Conca Micó, Lluís

Universitat Autònoma de Barcelona. Facultat de Biociències

English

Diposit Digital de Documents de la UAB

The improvements on the depression symptoms last for more than 2 weeks. The persistence of the antidepressant eect on the body after sco-polamine’s clearance from plasma (elimination half-life = 2-4 hours) sug-gests that the mechanism is beyond the direct pharmacological action on muscarinic receptors.Learning and memory There are several papers which have analysed the eects of the scopolami-ne on learning and memory, as well there are dierent types of memory.Dierent studies demonstrate that blocking the muscarinic acetylcholine receptor by scopolamine can interfere in the encoding of new information and the short-term memory, but, in the other hand, has a small eect on re-trieval of information that was already stored.The object recognition memory in rats under the eects of the scopolami-ne is assessed in dierent papers. In these studies when the scopolamine was given before showing the sample, an impairment of the object recog-nition memory is found. Moreover, there is a study suggesting that scopo-lamine can improve the object recognition if the test is preformatted after the scopolamine injection. One possible reason for this !nding is that sco-polamine block the interference from other objects, because the scopola-mine block the acquisition of the memories of these objects.In a study in humans the capacity of learning word-pairs is assessed. The conclusions are that the scopolamine impair the encoding of new word paired associates. Moreover, in the study is shown that the scopolamine does not impair the retrieval of previously learned word pairs.Also in other study the e!ect of the scopolamine in working memory is shown, The working memory is the capacity that we have to hold in mind and mentally manipulate an information over a short period of time. In this study, a signi"cance disruption by scopolamine is observed. However, there are some studies that have questioned the fact that scopolamine can in#uence on the working memory. There are di!erent studies where the study of the scopolamine’s e!ect in anxiety-related memory has been assessed. And is found a relation be-tween the time of administration, if was before training or after, before trai-ning had more capacity to impar the anxiety-related memory.The modi"cation of the fear conditioning by scopolamine is also assessed in some studies. The reports in this area are quite variable, because there are reports which say that scopolamine impairs the context and cued fear conditioning. There are reports that says that scopolamine only impairs one, and there are reports which say that facilitates the fear cued conditio-ned.In addition the scopolamine can impaired the spatial cognitionAttention: Attention is a rich and complex psychological and neurobiological cons-truct. There is ample evidence for the involvement of acetylcholine in at-tentional modulation. Dierent experiments show that the increase on the acetylcholine lead to an increase of the attention. The scopolamine modu-les the concentration of acetylcholine, that’s why scopolamine aect in the attention. There have been dierent studies assessing this !eld, and the reports are dierent, in a study with humans the scopolamine impair the maintenance of attention. Also in a study with monkeys the accuracy was decreased. Furthermore in a study with rats performing 5-Choice Serial Reaction Time Task increase the number of omissions, but the animals which responded to the trial there was not any drug eect in the correct choice.AnxietyIt is hard to distinguish the eect of the scopolamine in the anxiety be-tween other eects that can have the scopolamine in the body (i.e. loco-motor activity). Nevertheless, in some experiments was found that scopo-lamine increase the anxiety-related behaviour.CONCLUSIONSSeen this summary of e!ects about the scopolamine, it can be con-cluded that the scopolamine may make a human loose the memory, because in the di!erent studies that are reviewed di!erent types of memory acquisition are impaired, this possible memory loose would be easier of the memories after the taken of scopolamine, because it’s shown that mostly impair the memories after the scopolamine was taken. One thing that it may be important is the dose. But, in order to be able to a$rm without doubt that the scopolamine make the humans loose their memory further studies with humans sub-jects will have to be done.About the e!ect of the scopolamine in the free will is hard to arrive to conclusions, because is it right that scopolamine may reduce the fear, and also can reduce the attention. Moreover, the people can get confused because a!ect the stimulus discrimination. Also the people can have less attention, can control less the motor activity, but from there arrive to the conclusion that scopolamine remove the free will is not possible. As before, further studies should be make in order to asses this possible e!ect. Moreover, some suppo-sed crimes related with scopolamine are committed in night clubs where the people normally is under the e!ect of other drugs (i.e. ethanol).BURUNDANGA : MYTH OR REALITY?Pharmacological analysis about the scopolamine   MOTIVESSCOPOLAMINE PROPIERTIES CHOLINERGIC HYPOTHESIS EFFECTSNON BEHAVIOURALSTIMULUS DISCRIMINATIONLOCOMOTOR ACTIVITYANTIDEPRESSANTLEARNING AND MEMORYATTENTIONANXIETYBIBLOGRAPHY: Figure 1: File:Datura stramonium 2 (2005 07 07).jpg [Internet]. Wikipedia, the free encyclopedia. [citat 31 maig 2015]. Recovered from: http://en.wikipedia.org/wiki/File:Datura_stramonium_2_(2005_07_07).jpgFigure 2: File:Scopolamine.svg [Internet]. Wikipedia, the free encyclopedia. [citat 31 maig 2015]. Recovered from: http://en.wikipedia.org/wiki/Scopolamine#/media/File:Scopolamine.svgFigure 3: File:Scopolamine_structure.png [Internet]. Wikipedia, the free encyclopedia. [citat 31 maig 2015]. Recovered from:http://en.wikipedia.org/wiki/Scopolamine#/media/File:Scopolamine_structure.pngKlinkenberg I, Blokland A. The validity of scopolamine as a pharmacological model for cognitive impairment: A review of animal behavioral studies. Neuroscience & Biobehavioral Reviews. juliol 2010;34(8):1307-50.Hodges DB, Lindner MD, Hogan JB, Jones KM, Markus EJ. Scopolamine induced de!cits in a battery of rat cognitive tests: comparisons of sensitivity and speci!city. Behavioural pharmacology. 2009;20(3):237-51. Lluís Conca Micó Biotechnolgoy DegreeUniversitat Autònoma de BarcelonaCONCLUSIONSMOTIVESThe reasons that drove me to write my Bachelor thesis about the sco-polamine, also known as Burundanga, were the dierent news and urban legends about this. The myths about this drug, a"rm that the Burundanga remove the free will and the memory of the people that take it. Other reason that made me declined for this theme was the importance that in my point of view the study of the drugs has to have. In our society is a fact that the people take drugs, and being re-alistic I think that can be a"rmed that the people will take drugs ever, so one of the best way to combat the drug abuse and the eect that can have in the society is to inform the people of the eects that the drugs can have, so in that way the people will be able to make a more accurate choice between taking or not taking drugs.SCOPOLAMINE PROPIERTESThe scopolamine is naturally found in dierent plants of Solanaceae family and other plants belonging to the same plant genera. These plants are naturally present around the world and are also used on gardening.Scopolamine is a muscarinic antagonist structurally similar to the neurotransmitter acetylcholine and acts by blocking the muscarinic acetylcholine receptors and is thus classi!ed as an anticholinergic.Anticholinergic agents, produce cognitive de!cits in humans, rats, and monkeys. The scopolamine have dierent in$uence in the orga-nisms. High doses of scopolamine have been shown to cause impair-ment in many cognitive tasks, and therefore interpreting the results is complex. Acetylcholine is widespread in the brain, and therefore scopolamine could potentially impact many dierent systems.MUSCARINIC RECEPTORS:There is a huge amount of studies that reveal the muscarinic acetyl-choline receptors play an important role regulating dierent func-tions of the central and peripheral nervous system.The muscarinic acetylcholine receptors belong to the super family of membrane-bound G-protein coupled receptors. There are !ve types (M1-M5) described and studied. These types are similar, in homology and identity in mouse, rat and human.The M1, M3, and M5 muscarinic acetylcholine receptors subtypes are positively coupled to the activation of phospholipase C, leading to the release of inositolphosphate second messengers. While M2 and M4 are associated with eector channels such as ion channels and adenyl cyclase.M1: Plays an important role in the memory and learning processes. Although, a knock out mice for this receptor show normal perfor-mance in cognition process, this may be due to the importance of this processes that some compensative processes may be develo-ped.M3: This receptor has an important role in the contraction of the smooth muscles, the pupil diameter and the salivation. Although that is widespread in all the brain no cognitive impairments have been found in knock out mice.M5: is mainly found in dierent peripheral and cerebral blood vesse-ls. A mice with this receptor knock out virtually lose the ability to dilate the cerebral arteries.M2 and M4: are important in the potassium-stimulated release of acetylcholine in hippocampal.M4: The autoinhibition of acetylcholine in striatum is mostly media-ted by this receptor.Figure 1:  Datura Stramonium Figure 2CHOLINERGIC HYPOTHESYSBEHAVIOURALCHOLINERGIC HYPOTHESIS The cholinergic hypothesis tries to explain the paper of acetylcholi-ne in learning and memory processes. A model has been proposed where acetylcholine is really important in the mode shifting be-tween encoding and retrieval in the hippocampus. With the propo-sed mechanism, information with high novelty content would induce dynamics in favour of learning the input, while similar to alre-ady stored patterns would induce a state that enhances retrieval of previous information.In this model, which is explained in the, conditions for acquisition of new information are high acetylcholine concentration, and low ace-tylcholine concentration allow to recall previous memories. That’s why encoding is impaired by low acetylcholine concentration and consolidation and retrieval would be aected by high acetylcholine concentration.Besides the cognition area, the acetylcholine is also related with the optimization of signal-to-noise ratio in the parietal and visual striate cortex, this characteristic is considered really important in the pro-cessing of the stimulus. In some experiments in this !elds was con-clude that the acetylcholine plays an important role in detection and processing of the relevant stimuli and suppression of the irrelevant ones.EFFECTS - NonbehaviouralThe non-behavioural eects of the scopolamine are mainly three, aects the pupil diameter, salivation and the function of the smooth muscle.The scopolamine dilates the pupil and impairs lens accommodation this eect is mainly mediated by the M3 muscarinic receptor. Also, the scopolamine can reduce salivation because the muscarinic re-ceptor M3 has an important role in the control of salivation, also the receptors M1 and M5 play a role. Other eect of scopolamine is the way that can in$uence on the function of the smooth muscle in the respiratory, vascular and gastrointestinal system. In these systems the smooth muscle is likely controlled by the M2 and M3 receptors.EFFECTS - BehaviouralStimulus discrimination: Pharmacological inactivation of muscarinic receptors by scopolami-ne frequently impairs performance on discrimination tasks. The ad-ministration of scopolamine, attenuated sound sequence discrimi-nation learning, $attened the response-gradient distribution in a temporal discrimination task and impaired visual discrimination (probably due to its peripheral eects on pupil diameter and lens ac-commodation).Stimulus discrimination is very sensitive to scopolamine treatment. However, it should be noted that not all studies have reported sco-polamine-induced discrimination de!cits, in favour of this idea is the !nding that scopolamine does not impair olfactory discrimination.Locomotor activity:The scopolamine in some studies increase the locomotor activity, this may be related to the lack of concentration, because the move-ments were spontaneous. In the other hand, there are other studies that reported decrease in motor activity.Antidepressant:There are studies that indicate that the muscarinic cholinergic recep-tor system is related with depression. The antidepressant eects me-diated by scopolamine were really fast, the patients said that they felt a relief within 24 h. In the other hand, no improvement was ob-served 150 minutes after scopolamine infusion.Figure 3

Burundanga: myth or reality? : pharmacological analysis about the scopolamine

https://ddd.uab.cat/pub/tfg/2015/141372/TFG_lluisconcamico.pdf

Burundanga: myth or reality? : pharmacological analysis about the scopolamine

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