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PubMed1995

Effects of thioperamide, a histamine H3-receptor antagonist, on a scopolamine-induced learning deficit using an elevated plus-maze test in mice.

We examined the effects of thioperamide and (R)-alpha-methylhistamine, a histamine H3-receptor antagonist and an agonist, respectively, on a scopolamine-induced learning deficit using an elevated plus-maze test in mice. Thioperamide alone slightly improved the learning deficit induced by scopolamine, and pretreatment with zolantidine, a histamine H2-receptor antagonist, significantly enhanced the effect of thioperamide in this test. (R)-alpha-Methylhistamine, pyrilamine, ketotifen, terfenadine, and zolantidine alone at the doses tested had no effect. Moreover, the improvement by thioperamide plus zolantidine was antagonized by pretreatment with histamine H1-receptor antagonists such as pyrilamine or ketotifen, but not by terfenadine. Thus, thioperamide improved the scopolamine-induced learning deficit through central histamine H1 receptors in mice. The present results supported the hypothesis that histamine may play an important role in learning and memory.

Animals↗
PubMed1986

Antistereotype effects of ceruletide and some neuroleptics differentiated by interactions with clonazepam, muscimol, scopolamine and clonidine.

Compulsive gnawing was produced in mice by administration of either methylphenidate or (after sensitizing pretreatment with the neuroleptic, tetflutixol) apomorphine. Drugs which antagonise stereotypy, such as ceruletide (CER, a sulphated decapeptide related to cholecystokinin octapeptide), haloperidol, zuclopenthixol and fluphenazine were applied in equipotent doses (reducing stereotypy by 80%). Clonazepam, muscimol, clonidine and scopolamine (but not methylscopolamine) antagonized to a different extent the antistereotype effect of ceruletide and the neuroleptics. The ED50s for clonazepam and other drugs, were determined; clonazepam had the greatest potency. Regarding the antagonism of the antistereotype effect, ceruletide was similar to but by no means congruent with haloperidol. The antagonism of the antistereotype effect was specific because other effects of ceruletide and cholecystokinin octapeptide (inhibition of exploratory rearing activity, ptosis, antinociception, hypothermia) were not antagonized by clonazepam and only weakly modified by scopolamine. Methylscopolamine was ineffective throughout, indicating a central site for the mechanism of the actions studied of scopolamine. In conclusion, the antistereotype effect of ceruletide is different from that of conventional neuroleptic drugs and functionally independent of other behavioural effects of the cholecystokinin-like peptides.

Animals↗
PubMed1985

Development of mouse activity, stimulus reactivity, habituation, and response to amphetamine and scopolamine.

Twenty-four litters of non-inbred Swiss-derived mice were used to study the development of locomotion and tendency to approach a novel object in an open field, as well as the effects of dl-amphetamine sulfate and scopolamine hydrochloride (1 or 2 mg/kg IP). Brief (7 min) tests repeated for three consecutive days were preferred in order to obtain information on between-session habituation. Animals tested on days 14-16 showed low levels of activity without changes in successive sessions. In contrast, an adult-like pattern with a high initial activity and marked between-session decrements prevailed on days 21-23 and 28-30. Dl-amphetamine elevated activity only on days 14-16, while scopolamine produced hyperactivity and impaired habituation only on days 21-23 and 28-30. Latency to approach a novel object by untreated animals showed a substantial reduction between the end of the second week and subsequent developmental stages. This went hand in hand with an appearance of latency increases after dl-amphetamine treatments, while an opposite trend in the scopolamine data failed to reach statistical significance. Activity tests in a photocell apparatus at 61-72 days (without prior treatment) showed a reduction of locomotion relative to the level measured in animals from other litters raised in parallel and not subjected to early testing. Overall, the present data and those of the literature indicate that some developmental phenomena in small rodents are relatively insensitive to a variety of organismic, environmental, and test factors, while others (e.g., inverted U-shaped activity trends and successive modifications of the amphetamine profile) depend on complex interactions between several variables.

Age Factors↗
PubMed1986

Scopolamine-induced deficits in acquisition of a complex spatial learning.

The role of scopolamine was studied in a complex spatial orientation task. The procedure involved an increasing difficulty of the task: at the pretraining stage a cue (box) was placed at the reinforcement spot and the animal could give a correct response by adopting either a cue-strategy or an orientation response (i.e., go to the arm on the right of a visual landmark). In the subsequent spatial training, the box was removed, so that the orientation response was the only correct one. Results show that scopolamine-injected animals are able to use a cue-strategy but are unable to acquire a spatial orientation strategy: this more complex task asks for more time and for more sustained attention. When the response is already partly acquired, scopolamine has less effect. The cholinergic system would thus be involved in the quality or even the complexity of the response rather than in the retention itself. Though a state-dependent effect may not be excluded, it by itself cannot explain the observed differences. Finally, an impairment of the maintenance of attention could be responsible for the deficits observed in the acquisition of the complex task.

Animals↗
PubMed1989

Scopolamine impairs response-to-change based on distal cues in the rat.

The effect of a scopolamine injection (1 mg/kg, IP) on response-to-change behavior was investigated in two experiments. After exploration of a T-maze with one arm black and the other white (Trial 1), rats were tested with both arms either black or white (Trial 2). Experiment 1 revealed that the opportunity to make body turns into the arms did not help scopolamine-injected rats to locate the changed arm after visual exploration of the arms during Trial 1. Saline-injected animals chose the changed arm. In Experiment 2, rats were allowed to move freely into the arms during Trial 1. During Trial 2, they were tested either from the same start as that used during Trial 1 or from a different start 180 degrees from the original start. While scopolamine-injected animals reacted appropriately to the change when tested from the same start, they were impaired when tested from the opposite start. In both conditions, saline-injected animals chose the changed arm. These results, together with others, support the notion that the cholinergic system plays a crucial role in the processing of distal information.

Animals↗
PubMed1989

Scopolamine inhibition of lordosis in naturally cycling female rats.

Cholinergic antagonists, such as scopolamine, atropine, and hemicholinium-3, have been found previously to inhibit lordosis in ovariectomized rats primed with estrogen and progesterone. The present study further examined this effect using intact cycling female rats. Cycling was determined by daily monitoring of sexual behavior and vaginal cytology. In the first experiment, intraventricular administration of the muscarinic receptor blocker, scopolamine, was found to significantly inhibit lordosis behavior during natural estrus (10 or 20 micrograms bilaterally). In the second experiment, systemic administration of scopolamine was also found to significantly inhibit lordosis behavior during natural estrus (4 mg/kg, IP). Administration of the cholinergic antagonist did not significantly interrupt cyclicity patterns. These results indicate that central cholinergic muscarinic systems contribute to the regulation of lordosis during natural behavioral estrus in intact female rats.

Animals↗
PubMed1992

Delayed matching-to-sample performance by rats in a new avoidance-motivated maze: response to scopolamine and fimbria-fornix lesions.

A new avoidance-motivated detour-maze in which memory for an immediately preceding sample event could be assessed was evaluated by testing seven 6-month-old male F-344 rats with a delayed matching-to-sample (DMTS) paradigm. Rats first received extensive pretraining with this paradigm over several months and after a minimum of 1,390 choice-trials demonstrated great proficiency in this maze. Studies were then conducted to establish cholinergic and hippocampal involvement in the DMTS task by using drug manipulations (scopolamine and physostigmine), and after lesions to the fimbria-fornix (FF) pathway. A high dose (1.0 mg/kg) of scopolamine but not a low dose (0.3 mg/kg) significantly interfered with choice accuracy as measured by errors and trials to criterion; physostigmine (0.01 and 0.03 mg/kg) had no significant effect; and fimbria lesions significantly disrupted both choice accuracy and runtime performance. Disruption was most pronounced on difficult problems (different paths to the goal). After lesions only, considerable within-trial perseverative errors occurred during the early postlesion weeks on four difficult problems from among the 18 tested. Results were discussed in terms of (a) specificity of this disruption, (b) indications of proactive interference effects, and (c) the movement-related excitation component of maze learning. The present results accord with earlier findings of disruption by scopolamine and FF lesions in a 14-unit T-maze, both mazes having similar performance requirements of shock avoidance and multiple 90-degree turns along the paths to the goal. The present results affirm that this new detour maze provides a viable approach for assessing cognitive performance in a within-subject design and thereby offers new possibilities for testing various aspects of cognitive processing, particularly for aged rodent models, in a complex aversive situation.

Aging↗
PubMed1994

Reversal of extinction by scopolamine.

The aim of this experiment was to determine the effects of muscarinic blockade on extinction of passive avoidance conditioning. Rats were trained with a foot shock of 2.5, 3.0, or 6.0 mA and were tested for retention for 8 weeks (once weekly). Five minutes before the seventh test they were injected with 8 mg/kg scopolamine. The groups that had been trained with 2.5 and 3.0 mA showed extinction, which was reversed by the scopolamine; the overreinforced group (6.0 mA) did not show extinction and the scopolamine did not alter the conditioned response. The data support the hypothesis that extinction represents the learning of a new response sustained by a set of cholinergic neurons, different from that which mediated original passive avoidance learning.

Acetylcholine↗
PubMed1996

The muscarinic acetylcholine antagonist scopolamine impairs short-distance homing pigeon navigation.

The present study employed intramuscular (i.m.) injections of the acetylcholine (ACh) receptor antagonist scopolamine hydrobromide (0.10 mg/kg) to investigate the possible involvement of ACh in naturally occurring spatial navigation in homing pigeons (Columba livia). Control pigeons receiving injections of saline or scopolamine methylbromide, an ACh antagonist that does not cross the blood-brain barrier, were oriented in a homeward direction when released from a location 8 km from home. In contrast, pigeons injected with scopolamine hydrobromide (0.10 mg/kg, i.m.) were less well oriented and took more time to return home from the same location. These results suggest that homing pigeon navigation is regulated, in part, by central cholinergic mechanisms.

Animals↗
PubMedDate not supplied

Effects of scopolamine and D-amphetamine on one-way, shuttle and inhibitory avoidance: a diallel analysis in mice.

The effects of scopolamine (2.0 mg/kg) and d-amphetamine (3.0 mg/kg) on one-way, shuttle and inhibitory avoidance performance were evaluated in 3 strains of mice (A/J, DBA/2J and C57BL/6J) and their 6 reciprocal F1 hybrids. In the saline condition, intermediate inheritance was observed in the inhibitory task, complete dominance for superior avoidance in the one-way task, and hybrid superiority in the shuttle situation. Administration of d-amphetamine disrupted inhibitory performance in all strains. In the shuttle task no amphetamine effect was observed in C57BL/6J mice, while improvement was seen in A/J and DBA/2J mice, as well as in all the hybrid corsses. No drug effect was seen in the one-way task. As with d-amphetamine, scopolamine disrupged performance in the inhibitory task among the inbreds, but had negligible effects in the hybrids. In the shuttle task, only the A/J mice exhibited improved performance, while a small decline in response rate was seen in one-way avoidance. Results were interpreted in terms of tha role of scopolamine and d-amphetamine in modifying non-associative factors involved in avoidance, and the interaction between associative and non-associative factors in modulating avoidance response rate.

Animals↗
PubMedDate not supplied

Effects of d-amphetamine and scopolamine on activity before and after shock in three mouse strains.

In three experiments the following results were obtained: (a) Activity was greater both prior to and following exposure to shock among C57BL/6J mice than in DBA/2J mice, which in turn was greater than that of A/J mice. (b) Scopolamine hydrobromide increased general activity in DBA/2 and A mice, but had either no effect or decreased activity in the C57BL/6 strain. Following exposure to shock, however, the disinhibitory effects of scopolamine were apparent in all three strains. (c) d-amphetamine increased activity in all three strains. Moreover, following the single shock d-amphetamine had excitatory effects among both A and DBA/2 mice such that activity exceeded the level observed with d-amphetamine alone. Following several shock presentations a small but significant excitation was observed in C57BL/6 mice as well. Data were interpreted in terms of disinhibitory and excitatory effects of scopolamine and d-amphetamine, respectively, as well as possible interactions between the catecholaminergic and cholinergic systems. In addition, implications for sources of strain differences in avoidance behavior are discussed.

Animals↗
PubMed1976

Role of stimulus locale on strain differences in active avoidance after scopolamine of D-amphetamine treatment.

Three strains of mice were trained in a shuttle avoidance task following treatment with scopolamine (2.0 mg/kg) or d-amphetamine (3.0 mg/kg). When required to run towards light (CS) to avoid shock, A/J mice acquired the response more readily than DBA/2J or C57BL/6J mice. However, when required to run away from the light, the strain differences were eliminated. Under both testing conditions scopolamine and d-amphetamine augmented the performance of A/J mice, but had no effect of even disrupted performance of C57BL/6J. In DBA/2J mice d-amphetamine augmented performance only in the toward condition. Results were interpreted to support the hypothesis that scopolamine and d-amphetamine improve performance by response-disinhibition and response excitation, respectively. The presence of associative difficulties limit the effects of these agents.

Animals↗
PubMed1980

The effects of scopolamine on three different types of suppressed behavior of rats.

Twelve albino rats were trained to lever press on a variable-interval one min schedule for sweetened condensed milk reinforcement. While responding on this schedule a two minute tone was presented. For one group it signalled a response contingent shock (Punishment), for another group it signalled the delivery of an unavoidable non-contingent shock at its termination (CER) and for a third group, reinforcement was withheld during the tone (Extinction). In the first experiment scopolamine in doses of 0.8 to 12.8 mg/kg did not alter response rates during the tone for any group. In a second experiment 16 hooded rats were tested with 6.4 mg/kg of scopolamine using a similar procedure, but with different shock levels, apparatus, reinforcement and session duration. For all three groups the drug depressed responding during the tone. It was concluded that when all other aspects of the situation are equated scopolamine will produce the same effect on behavior suppressed by punishment, CER and extinction.

Animals↗
PubMed1980

Effects of scopolamine, pentobarbital, and amphetamine on radial arm maze performance in the rat.

Rats were trained to obtain food pellets from the end of each arm of an eight-arm radial maze. Baseline performance was characterized by very few entries into arms from which the food pellet had already been obtained. In Experiment 1, neither d-amphetamine (0.1-3.0 mg/kg) nor pentobarbital (1.0-10.0 mg/kg) affected choice accuracy, although the rate of arm-entry increased after d-amphetamine and decreased after pentobarbital. Scopolamine (0.1-1.0 mg/kg), on the other hand, reduced both accuracy and the rate of arm entry. In a second experiment, the effects of scopoalmine were replicated using a between-subjects design. Methylscopolamine (0.17, 1.0 mg/kg) was found to have little effect on performance. Multiple response criteria were also compared in the second experiment. Scopolamine was found to affect runs farther out the arm differently than it affected abbreviated arm entrances. A post-trial feeding test was also included to evaluate changes in reinforcer effectiveness, and showed that food continued to be a reinforcer after both scopolamine and methylscopolamine.

Animals↗
PubMed1981

Interaction among d-amphetamine, scopolamine and genotype in avoidance behavior of rats.

Effects of d-amphetamine and scopolamine were investigated on either-way avoidance in two genetic lines. In the either-way task, the animal has the option to respond in either of the two directions available. Differences between the genetic lines were statistically significant under the effects of scopolamine, but were absent under the effects of d-amphetamine. It seems that scopolamine is more likely to disrupt responsiveness to visual stimuli in the low-avoidance line and this difference in responsiveness is influenced by bidirectional genetic selection.

Animals↗
PubMed1982

Scopolamine does not disrupt spatial working memory in rats.

The importance of cholinergic systems for spatial working memory was examined by injecting scopolamine at varying times during a 5 hr-long retention interval imposed between the rat's fourth and fifth choices in an 8 arm maze. Regardless of whether or not the testing procedure required the rats to adopt a spatial solution for the task, scopolamine (1.0-5.0 mg/kg) did not impair retention in a manner that was suggestive of an effect on working memory. Modest deficits observed in some conditions appeared to result from drug effects on performance. Previous findings of impaired acquisition of accurate spatial behavior by scopolamine-treated rats evidently reflect an influence of the drug on physiological systems other than those necessary to maintain working memory for spatial information.

Animals↗
PubMed1984

Effects of pre-training administration of scopolamine on learning and retention in the cockroach, P. americana.

The muscarinic cholinergic blocker, scopolamine, has no effect on acquisition or retention of the choice behavior of the cockroach, P. americana trained to turn right or left to avoid shock in a T-maze. Scopolamine does, however, prevent runway habituation during training, suggesting that such habituation may be dependent on central cholinergic synapses as there are no known peripheral cholinergic receptors in cockroaches. Previous work demonstrating that puromycin interferes with correct choice retention five hours after training taken together with our results demonstrating no effect of scopolamine on such retention, suggests that puromycin does not produce its amnesic effect on choice behavior by interferring with central cholinergic synaptic processes.

Animals↗
PubMed1985

Scopolamine degrades spatial working memory but spares spatial reference memory: dissimilarity of anticholinergic effect and restriction of distal visual cues.

The influence of the centrally active anticholinergic, scopolamine hydrobromide, on working and reference memory was studied in rats tested in a 12-arm radial maze. Both 0.25 and 0.5 mg/kg doses of the drug increased the number of working memory (WM) errors but had no effect on reference memory (RM) errors. A lower dose (0.125 mg/kg) was ineffective, as was the peripherally active anticholinergic, scopolamine methylbromide (0.5 mg/kg). Some of the behavioral effects of anticholinergics on spatial memory are mimicked by blindness or eliminating distal visual cues. If distal visual cues were more important for maintaining accurate WM than for RM, the selective effect of scopolamine on WM could be easily explained. But surrounding the maze with a curtain to eliminate extramaze cues increased RM errors without significantly increasing WM errors. Thus, the selective effect of anticholinergies on spatial memory in the radial maze is qualitatively different from the effect of restricting distal visual cues and must arise from some other action of the drug.

Animals↗