El cerebro y las drogas, sus mecanismos neurobiológicos

SUMMARYThe pleasant sensation experienced when, for example eating orhaving sex is regulated by the motivation-rewarding system. Thisrewarding sensation makes the subject to repeat the behavior in orderto obtain the reinforcer once more. This system can be corrupted bydrugs of abuse by triggering an «intense feeling of pleasure» andinducing plastic changes. In normal conditions, a natural reinforceris a stimulus generating a benefit to the organism. For example,food will provide energy and structure among many other benefits.Sex, in turn, accomplishes the function of giving new beings to thespecies and to create boundaries between subjects to generate groupsand culture. Due to these facts, it is crucial to reinforce this kind ofbehaviors. They are crucial for the subject’s life. In contrast, drugs donot produce any benefit to the subject or group. Although in ancienttimes human beings used drugs as a means to develop and practicetheir mysticism, such practice is no longer associated with the use ofdrugs. With the exception of present time aboriginal communities,none of the regular users in our countries consume drugs with ritual-mystical purposes. Hence, we have to accept that drugs are of nouse for human beings. They do not help us as species to have moreadapted, intelligent or developed subjects in our communities.However, their ability to stimulate the rewarding system makes thempopular and dangerous to the individual’s health and life.The motivation-rewarding system is regulated by numerousneurotransmitters, among them dopamine, that is released in thenucleus accumbens (NAc) and synthesized by the neurons located inthe ventral tegmetal area (VTA). There are other substances thatmodulate the activity of the dopaminergic neurons in the VTA, suchas serotonin, acetylcholine, gamma-aminobutyric acid (GABA) andglutamate. The activation of the VTA and its consequent activation ofthe NAc enhance the release of neuromodulators such as endorphinsand endocannabinoids, thus generating the subjective sensation ofpleasure. All these interactions trigger the activity of memory systemsgenerating a memory trace encoding the characteristics of thesubstance or behavior causing pleasure. This occurs in the contextthat the brain accepts these substances or behaviors as beneficial tothe organism.The punishment system is also a very important system workingin tight communication with the pleasure system. Fear is one of themost critical adapting behaviors for any subject in the animalkingdom. Fear helps us to avoid dangerous stimulus and behaviors.There is also pleasure involved in escaping this kind of situations. Itseems like there is an interaction between the motivation-rewardingand the punishment systems. As a result, there is a balance at timesin favor of pleasure, at times in favor of punishment depending onthe quality of the stimulus. This balance gives the valence to theemotion triggered by the stimulus. A stimulus with a positive valencewill increase the probability of exhibiting the behavior displayed toobtain it, while a stimulus with a negative valence will increase theprobability of exhibiting the behavior displayed to avoid it.In this context, the so-called non-natural reinforcers such asdrugs of abuse act directly on the pleasure system. For example,nicotine acts on the nicotinic receptor of ACh, alcohol, on the receptorof GABAa and glutamate (NMDA), marihuana on theendocannabinoid receptor (CB1R), located in the motivation-rewarding system triggering an «intense sensation of pleasure». However, two main shortcomings make drugs of abuse dangerous:first, their effect is short and, second, they do not convey any beneficialeffect to the organism whatsoever. Brain mechanisms not very welldefined detect this lack of benefit; hence, the motivation-rewardingsystem reduces its response by means of at least two plastic changes,reducing the availability of receptors (epigenetic changes induced bythe drug) and by increasing the activity of the punishment system tomaintain the balance. As a result, the subject does not experiencethe same pleasure with the same dose of the drug. In the clinic wecall this phenomenon tolerance. If the individual insists in pursuingthe same intensity of pleasure, he/she has to consume more of thedrug, forcing the brain to strengthen its plastic changes. In this context,we can say that these systems are defending themselves against theaction of the drug. Then, why do subjects insist in pursuing the effectof drugs? Very likely because the substrate of the subject’s disorderresides anywhere in the brain but in the pleasure system. If so, thisindicates that drug addiction is a disorder caused by another disease,very likely a psychiatric one.Several factors contribute to generate drug addiction, i. e. social,psychological and genetic. Genes contribute in different ways togenerate the subject’s vulnerability to suffer an addiction. A genemutation (alteration in genetic information) or a given polymorphism(the existence of multiple alleles of a gene in a population) canproduce a dysfunctional protein or alter its normal levels. Suchchanges may make some individuals vulnerable to the initial use ofdrugs of abuse. However, those genes facilitating adjustments in themotivation-rewarding system that occur after the repeatedActualizacion por temas