported. On the basis of our experience and a survey of literature, we found physostigmine to be an excellent antidote. The symptomatology of the patients confirms that scopolamine has a dose-related stimulant effect on the central nervous system.

Adult↗
PubMed1988

Dissociative effects of scopolamine on working memory in healthy young volunteers.

Performance on tasks of digit span, mental rotation and immediate free recall of supraspan word lists was measured before and after oral administration of 1.2 mg scopolamine or placebo to healthy young volunteers. Digit span and mental rotation were sensitive to task-specific interference from articulatory suppression and spatial tapping tasks, respectively. Neither task was affected by scopolamine when completed alone or in combination with a secondary task. A concurrent secondary task reduced immediate free recall in a nonspecific fashion (i.e., spatial tapping or articulatory suppression impaired performance equally). Scopolamine significantly reduced the number of words recalled under all conditions. The results are interpreted as evidence for selective impairment of the central executive mechanism by scopolamine without disruption of function in the articulatory loop or visuospatial scratch pad.

Adolescent↗
PubMed1988

Low dose scopolamine affects discriminability but not rate of forgetting in delayed conditional discrimination.

The effect of scopolamine on remembering was examined in a delayed conditional discrimination procedure with rats. Remembering was quantified by a negative exponential function fitted to estimates of discriminability derived from a signal detection type of analysis. This function had two parameters: a measure of initial discriminability of the sample stimuli in the absence of a memory requirement (at zero delay) and a measure of rate of forgetting. Eight rats were trained on an auditory delayed conditional discrimination task until they were showing stable performance. Each rat then received doses of 0, 0.005, 0.014, 0.042, 0.125 and 0.375 mg/kg scopolamine IP in a saline vehicle. There was a highly significant, largely linear, decrease in initial discriminability. This was obvious even at the lowest dose of scopolamine. Poorer memory, as demonstrated by an increase in b, was only apparent at the highest dose. Significant changes in per cent of correct responses were also only obtained at higher doses. These results show that initial discriminability and rate of forgetting are pharmacologically as well as theoretically independent. They suggest that the measure of initial discriminability used here is a particularly sensitive measure of at least some types of cholinergic dysfunction; and they also suggest that effects of scopolamine in other working memory tasks could be more a result of changed stimulus processing than of impairment of memorial processes.

Animals↗
PubMed1990

A comparison of the effects of scopolamine and diazepam on acquisition and retention of inhibitory avoidance in mice.

Administration of either the muscarinic antagonist scopolamine or the benzodiazepine diazepam prior to training produced a dose-dependent impairment in the retention of one-trial inhibitory avoidance training in mice. To investigate the nature of this drug effect, the effects of scopolamine and diazepam were subsequently assessed on both acquisition and retention of inhibitory avoidance using a multiple-trial, training-to-criterion procedure. The training was conducted using either continuous trials in which the mouse was free to shuttle back and forth between shock and safe compartments or discrete trials in which the mouse was moved from the shock compartment of the safe compartment at the start of each trial. In either case, training continued until the mouse refrained from crossing into the shock compartment for a specified length of time on a single trial. Scopolamine (1.0 mg/kg) administered before training significantly increased the number of trials required to attain criterion, but did not affect retention when these mice were tested 2, 16, or 28 days later. In contrast, diazepam (1.0 mg/kg) did not significantly alter the number of trials necessary to reach criterion, but impaired retention of the inhibitory response in mice trained using discrete trials. The differences in the amnestic effects of scopolamine and diazepam revealed by this detailed analysis suggest that diazepam does not impair inhibitory avoidance performance through an effect on cholinergic function.

Animals↗
PubMed1991

Non-reversal of scopolamine- or age-related EEG changes by ondansetron, methysergide or alaproclate.

The present studies investigates the effects of a 5HT3-antagonist (ondansetron: 0.01, 0.1, 1, 10 micrograms), a 5HT2-antagonist (methysergide: 2, 10, 20 mg/kg) and a serotonin uptake inhibitor (alaproclate: 2, 10, 20 mg/kg) on the neocortical electrical activity of young scopolamine-treated and aged rats. The scopolamine (0.2 and 0.8 mg/kg)-induced increase in EEG spectral components was not reversed by ondansetron, methysergide or alaproclate. The scopolamine (0.8 mg/kg)-induced EEG amplitude increase reversing potency of a subthreshold dose of the muscarinic agonist pilocarpine (2 mg/kg) was not potentiated by ondansetron, methysergide or alaproclate. A higher dose of pilocarpine (10 mg/kg) reversed scopolamine-induced EEG slowing. Age-related increase in high voltage spindles (HVS) was not alleviated by either ondansetron, methysergide or alaproclate. The HVS activity stabilizing effect of pilocarpine (2 mg/kg) was not enhanced by ondansetron, methysergide or alaproclate. These results suggest that the serotonergic agents investigated could not alleviate cortical cholinergic activation deficit and once again implicate the role of cholinergic system in both the neocortical electrical activation and age-related cortical electrical arousal deficit.

Aging↗
PubMed1990

Scopolamine effects on memory, language, visuospatial praxis and psychomotor speed.

Scopolamine hydrobromide was administered by subcutaneous injection to 30 young subjects in a dose of 0.22 mg/70 kg, 0.43 mg/70 kg, or 0.65 mg/70 kg. Treatment effects were compared to placebo on an extensive cognitive assessment battery. Almost all tests in the battery had been previously administered to Alzheimer's disease patients and nondemented elderly subjects. Scopolamine produced deficits on tests of verbal recall, visuospatial recall, visual recognition memory, visuospatial praxis, visuoperceptual function, and psychomotor speed. Immediate memory, language function, object sorting, and frequency of intrusion errors were unaffected. The low dose of scopolamine produced some peripheral anticholinergic signs but did not affect the cognitive measures. The results support the conclusion reached in previous studies that the cognitive profile of scopolamine-injected young subjects is more similar to that of the nondemented elderly than to that of Alzheimer's disease patients.

Adolescent↗
PubMed1994

5-HT1A receptor agonists improve the performance of normal and scopolamine-impaired rats in an operant delayed matching to position task.

A series of experiments examined the effects of 5-HT1A ligands alone and in combination with the muscarinic antagonist scopolamine on short term working memory in the rat. The behavioural paradigm was a discrete trial, operant delayed matching to position task, with delays of 0, 5, 15 and 30 s. The 5-HT1A ligands tested were the full agonist, 8-OH DPAT (0, 0.1, 0.3 and 1 mg/kg), the partial agonist, ipsapirone (0, 1, 3 and 10 mg/kg), and the purported antagonist, NAN 190 (0, 1, 2, and 4 mg/kg). 1-PP (0, 0.1, 0.3, 1 mg/kg), the major metabolite of ipsapirone, was also tested. The lowest dose of 8-OH DPAT significantly improved matching accuracy at the longest delay, whereas the highest dose impaired matching accuracy and increased the latency to respond. Ipsapirone also significantly improved the accuracy of performance at a dose of 3 mg/kg, but the doses of 1 and 10 mg/kg did not significantly affect performance. NAN-190, at the highest dose tested (4 mg/kg), impaired matching accuracy, whereas the two lower doses did not significantly affect performance. The highest dose also increased the latency to respond. 1-PP had no effect on performance. Scopolamine HBr (0.14 mg/kg) caused a delay dependent impairment in matching accuracy, and had no effect on missed trials or the latency to respond. Low doses of 8-OH DPAT (0.1 and 0.3 mg/kg) significantly attenuated the scopolamine induced accuracy impairment, whereas 1 mg/kg 8-OH DPAT potentiated the impairment. Ipsapirone (3 mg/kg) also significantly improved the performance of scopolamine impaired rats.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Comparison of error patterns produced by scopolamine and MK-801 on repeated acquisition and transition baselines.

An understanding of the differential role of cholinergic and glutaminergic systems may be limited by the failure to move the analysis of learning impairments beyond an assessment of changes in overall accuracy. This paper reports the results of two studies in which the effects in rats of scopolamine (0.5-3.0 mg/kg IP), a cholinergic antagonist, and MK-801 (0.05-0.3 mg/kg IP), an NMDA-receptor antagonist, were compared in two different repeated learning procedures and the nature of the underlying error patterns produced by each was evaluated. The first study examined drug effects upon a repeated sequence acquisition procedure and found that while both drugs decreased overall accuracy in a dose-dependent manner, the predominant error pattern varied significantly with drug; scopolamine primarily produced skipping errors within the sequence, whereas MK-801 more prominently increased perseveration on the first and second members of the sequence. In the second study, which used a repeated transition procedure, both drugs again significantly decreased overall accuracy in a dose-dependent manner, but no consistent differences in error patterning produced by the drugs were observed. Thus, while both cholinergic and NMDA systems play a role in learning, the behavioral processes underlying the changes in overall accuracy may differ, as indicated by the differential patterns of errors produced by scopolamine and MK-801 in the repeated acquisition baseline. Furthermore, the observed differences in the underlying behavioral processes of scopolamine and MK-801 in the repeated acquisition but not on the repeated transition procedure suggest that each of the two drugs may affect more than one of the variables controlling behavior, with the relative impact of drug-related changes in controlling variables depending upon the operative contingencies of the learning task.

Animals↗
PubMed1992

Effects of physostigmine and scopolamine on rats' performances in object-recognition and radial-maze tests.

The effects of physostigmine and scopolamine were evaluated on working memory of rats in object recognition and radial-maze tests. Three doses of physostigmine hemi-sulfate (Phys: 0.05, 0.10 and 0.20 mg/kg), five doses of scopolamine hydrobromide (Scop: 0.125, 0.25, 0.5, 1.0 and 2.0 mg/kg), and one dose of scopolamine methylbromide (Mscop: 2.0 mg/kg) were used. In object recognition test, rats were submitted to three or four intertrial delay conditions (1-min, 15-min and either 60-min or 24-h). The higher doses of Scop (1.0 and 2.0 mg/kg) in 1-min and 15-min delay and of Phys (0.20 mg/kg) in 1-min delay impaired discrimination between new and familiar objects. Mscop impaired discrimination between objects in 60-min but not in 1-min and 15-min delay. This effect may be state dependent. Radial-maze learning was impaired by the lower doses of scopolamine (0.25 and 0.50 mg/kg) which had no effect in object recognition test. These results show that in our conditions, object recognition is less sensitive than radial-maze test to cholinergic drugs.

Analysis of Variance↗
PubMed1992

Effects of intra-hippocampal scopolamine injections in a repeated spatial acquisition task in the rat.

The involvement of hippocampal cholinergic synapses in spatial discrimination learning was evaluated by locally administering scopolamine into the hippocampus. Sixteen 16-month-old male Lewis rats received bilaterally implanted cannulae aimed at the dorsal part of the hippocampus. The rats were trained on a repeated acquisition test in the Morris water-escape task. In this procedure the invisible platform is randomly moved from day to day to one of four possible locations. Thus, the rat has to learn to localize the platform from day to day. On each day the rats received four pairs of trials. Scopolamine injections (35 micrograms in 1 microliter per hippocampus) were given to one group (n = 8) on days 5 and 7. On days 6 and 8 all rats received saline injections. Place learning was retarded in the scopolamine-treated rats during the first swims of pairs of trials. During second swims the scopolamine-treated rats showed a general performance deficit, indicating that first and second swims were differentially affected. The data support the hypothesis that cholinergic neurotransmission in the dorsal hippocampus is involved in spatial learning processes.

Analysis of Variance↗
PubMed1993

The interaction of L-deprenyl and scopolamine on spatial learning/memory in rats.

L-Deprenyl, a specific MAO-B inhibitor, has been reported to improve learning/memory in some cognitive tests in aged rats. The present study investigated whether L-deprenyl could alleviate the spatial learning deficit induced by muscarinic blockade and aging in OFA rats. Scopolamine (0.25 mg/kg) impaired the acquisition of a water maze task in adult rats and increased their swimming speeds. L-Deprenyl (0.25 mg/kg, 14 days) had no effect on water maze performance in saline treated adult rats, but markedly alleviated the learning deficit induced by scopolamine and increased the time and distance of swimming in the training quadrant when the platform was removed (spatial probe trial). L-Deprenyl partly reduced the effect of scopolamine on speed of swimming. Nevertheless, administration of l-deprenyl (0.25 mg/kg, 14 days) had no effect on spatial learning/memory in aged rats. We suggest that the l-deprenyl-scopolamine interaction in the water maze test may be considered as a premise for further investigations of l-deprenyl as cognition enhancer.

Aging↗