Insect neurobiology: Oviposition crowd control.

A new study examines how Helicoverpa armigera females detect chemicals released by conspecific eggs in order to avoid laying more eggs on the same substrate. This work opens new avenues for basic research inquiries and offers a potential strategy for controlling insect pests.

Preclinical Models of Attention Deficit Hyperactivity Disorder: Neurobiology, Drug Discovery, and Beyond.

OBJECTIVE: We offer an overview of ADHD research using mouse models of nicotine exposure. METHOD: Nicotine exposure of C57BL/6 or Swiss Webster mice occurred during prenatal period only or during the prenatal and the pre-weaning periods. Behavioral, neuroanatomical and neurotransmitter assays were used to investigate neurobiological mechanisms of ADHD and discover candidate ADHD medications. RESULTS: Our studies show that norbinaltorphimine, a selective kappa opioid receptor antagonist is a candidate novel non-stimulant ADHD treatment and that a combination of methylphenidate and naltrexone has abuse deterrent potential with therapeutic benefits for ADHD. Other studies showed transgenerational transmission of ADHD-associated behavioral traits and demonstrated that interactions between untreated ADHD and repeated mild traumatic brain injury produced behavioral traits not associated with either condition alone. CONCLUSION: Preclinical models contribute to novel insights into ADHD neurobiology and are valuable tools for drug discovery and translation to benefit humans with ADHD.

Historical postmortem studies on catatonia: Close reading and analysis of Kahlbaum's cases and scientific texts between 1800 and 1900.

In the 19th century, postmortem brain examination played a central role in the search for the neurobiological origin of psychiatric and neurological disorders. During that time, psychiatrists, neurologists, and neuropathologists examined autopsied brains from catatonic patients and postulated that catatonia is an organic brain disease. In line with this development, human postmortem studies of the 19th century became increasingly important in the conception of catatonia and might be seen as precursors of modern neuroscience. In this report, we closely examined autopsy reports of eleven catatonia patients of Karl Ludwig Kahlbaum. Further, we performed a close reading and analysis of previously (systematically) identified historical German and English texts between 1800 and 1900 for autopsy reports of catatonia patients. Two main findings emerged: (i) Kahlbaum's most important finding in catatonia patients was the opacity of the arachnoid; (ii) historical human postmortem studies of catatonia patients postulated a number of neuroanatomical abnormalities such as cerebral enlargement or atrophy, anemia, inflammation, suppuration, serous effusion, or dropsy as well as alterations of brain blood vessels such as rupture, distension or ossification in the pathogenesis of catatonia. However, the exact localization has often been missing or inaccurate, probably due to the lack of standardized subdivision/nomenclature of the respective brain areas. Nevertheless, Kahlbaum's 11 autopsy reports and the identified neuropathological studies between 1800 and 1900 made important discoveries, which still have the potential to inform and bolster modern neuroscientific research in catatonia.

Polyphenols in Inner Ear Neurobiology, Health and Disease: From Bench to Clinics.

There is substantial experimental and clinical interest in providing effective ways to both prevent and slow the onset of hearing loss. Auditory hair cells, which occur along the basilar membrane of the cochlea, often lose functionality due to age-related biological alterations, as well as from exposure to high decibel sounds affecting a diminished/damaged auditory sensitivity. Hearing loss is also seen to take place due to neuronal degeneration before or following hair cell destruction/loss. A strategy is necessary to protect hair cells and XIII cranial/auditory nerve cells prior to injury and throughout aging. Within this context, it was proposed that cochlea neural stem cells may be protected from such aging and environmental/noise insults via the ingestion of protective dietary supplements. Of particular importance is that these studies typically display a hormetic-like biphasic dose-response pattern that prevents the occurrence of auditory cell damage induced by various model chemical toxins, such as cisplatin. Likewise, the hormetic dose-response also enhances the occurrence of cochlear neural cell viability, proliferation, and differentiation. These findings are particularly important since they confirmed a strong dose dependency of the significant beneficial effects (which is biphasic), whilst having a low-dose beneficial response, whereas extensive exposures may become ineffective and/or potentially harmful. According to hormesis, phytochemicals including polyphenols exhibit biphasic dose-response effects activating low-dose antioxidant signaling pathways, resulting in the upregulation of vitagenes, a group of genes involved in preserving cellular homeostasis during stressful conditions. Modulation of the vitagene network through polyphenols increases cellular resilience mechanisms, thus impacting neurological disorder pathophysiology. Here, we aimed to explore polyphenols targeting the NF-E2-related factor 2 (Nrf2) pathway to neuroprotective and therapeutic strategies that can potentially reduce oxidative stress and inflammation, thus preventing auditory hair cell and XIII cranial/auditory nerve cell degeneration. Furthermore, we explored techniques to enhance their bioavailability and efficacy.

Requerimientos para la producción e implementación de un Material Educativo Digital / Requirements for Producing and Implementing Digital Educational Materials

Introducción: La revolución digital ha llegado al campo educativo y exige que los entornos educativos digitales generen experiencias educativas contundentes. Para realizar este proceso, es fundamental diseñar y construir un material educativo digital (MED) ajustado a los lineamientos tecnológicos, técnicos y pedagógicos enmarcados en la neurobiología del aprendizaje (NA) del estudiante. Objetivo: Evaluar los elementos necesarios para la producción de un material educativo digital (MED) inédito, mediante su implementación en estudiantes. Métodos: Se realizó un análisis cuantitativo a través del Test de Wilcoxon SR con el software SPSS de IBM, y un análisis cualitativo con el software QDA Miner. Posteriormente, se triangularon los datos. Resultados: En el análisis cuantitativo se obtuvo una diferencia estadísticamente significativa entre el pretest y el postest (p < 0,001) y la mediana entre dicha diferencia de 22,6 por ciento. En el análisis cualitativo se definieron tres categorías: los comentarios positivos de la experiencia, las sugerencias de los estudiantes al proceso y las dificultades técnicas surgidas durante la implementación. Conclusiones: Son evidentes el interés, la motivación, el enganche y el disfrute de los estudiantes de una forma activa en el proceso de aprendizaje, que proporcionan un punto de partida para transformar las prácticas educativas con resultados significativos(AU)

Introduction: The digital revolution has reached the educational field and demands that digital educational environments generate powerful educational experiences. To carry out this process, it is essential to design and build a digital educational material adjusted to the technological, technical and pedagogical guidelines framed in the student's neurobiology of learning. Objective: To evaluate the necessary elements for the production of an unpublished digital educational material, through its implementation in students. Methods: A quantitative analysis was performed through the Wilcoxon SR test using the IBM SPSS software, together with a qualitative analysis using the QDA Miner software. Subsequently, the data were triangulated. Results: The quantitative analysis yielded a statistically significant difference between pretest and posttest (p < 0.001), as well as a median difference of 22.6 percent. The qualitative analysis permitted to define three categories: positive comments on the experience, the students' suggestions to the process, and technical difficulties encountered during the implementation. Conclusions: The students' active interest in, motivation for, engagement towards and enjoyment of the learning process are evident, facts that provide a starting point for transforming educational practices with significant outcomes(AU)

Christofredo Jakob, los cimientos de la neurociencia argentina / Christofredo Jakob, the foundations of argentine neuroscience

El presente artículo es una reseña biográfica de la vida del Dr. Christofredo Jakob, desde su formación en Alemania, las personalidades que acompañaron su desarrollo y las publicaciones científicas en suelo germano. Luego llegarían los inicios de su trabajo en la Argentina y los principales alcances de sus investigaciones. A través de esta reseña recorremos los comienzos del estudio sistemático del sistema nervioso en el país y recordamos el Día del Neurocientífico argentino. (AU)

This article is a biographical review of the life of Dr. Christofredo Jakob, from his training in Germany, the personalities who accompanied his development and the scientific publications on German soil. Then came the beginnings of his work in Argentina and the main achievements of his research. Through this review, we retrace the beginnings of the systematic study of the nervous system in the country and we remember the Day of the Argentine Neuroscientist. (AU)

Effect of chronic unpredictable stress in female Wistar-Kyoto rats subjected to progesterone withdrawal: Relevance for Premenstrual Dysphoric Disorder neurobiology.

Premenstrual Dysphoric Disorder (PMDD) is related to an abrupt drop in progesterone and impairments in the HPA axis that cause anxiety. Suffering persons report higher daily-life stress and anxiety proneness that may contribute to developing PMDD, considered a chronic stress-related disorder. Here, we explored the effect of chronic unpredictable stress (CUS) in rats subjected to progesterone withdrawal (PW) and evaluated gene expression of HPA axis activation in the stress-vulnerable Wistar-Kyoto (WKY) rat strain that is prone to anxiety. Ovariectomized WKY rats were randomly assigned to CUS or Standard-housed conditions (SHC) for 30 days. To induce PW, animals received 2 mg/kg of progesterone on day 25th for 5 days; 24 h later, they were tested using the anxiety-like burying behavior test (BBT). After behavioral completion, rats were euthanized, and brains were extracted to measure Crh (PVN) and Nr3c1 (hippocampus) mRNA. Blood corticosterone and vasopressin levels were determined. Results showed that PW exacerbated anxiety-like behaviors through passive coping in CUS-WKY. PW decreased Crh-PVN mRNA and the Nr3c1-hippocampal mRNA expression in SHC. CUS decreased Crh-PVN mRNA compared to SHC, and no further changes were observed by PW or BBT exposure. CUS reduced Nr3c1-hippocampal gene expression compared to SHC animals, and lower Nr3c1 mRNA was detected due to BBT. The PW increased corticosterone in SHC and CUS rats; however, CUS blunted corticosterone when combined with PW+BBT and similarly occurred in vasopressin concentrations. Chronic stress blunts the response of components of the HPA axis regulation when PW and BBT (systemic and psychogenic stressors, respectively) are presented. This response may facilitate less adaptive behaviors through passive coping in stress-vulnerable subjects in a preclinical model of premenstrual anxiety.

The NDR/LATS protein kinases in neurobiology: Key regulators of cell proliferation, differentiation and migration in the ocular and central nervous system.

Nuclear Dbf2-related (NDR) kinases are a subgroup of evolutionarily conserved AGC protein kinases that regulate various aspects of cell growth and morphogenesis. There are 4 NDR protein kinases in mammals, LATS1, LATS2 and STTK8/NDR1, STK38L/NDR2 protein kinases. LATS1 and 2 are core components of the well-studied Hippo pathway, which play a critical role in the regulation of cell proliferation, differentiation, and cell migration via YAP/TAZ transcription factor. The Hippo pathways play an important role in nervous tissue development and homeostasis, especially with regard to the central nervous system (CNS) and the ocular system. The ocular system is a very complex system generated by the interaction in a very tightly coordinated manner of numerous and diverse developing tissues, such as, but not limited to choroidal and retinal blood vessels, the retinal pigmented epithelium and the retina, a highly polarized neuronal tissue. The retina development and maintenance require precise and coordinated regulation of cell proliferation, cell death, migration, morphogenesis, synaptic connectivity, and balanced homeostasis. This review highlights the emerging roles of NDR1 and NDR2 kinases in the regulation of retinal/neuronal function and homeostasis via a noncanonical branch of the Hippo pathway. We highlight a potential role of NDR1 and NDR2 kinases in regulating neuronal inflammation and as potential therapeutic targets for the treatment of neuronal diseases.

Molecular and Cellular Neurobiology of Circadian and Circannual Rhythms in Migraine: A Narrative Review.

Migraine-a primary headache-has circadian and circannual rhythms in the onset of attacks. The circadian and circannual rhythms involve the hypothalamus, which is strongly associated with pain processing in migraines. Moreover, the role of melatonin in circadian rhythms has been implied in the pathophysiology of migraines. However, the prophylactic effect of melatonin in migraines is controversial. Calcitonin gene-related peptide (CGRP) has recently attracted attention in the pathophysiology and treatment of migraines. Pituitary adenylate cyclase-activating peptide (PACAP)-a neuropeptide identical to CGRP-is a potential therapeutic target after CGRP. PACAP is involved in the regulation of circadian entrainment to light. This review provides an overview of circadian and circannual rhythms in the hypothalamus and describes the relationship between migraines and the molecular and cellular neurobiology of circadian and circannual rhythms. Furthermore, the potential clinical applications of PACAP are presented.

Chemical Flavorants in Vaping Products Alter Neurobiology in a Sex-Dependent Manner to Promote Vaping-Related Behaviors.

Electronic nicotine delivery systems (ENDS) are distinctly different from combustible cigarettes because of the availability of flavor options. Subjective measures have been used to demonstrate that adults and adolescents prefer flavors for various reasons; (1) they are pleasing and (2) they mask the harshness of nicotine. Despite this, there have been few investigations into the molecular interactions that connect chemical flavorants to smoking or vaping-related behaviors. Here, we investigated the effects of three chemical flavorants (hexyl acetate, ethyl acetate, and methylbutyl acetate) that are found in green apple (GA) ENDS e-liquids but are also found in other flavor categories. We used a translationally relevant vapor self-administration mouse model and observed that adult male and female mice self-administered GA flavorants in the absence of nicotine. Using α4-mCherryα6-GFP nicotinic acetylcholine receptor (nAChR) mice, we observed that mice exposed to GA flavorants exhibited a sex-specific increase (upregulation) of nAChRs that was also brain-region specific. Electrophysiology revealed that mice exposed to GA flavorants exhibited enhanced firing of ventral tegmental area dopamine neurons. Fast-scan cyclic voltammetry revealed that electrically stimulated dopamine release in the nucleus accumbens core is increased in mice that are exposed to GA flavorants. These effects were similarly observed in the medial habenula. Overall, these findings demonstrate that ENDS flavors alone change neurobiology and may promote vaping-dependent behaviors in the absence of nicotine. Furthermore, the flavorant-induced changes in neurobiology parallel those caused by nicotine, which highlights the fact that nonmenthol flavorants may contribute to or enhance nicotine reward and reinforcement.SIGNIFICANCE STATEMENT The impact of flavors on vaping is a hotly debated topic; however, few investigations have examined this in a model that is relevant to vaping. Although a full understanding of the exact mechanism remains undetermined, our observations reveal that chemical flavorants in the absence of nicotine alter brain circuits relevant to vaping-related behavior. The fact that the flavorants investigated here exist in multiple flavor categories of vaping products highlights the fact that a multitude of flavored vaping products may pose a risk toward vaping-dependent behaviors even without the impact of nicotine. Furthermore, as the neurobiological changes have an impact on neurons of the reward system, there exists the possibility that nonmenthol flavorants may enhance nicotine reward and reinforcement.

Integrative brain structural and molecular analyses of interaction between tobacco use disorder and overweight among male adults.

Tobacco smoking and overweight lead to adverse health effects, which remain an important public health problem worldwide. Researches indicate overlapping pathophysiology may contribute to tobacco use disorder (TUD) and overweight, but the neurobiological interaction mechanism between the two factors is still unclear. This study used a mixed sample design, including the following four groups: (i) overweight long-term smokers (n = 24, age = 31.80 ± 5.70, cigarettes/day = 20.50 ± 7.89); (ii) normal weight smokers (n = 28, age = 31.29 ± 5.56, cigarettes/day = 16.11 ± 8.35); (iii) overweight nonsmokers (n = 19, age = 33.05 ± 5.60), and (iv) normal weight nonsmokers (n = 28, age = 31.68 ± 6.57), a total of 99 male subjects. All subjects underwent T1-weighted high-resolution MRI. We used voxel-based morphometry to compare gray matter volume (GMV) among the four groups. Then, JuSpace toolbox was used for cross-modal correlations of MRI-based modalities with nuclear imaging derived estimates, to examine specific neurotransmitter system changes underlying the two factors. Our results illustrate a significant antagonistic interaction between TUD and weight status in left dorsolateral prefrontal cortex (DLPFC), and a quadratic effect of BMI on DLPFC GMV. For main effect of TUD, long-term smokers were associated with greater GMV in bilateral OFC compared with nonsmokers irrespective of weight status, and such alteration is negatively associated with pack-year and FTND scores. Furthermore, we also found GMV changes related to TUD and overweight are associated with µ-opioid receptor system and TUD-related GMV alterations are associated with noradrenaline transporter maps. This study sheds light on novel multimodal neuromechanistic about the relationship between TUD and overweight, which possibly provides hints into future treatment for the special population of comorbid TUD and overweight.

Adolescent development: From neurobiology to psychopathology.

Adolescence is a time of major psychological development in the cognitive, affective, and social domains. Development in these domains can also show interactions with each other. One way in which these interactions between these domains become apparent is in the form of risk-taking behavior in adolescence. Compared to children and adults, adolescents show increased risky decision-making. An example of risk-taking behavior is substance use, including smoking and the use of e-cigarettes (Huizink). A leading explanation for risk-taking behavior has been an increase in reward sensitivity in adolescence. However, adolescents also show differential processing of risk compared to children and adults. A focus on risk processing could broaden the perspective on adolescent risk-taking behavior (van Duijvenvoorde).

Neurobiology, Stem Cell Biology, and Immunology: An Emerging Triad for Understanding Tissue Homeostasis and Repair.

The peripheral nervous system (PNS) endows animals with the remarkable ability to sense and respond to a dynamic world. Emerging evidence shows the PNS also participates in tissue homeostasis and repair by integrating local changes with organismal and environmental changes. Here, we provide an in-depth summary of findings delineating the diverse roles of peripheral nerves in modulating stem cell behaviors and immune responses under steady-state conditions and in response to injury and duress, with a specific focus on the skin and the hematopoietic system. These examples showcase how elucidating neuro-stem cell and neuro-immune cell interactions provides a conceptual framework that connects tissue biology and local immunity with systemic bodily changes to meet varying demands. They also demonstrate how changes in these interactions can manifest in stress, aging, cancer, and inflammation, as well as how these findings can be harnessed to guide the development of new therapeutics.

Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics.

Schizophrenia has been conceptualized as a neurodevelopmental disorder with synaptic alterations and aberrant cortical-subcortical connections. Antipsychotics are the mainstay of schizophrenia treatment and nearly all share the common feature of dopamine D2 receptor occupancy, whereas glutamatergic abnormalities are not targeted by the presently available therapies. D-amino acids, acting as N-methyl-D-aspartate receptor (NMDAR) modulators, have emerged in the last few years as a potential augmentation strategy in those cases of schizophrenia that do not respond well to antipsychotics, a condition defined as treatment-resistant schizophrenia (TRS), affecting almost 30-40% of patients, and characterized by serious cognitive deficits and functional impairment. In the present systematic review, we address with a direct and reverse translational perspective the efficacy of D-amino acids, including D-serine, D-aspartate, and D-alanine, in poor responders. The impact of these molecules on the synaptic architecture is also considered in the light of dendritic spine changes reported in schizophrenia and antipsychotics' effect on postsynaptic density proteins. Moreover, we describe compounds targeting D-amino acid oxidase and D-aspartate oxidase enzymes. Finally, other drugs acting at NMDAR and proxy of D-amino acids function, such as D-cycloserine, sarcosine, and glycine, are considered in the light of the clinical burden of TRS, together with other emerging molecules.

Neurobiology and Symptomatology of Post-Acute Alcohol Withdrawal: A Mixed-Studies Systematic Review.

OBJECTIVE: This study aims to review the neurobiology and symptomatology of post-acute alcohol withdrawal syndrome (PAWS). METHOD: We conducted a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-guided systematic review of articles from two databases for English-language randomized and nonrandomized studies involving PAWS published between database inception and December 2020. RESULTS: Twenty-seven studies met inclusion criteria. PAWS involves predominantly negative affect, which develops in early abstinence and can persist for 4-6 months or longer. Symptoms include anxiety, dysphoria, anhedonia, sleep disturbance, cognitive impairment, cravings, and irritability. PAWS symptoms appear to be risk factors for recurrent alcohol consumption. They have been associated with reported neurobiological differences in evoked potentials; measures of orexins, cortisol, serotonin, and pancreatic polypeptides; and neuroadaptation changes in the nucleus accumbens and the prefrontal cortex. CONCLUSIONS: There is credible evidence to support the concept of PAWS based on this review's findings. There remains a need to develop and test specific criteria for PAWS. High-quality treatment studies involving agents addressing its neurobiological underpinnings are also recommended.

Wearable OPM-MEG: A changing landscape for epilepsy.

Magnetoencephalography with optically pumped magnometers (OPM-MEG) is an emerging and novel, cost-effective wearable system that can simultaneously record neuronal activity with high temporal resolution ("when" neuronal activity occurs) and spatial resolution ("where" neuronal activity occurs). This paper will first outline recent methodological advances in OPM-MEG compared to conventional superconducting quantum interference device (SQUID)-MEG before discussing how OPM-MEG can become a valuable and noninvasive clinical support tool in epilepsy surgery evaluation. Although OPM-MEG and SQUID-MEG share similar data features, OPM-MEG is a wearable design that fits children and adults, and it is also robust to head motion within a magnetically shielded room. This means that OPM-MEG can potentially extend the application of MEG into the neurobiology of severe childhood epilepsies with intellectual disabilities (e.g., epileptic encephalopathies) without sedation. It is worth noting that most OPM-MEG sensors are heated, which may become an issue with large OPM sensor arrays (OPM-MEG currently has fewer sensors than SQUID-MEG). Future implementation of triaxial sensors may alleviate the need for large OPM sensor arrays. OPM-MEG designs allowing both awake and sleep recording are essential for potential long-term epilepsy monitoring.

Dificultades interpersonales en los trastornos alimentarios: un modelo psiconeurobiológico explicativo/comprensivo / Interpersonal difficulties in eating disorders: an explanatory/ comprehensive psychoneurobiological model

RESUMEN: Antecedentes: Los trastornos alimentarios (TCA) presentan entre sus síntomas disfunciones psicosociales como ansiedad social, alexitimia y falta de asertividad. Objetivo: Se propone un modelo explicativo/comprensivo que integra aspectos de psiconeurobiología y comportamiento útil para la clínica. Método: Se evaluó una revisión de la literatura en Medline / PubMed, SciELO y bases de datos de textos especializados con criterios de calidad. Fueron seleccionados conceptos centrales para construir una coherencia que permitiera la lectura psiconeurobiológica del fenómeno y su aplicación clínica. Resultados: Cuatro factores fueron dispuestos a significar: 1- sistema de alarma; 2- sistema de recompensa 3- cerebro social; 4-mecanismos de control (inhibición/excitación). Se dispusieron mostrando la complejidad de su interacción psicofisiológica. Se sugiere que la ingesta de alimentos podría funcionar como una forma primaria de equilibrio cuando hay fallas en alguno de los sistemas expuestos. Conclusión: Se presenta un modelo de integración psiconeurobiológico útil para explicar la dificultad interpersonal en TCA. Esta forma de comprensión facilita: la conexión entre las investigaciones emergentes en TCA y DI; la toma de decisiones clínicas y orientan el pronóstico y las alternativas de tratamiento.

ABSTRACT Background: Eating disorders (ED) are characterized by psychosocial disfunctions, like social anxiety, alexithymia and lack of assertiveness. Objective: To propose a comprehensive integrative model including neurobiology and behavior aspects. Method: A literature review on Medline/PubMed, SciELO and specialized texts databases were assessed against quality criteria. Core concepts were extracted and coherence articulated. Results: Four factors were disposed to meaning: alarm and reward system with social brain and control (inhibition/excitation) mechanisms. They were articulate in a complex psychophysiological interplay. They were associated with social behaviours achieved/not achieved during development. Food intake could operate like a pathological balance to psychopathological effects Conclusion: An explanatory/comprehensive psychoneurobiological model to understand social function in ED is proposed. This form of understanding facilitates: the connection between emerging research in eating disorders and ID; clinical decision-making and guide the prognosis and treatment alternatives.

Dependencia de sustancias psicoactivas en Costa Rica: aspectos epidemiológicos y neurobiológicos de una enfermedad incomprendida / Substance dependence in Costa Rica: epidemiological and neurobiological aspects of a misunderstood disease

Resumen Introducción: se estima que entre un 80 % y un 90 % de la población mundial ha consumido sustancias psicoactivas (SPA), pero solo un 15 % llega a desarrollar una dependencia. El objetivo de este ensayo es describir los antecedentes epidemiológicos, los aspectos clínicos y los mecanismos neurobiológicos asociados a la dependencia de SPA. Luego, se reflexiona sobre algunas estrategias ambientales para su prevención y/o tratamiento. Proposición: la dependencia no es un simple vicio producto de la holgazanería o la falta de carácter, sino, un trastorno neuropsquiátrico que debe ser reconocido como tal. Para ello, es indispensable conocer sus factores etiológicos, así como los mecanismos neurobiológicos involucrados. Argumentos para la discusión: todas las SPA activan directa o indirectamente el sistema dopaminérgico mesolímbico, el cual, tras el abuso, produce la sensibilización del sistema motivacional y la desensibilización del sistema hedónico. Este fenómeno provoca el uso más frecuente y en mayor cantidad, a pesar de que los efectos placenteros sean cada vez menores. El malestar físico y emocional causado por el síndrome de abstinencia contribuye a dicha compulsión, la cual se sale de control producto de las alteraciones del funcionamiento ejecutivo y la corteza prefrontal. Conclusiones: la dependencia es una enfermedad del cerebro inducida por el consumo crónico de las SPA en conjunto con factores neurobiológicos y psicosociales de vulnerabilidad. El acceso a contacto social, ejercicio físico y estimulación sensorio-cognitiva podría representar una estrategia altamente eficaz para el manejo de la dependencia y el mejoramiento de la salud mental.

Abstract Introduction: It has been estimated that 80% to 90% of the population worldwide has ever consumed psychoactive substances (PAS), but only 15% will develop addiction. The goal of the current essay is to describe concisely the epidemiological background, the clinical foundations, and neurobiological mechanisms of addiction. Finally, it will briefly examine some environmental strategies aimed to prevent and/or treat addiction. Addiction is not a simple vice consequence of laziness or lack of character, but a neuropsychiatric disorder that must be recognized as such. Proposal: To attain this ultimate goal, the etiological factors and the neurobiological mechanisms of addiction must be revealed and disseminated. Arguments for discussion: All PAS directly or indirectly activate the mesolimbic dopaminergic system, which -after repeated intake- sensitizes and desensitizes the motivational and the hedonic system, respectively. This phenomenon causes PAS to be consumed more frequently and at higher doses despite their effects being progressively less rewarding. Consequently, the physical and emotional distress derived from the withdrawal syndrome exacerbates the compulsive PAS intake, while the completely loss of control results from impairments in the executive functions and the prefrontal cortex. Conclusions: Addiction is a brain disease induced by the chronic consumption of PAS combined with neurobiological and psychosocial risk factors. Exposure social contact, physical exercise, and sensory-cognitive stimulation may constitute a highly effective strategy for preventing and treating addiction and improving mental health as well.