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PubMed1992

Failure of d-cycloserine to reverse cognitive disruption induced by scopolamine or phencyclidine in primates.

The partial glycine agonist d-cycloserine may be of therapeutic use as a cognitive enhancer. We examined the ability of d-cycloserine (3-14 mg/kg i.m.) to reverse cognitive impairments induced by scopolamine (0.03 mg/kg) or PCP (0.25 mg/kg). There was no evidence for a dose-related improvement in visuospatial memory using retention intervals of 2,10 or 20 sec. A possible explanation for these findings is that central glycine function cannot be adequately increased using systemic administration of d-cycloserine in this dose range.

Animals↗
PubMed1987

Serum antimuscarinic activity after a single dose of oral scopolamine hydrobromide solution measured by radioreceptor assay.

Radioreceptor assay (RRA) was used to evaluate serum antimuscarinic activity in 10 healthy volunteers after a single dose of scopolamine hydrobromide (ScHBr) solution, 0.02 mg/kg, by a new oral administration method. Cardiac, antisialogogue, and subjective effects of the drug were also recorded. Although clinically useful antisialogogue and sedative effects were obtained 40 to 60 minutes after the administration of ScHBr, no reliable antimuscarinic activity was evaluated in serum samples for up to 3 hours. Clinically useful sedative and antisialogogue effects can be reached by gastrointestinal absorption of ScHBr solution.

Administration, Oral↗
PubMed1987

Oral scopolamine hydrobromide solution as an antisialagogic agent in dentistry.

Antisialagogue, cardiac, and subjective effects of oral scopolamine hydrobromide solution (ScHBr), 0.02 mg/kg total body weight, were studied in a double-blind, randomized, placebo-controlled manner with ten healthy volunteers. ScHBr was rinsed in the mouth for 5 minutes before swallowing. ScHBr reduced nonstimulated and paraffin-stimulated salivation at 40 minutes by 52% and 62%, and at 60 minutes by 81% to 80%, respectively. The heart rate decreased significantly (p less than 0.01) when compared with placebo. With the same drug dosing method, the effects of ScHBr also were tested in clinical dental examination procedures in two dental student groups. In the ScHBr group, salivation decreased by 70%, and in the placebo group, it increased by 22% as a result of mechanical stimulus. Subjective sedation and relaxation were experienced by most of the volunteers.

Administration, Oral↗
PubMed1990

Unilateral mydriasis caused by transdermal scopolamine.

Contamination of the eye after handling of a transdermal scopolamine patch may cause accidental mydriasis. A simple office test is discussed to identify this pharmacologic blockade and thereby avoid an extensive neurologic workup.

Administration, Cutaneous↗
PubMed1986

Joint cholinergic-serotonergic control of neocortical and hippocampal electrical activity in relation to behavior: effects of scopolamine, ditran, trifluoperazine and amphetamine.

Previous research has indicated that low voltage fast activity (LVFA) in the neocortex and rhythmical slow activity (RSA) in the hippocampus can result from activity in either (or both) the cholinergic corticipetal projections from the basal forebrain and the serotonergic corticipetal projections from the brainstem raphe. These inputs appear to give rise, respectively, to atropine-sensitive LVFA and RSA and atropine-resistant LVFA and RSA. The atropine-sensitive and atropine-resistant waveforms have been shown to have distinctive behavioral correlates. The present experiments extend these findings by providing dose-response data on the effects of scopolamine and Ditran on neocortical activity in relation to behavior in the rat. In addition, new evidence is presented which indicates that neuroleptic drugs reduce activity in the atropine-resistant (presumably serotonergic) inputs to the hippocampus and neocortex by an indirect action involving dopamine receptors. A single dose of d-amphetamine or apomorphine appears to increase activity in the same pathway by a similar indirect action. These findings may be relevant to the psychiatric effects of neuroleptic drugs.

Acetylcholine↗
PubMed1991

Effects of diazepam, pentobarbital, scopolamine and the timing of saline injection on learned immobility in rats.

The rat forced-swimming test (FST) is widely used for screening substances with a potential antidepressant effect. Rat immobility shown in the FST has been interpreted as "behavioral despair" and has been suggested as an animal model of human depression. In the following series of experiments, it is shown that pentobarbital and scopolamine administered immediately after the first phase, and diazepam administered 15 minutes before the first phase, behave as false positives in the FST. It is concluded that the learning-memory hypothesis seems to cope better with the behavior of rats during the FST than the "behavioral despair" hypothesis. It is also shown that the sensitivity of the FST is affected by the fact that the last saline injection, one hour before the second phase, increases the animals' mobility.

Animals↗
PubMed1990

Prospective study utilizing transdermal scopolamine in detrusor instability.

Ten patients with pure detrusor instability were treated in a prospective fashion with transdermal scopolamine. Seventy percent of patients experienced moderate to severe untoward symptoms requiring discontinuation of medication. Three of 10 patients (30%) demonstrated a subjective improvement although only 1 was able to tolerate the medication. No objective change in detrusor instability was demonstrated.

Administration, Cutaneous↗
PubMed1992

Transdermal scopolamine in prevention of post open prostatectomy bladder contractions.

In a prospective randomized double-blind study among 50 males undergoing surgery we evaluated the possible role of transdermally applied scopolamine (Scopoderm) in the prevention of post open prostatectomy bladder contraction and pain. Patients were evaluated by subjective report of their pain, urination sensation while having indwelling catheter, amount of narcotic administration, and bladder pressure measurements. No significant differences were noted with regard to the occurrence of pain or overall analgesia requirements. However, on postoperative day 2, a significant decrease in analgesia requirements was found among the treated patients. We suggest that the use of Scopoderm may lead to a reduced demand for narcotics by patients from postoperative day 2 onward.

Administration, Cutaneous↗
PubMedDate not supplied

Automatically determined effects of lithium, scopolamine and methamphetamine on motor activity of rats.

A device is described in which spontaneous motor activity of animals can be measured quantitatively in a capacitance field. By using multilevel detection in a homogeneous field the motions of the animals can be categorised according to their amplitudes and irrespective of the position of the animal in the cage. The effects of lithium ions, methamphetamine and scopolamine were assessed and compared with data in the literature.

Animals↗
PubMedDate not supplied

Scopolamine induced changes in activity and reactions to novelty.

The behavior of hooded rats was observed in an exploration box comprising novel and familiar halves following IP injections of 0.1, 0.25, 0.5, 0.75 or 1.00 mg/kg scopolamine or isotonic saline. Drug administration occurred after, rather than before, exposure to one of the alternative halves. All doses decreased reactions to the previously inaccessible novel half but decreases were greater for the 2 lowest doses. Rearing behavior was also suppressed by each dose whereas the number of apparatus cells entered (locomotion) was decreased by low doses but increased by high. The 3 behavioral measures showed declines in frequency during the course of each experimental session. However, low doses of the drug enhanced and high doses retarded these declines for rearing and cells entered. The study illustrated the difficulty in explaining data by unitary processes (such as attenuated habituation) when several behavioral indices and drug doses are employed within a single investigation.

Animals↗
PubMed1980

Scopolamine and KCl injections into the caudate nucleus. Overtraining-induced protection against deficits of learning.

To test the hypothesis that extended training of an instrumental task prevents the performance impairments seen after cholinergic and generalized blockade of caudate-putamen complex (NC) activity in animals with a relatively low degree of training, groups of rats were trained to press a lever under a continuous reinforcement schedule for 5, 15 or 25 sessions; The effects of microinjections of scopolamine and potassium chloride into the CN were then assessed. In agreement with early studies in cats, a significant deficit in performance was produced in the animals with a low or medium degree of training, while no changes in learned behavior were seen in the overtained rats. These results show that: (a) normal neural activity of the CN is essential for performance of instrumental behavior during acquisition and early maintenance stages but not after overtraining, and (b) that after extended training the encoding necessary for performance may be transferred to another neural system outside the CN.

Animals↗
PubMed1987

Differences in the acquisition process and the effect of scopolamine on radial maze performance in three strains of rats.

The acquisition process and the effect of scopolamine (SCOP) on the radial maze task were studied in 3 strains of male rats, Fischer 344 (F344), Sprague-Dawley (SD) and Wistar. The pretraining level of locomotor activity was measured and performance was quantitatively and qualitatively evaluated. The highest pretraining locomotor activity was observed in Wistar rats. In this experiment, rats were allowed to select each arm successively. The changes in the number of correct choices during the first eight selections, error choice in a trial and the total duration of a trial differed with the strain in the first 5 training sessions. Acquisition curve for F344 rats gradually rose. Wistar rats made many error choices. However, during the final 5 sessions, only the total duration of a trial differed with the strain. Wistar rats took the shortest time to finish a trial, but the number of sessions taken to acquire this task was the fewest with F344 rats, and the most with Wistar rats. The effect of SCOP differed among strains in all the above 3 indexes. Generally, the Wistar rat was the most affected by the injection of SCOP. Moreover, the change of the choice accuracy and the spatial strategy by the administration of SCOP were investigated. SD and Wistar rats showed a dose-dependent decrease in choice accuracy in the earlier selection. The spatial strategy was changed in every strain by the injection of SCOP. These findings do not support the previous finding that a high level of locomotor activity yields fast acquisition of this task or that Wistar rats are better in learning than SD, but indicates that SCOP affects not only the working memory but also the motivational factor.

Animals↗
PubMed1987

Studies on desglycinamide arginine vasopressin and scopolamine in a modified/lever-touch autoshaping model of learning/memory in rats.

Vasopressin administration has been reported to improve acquisition and retard extinction of both conditioned avoidance and food-reinforced behavioral tasks. In the present experiment the effects of a vasopressin analog (DGAVP) and scopolamine (SCOP) were tested in an autoshaped lever-touch model of learning and memory. Rats were food-deprived to 80% of original body weights and tested in modular cages which contained a retractable lever that was presented on a random interval 48 sec schedule. The lever retracted after 15 sec or when it was touched, at which time one 45 mg food pellet was delivered. Subcutaneous injection of 10 micrograms/kg DGAVP 1 hr prior to acquisition and extinction sessions did not alter responding compared to saline controls. DGAVP at doses of 10, 20, and 30 micrograms/kg also failed to affect responding in a more difficult task which included an 8 sec delay between lever retraction and reinforcement. Homozygous Brattleboro rats, which are deficient in vasopressin, did not differ from normal heterozygous littermates in the acquisition of the lever-touch response. Intraperitoneal injection of SCOP (0.1-0.8 mg/kg) 30 min prior to testing caused a dose-related impairment of acquisition compared to saline controls, but did not alter responding in animals which had previously acquired the lever-touch response. These data suggest that manipulations of vasopressin do not affect, while SCOP impairs, the acquisition of a positively reinforced lever-touch response in rats.

Animals↗
PubMed1988

Scopolamine reverses haloperidol-attenuated lever-pressing for water but not haloperidol-attenuated water intake in the rat.

The operant lever-pressing response has previously (Ljungberg, Pharmacol Biochem Behav 27: 341-350, 1987) been found to be inhibited by lower doses of haloperidol than the corresponding consummatory act, i.e., water intake. In the present study it was found that the attenuation of the lever-pressing response caused by the neuroleptic, but not the attenuation of the water intake, could be counteracted by scopolamine. The results support the notion that blockade of operant responding by low doses of neuroleptics are probably related to the extra-pyramidal side-effects of neuroleptics seen in the clinic, as both phenomena can be counteracted by anticholinergics. These results therefore conflict with the anhedonia hypothesis put forward as an explanation of the attenuating effects of neuroleptics in operant settings. The findings also have a clear bearing on the role of dopamine in feeding and drinking behavior, as the results implies that different aspects of the control of water intake (i.e., the operant vs. the consummatory phase) are governed by different mechanisms in the CNS.

Animals↗
PubMed1990

Memory following cholinergic (NBM) and noradrenergic (DNAB) lesions made singly or in combination: potentiation of disruption by scopolamine.

Groups of rats were trained on either delayed matching or nonmatching to position tasks, then divided into four subgroups and given the following bilateral lesions: (a) SHAM [vehicle injection into the nucleus basalis magnocellularis (NBM) and dorsal noradrenergic bundle (DNAB)], (b) DNAB (6-hydroxydopamine lesion of the DNAB, vehicle into the NBM), (c) NBM (quisqualic acid lesion of the NBM, vehicle into the DNAB) and (d) DUAL (neurotoxin lesions of both DNAB and NBM). Following postoperative recovery, the DUAL lesion subjects were slightly impaired, but by the seventh day of testing all groups were performing at similar levels. This strongly suggests that quisqualate lesions of the NBM are not sufficient to produce severe and lasting mnemonic disorders resembling those seen in Alzheimer's disease (AD). These data also indicate that the noradrenergic system may not be of critical importance with respect to cognition. It was reasoned that an additional anticholinergic treatment might exacerbate an underlying deficiency. All groups were injected, peripherally, with the cholinergic antagonist scopolamine (0-0.5 mg/kg). This drug dose-dependently disrupted performance in all groups. Moreover, the highest dose had a marked effect in the DUAL group, impairing performance even when no mnemonic burden was present (at zero delay). The results suggest that cholinergic NBM and noradrenergic DNAB lesions produce only transient mnemonic deficiencies. A combination of the two can be disruptive, but longer term task (or reference) memory is the primary process affected, and only under certain conditions. The implication of these findings to research concerning animal models relating to Alzheimer's disease is discussed.

Animals↗
PubMed1992

Active avoidance behavior in guinea pigs: effects of physostigmine and scopolamine.

Behavioral training of guinea pigs by conventional methods, such as used for rats and mice, appears difficult. Hence, only a few behavioral experiments with guinea pigs have been described in the literature. An active avoidance technique in an automated two-way shuttlebox is described using sound as a conditioned (CS) and a tactile stimulus (a stream of air ruffling their fur) as an unconditioned (UCS) stimulus. Acquisition is fairly rapid and reproducible. Doses of physostigmine that caused moderate blood acetylcholinesterase inhibition induced dose-dependent performance decrements. These decrements were counteracted by a sign-free dose of scopolamine.

Acoustic Stimulation↗
PubMed1993

Muscarinic and nicotinic influences on masculine sexual behavior in rats: effects of oxotremorine, scopolamine, and nicotine.

In this study, the role of cholinergic systems in the regulation of male sexual behavior was analyzed by different approaches. Both muscarinic agonists and antagonists, as well as a nicotine agonist, were administered to sexually experienced male rats. In Experiment 1, oxotremorine (OXO), a muscarinic agonist, decreased the intromission frequency and ejaculatory latency in a dose-dependent way. Moreover, an increase in ejaculatory frequency was observed. In Experiment 2, the muscarinic antagonist scopolamine (SCO) produced a dose-related impairment of sexual behavior, decreasing the percentage of sexually active males. The smaller doses of SCO delayed the initiation of sexual behavior and decreased ejaculatory frequency. In an attempt to analyze the effect of muscarinic supersensitivity on sexual behavior, in Experiment 3 a long-term blockade of muscarinic receptors (SCO for 17 days) was followed by OXO administration. Animals displayed a significant increase of mount frequency, which results in the decrease of both the hit rate and ejaculatory frequency. In Experiment 4, six doses of nicotine were acutely administered. Only the higher doses (0.4, 0.8, and 1.6 mg/kg) induced a decrease in intromission frequency, although no significant differences were found in any other parameter. These results strongly suggest that cholinergic participation in masculine sexual behavior regulation is mediated mainly through muscarinic system.

Animals↗
PubMed1993

Effects of scopolamine on the rewarding and seizure-inducing properties of amygdaloid stimulation.

The relationship between amygdaloid brain-stimulation reward and the evolution of seizure activity was evaluated in this study. Current levels that maintained optimal intracranial self-stimulation (ICSS) rates were found to be lower than the minimal current intensity required to elicit an afterdischarge (AD) from the central nucleus of the amygdala. After the ICSS session, AD thresholds (ADTs) were reduced to the same levels of current used to support ICSS. Assessment of seizure stage development during ICSS testing revealed that the emergence of early-stage epileptiform events following repeated amygdaloid stimulation suppressed ICSS performance. While administration of the antimuscarinic scopolamine did not prevent the stimulation-elicited reduction in AD thresholds, it was observed to inhibit seizure progression and increase ICSS rates. These results are consistent with the excitatory function of acetylcholine in epileptogenesis and were related to the possibility that different mechanisms underlie the rewarding and seizure-inducing properties of amygdaloid stimulation.

Amygdala↗