A propósito de la oposición formal/material: cuatro aproximaciones interdisciplinares sobre un mismo tema = On the formal/substantive opposition: four interdisciplinary approaches on the same subject

 Resumen : El pensamiento cientifista moderno que pretende obtener certezas mediante la búsqueda de afirmaciones indiscutibles sobre hechos irrefutables derivados de la protocolización y estandarización de procedimientos que nos alejen del debate sobre los valores e intereses particulares, ha olvidado que la formalización que requiere el diseño de todo procedimiento aplicable a casos concretos supone siempre la incorporación de finalidades relativas a valores e intereses. Este olvido, propio del pensamiento moderno, se ha visto acompañado de otra actitud: la hiperespecialización de las disciplinas, de manera que sus consecuencias y los debates sobre las mismas en una especie de constante reinvención de la rueda se han reproducido estérilmente. Mediante un estudio interdisciplinar que pone de manifiesto las líneas comunes en debates paradigmáticos en los campos del derecho, la retórica, la lingüística, la ciencia cognitiva y la inteligencia artificial simbólica, así como la teoría política, pretendemos poner de manifiesto la incapacidad de las teorías procesualistas de satisfacer esa aspiración de certeza y neutralidad absoluta propia de las sociedades postmetafísicas en sentido habermasiano.Palabras clave: Debido proceso, debido proceso sustantivo, inteligencia artificial simbólica, filosofía política, J.Rawls, J. Habermas, C. Mouffe. Abstract :The modern scientificist thought that seeks to obtain certainty through the search for indisputable statements about irrefutable facts derived from the protocolization and standardization of procedures that take us away from the debate on particular values and interests, has forgotten that the formalization required for the design of any procedure applicable to specific cases always involves the addition of purposes related to values and interests. This oversight, typical of modern thought, has been accompanied by another attitude: the hyperspecialization of the disciplines, so that its consequences and the debates about them in a kind of constant reinvention of the wheel have been reproduced sterilely. Through an interdisciplinary study that highlights the common lines in paradigmatic debates in the fields of law, rhetoric, linguistics, cognitive science and symbolic artificial intelligence, as well as political theory, we intend to emphasize the inability of processual theories to satisfy an aspiration of absolute neutrality typical of postmetaphysical societies in the Habermasian sense. Keywords: Due process, substantive due process, symbolic artificial intelligence, political philosophy, J. Rawls, J. Habermas, C. Mouffe

Constituciones inconstitucionales, soberanos limitados. Presentificación y procedimentalidad sustantiva.

Se trata de una indagación acerca de los límites del poder soberano que busca identificar el fundamento de la autoridad, conforme al respectivo modo de fundamentación, identificando los criterios racionales del fundamento moderno como criterio que nos permita señalar cuándo en las manifestaciones del poder legítimo no se verifique la necesaria coherencia interna -que denominaremos técnicamente consistencia pragmática-. No pretendemos por tanto elaborar un sistema que identifique universalmente lo legítimo, sino que identifique lo inconsistente -es decir, lo autorrefutativo- dentro de un determinado sistema de legitimidad. Sus conclusiones: (1) los valores constituyen indicadores que nos informan de la consistencia pragmática de los sistemas políticos; (2) que de esta necesidad de consistencia se deduce que toda democracia es militante; y (3) si la ley es la típica expresión de la voluntad popular en democracia, esta voluntad se traduce siempre mediante fórmulas jurídicas: es decir, desarrollar un círculo virtuoso en el que la vida vivida dentro los límites que propicia un relato determinado -fundamento estructuralmente posibilitante de la propia vida- no pueda desarrollarse sustancialmente como la refutación de ese relato

Dopamine D4 receptor counteracts morphine-induced changes in M opioid receptor signaling in the striosomes of the rat caudate putamen.

Morphine is one of the most potent analgesic drugs used to relieve moderate to severe pain. After long-term use of morphine, neuroadaptive changes in the brain promotes tolerance, which result in a reduced sensitivity to most of its effects with attenuation of analgesic efficacy, and dependence, revealed by drug craving and physical or psychological manifestations of drug withdrawal. The mu opioid receptor (MOR) is critical, not only in mediating morphine analgesia, but also in addictive behaviors by the induction of a strong rewarding effect. We have previously shown that dopamine D4 receptor (D4R) stimulation counteracts morphine-induced activation of dopaminergic nigrostriatal pathway and accumulation of Fos family transcription factors in the caudate putamen (CPu). In the present work, we have studied the effect of D4R activation on MOR changes induced by morphine in the rat CPu on a continuous drug treatment paradigm, by analyzing MOR protein level, pharmacological profile, and functional coupling to G proteins. Furthermore, using conditioned place preference and withdrawal syndrome test, we have investigated the role of D4R activation on morphine-related behavioural effects. MOR immunoreactivity, agonist binding density and its coupling to G proteins are up-regulated in the striosomes by continuous morphine treatment. Interestingly, co-treatment of morphine with the dopamine D4 receptor (D4R) agonist PD168,077 fully counteracts these adaptive changes in MOR, in spite of the fact that continuous PD168,077 treatment increases the [3H]DAMGO Bmax values to the same degree as seen after continuous morphine treatment. In addition, the administration of the D4R agonist counteracts the rewarding effects of morphine, as well as the development of physical dependence. The present results give support for the existence of antagonistic functional D4R-MOR receptor-receptor interactions in the adaptive changes occurring in MOR of striosomes on continuous administration of morphine and preventing morphine-related behaviour.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Dopamine D4 receptor activation counteracts nigrostriatal pathway activation by morphine: relevance in drug addiction.

Morphine induces dopamine release in the caudate putamen (CPu), which promotes stereotyped behavior and habit learning for drug-seeking and –taking. Nigrostriatal pathway stimulation by morphine is due to a removal of tonic inhibition arising from SNr GABA interneurons on SNc dopaminergic neurons through the mu opioid receptor (MOR). Long-term morphine exposure produces a series of adaptations in SNc dopamine neurons, which affect neuron excitability and dopamine output to CPu. We have previously shown that dopamine D4 receptor (D4R) stimulation counteracts acute and chronic morphine-induced accumulation of several transcription factors in the CPu (Gago et al., 2011 Brain Res.). Since D4R is expressed in the SNr (Rivera et al., Brain Res. 2003), we postulate that a functional D4R-MOR interaction at the midbrain level could exists. We have investigated the role of D4R in the morphine-induced nigroestriatal dopamine metabolism in the rat brain using biochemical and immunohistochemical techniques. We also have studied the influence of D4R on morphine-induced morphological changes in SNc dopamine neurons using both immunohistochemical and image analysis techniques. Finally, we examined a possible underlying mechanism of the D4R-MOR interaction at the SN level using in vitro quantitative receptor autoradiography. We have found that D4R activation restores dopamine metabolism in the nigroestriatal pathway after acute morphine treatment and prevents morphine-induced rise of tyroxine hydroxylase and dopamine transporter. Rats receiving a continuous treatment of morphine (6 days) showed SNc dopamine neurons with smaller size and higher circularity index compared with the controls animals. These morphine-induced morphological adaptatives changes were prevented when a D4R agonist (PD168,077) was administered at the same time with morphine. Autoradiographic studies demonstrated that the D4R agonist reduce the affinity of MOR. The present study provides evidence for the existence of a fully blocking effect of the D4R on the activation of dopaminergic nigroestriatal pathway by morphine.Financiación: P09-CVI- 4702 (Proyecto de Excelencia de la Junta de Andalucía

Dopamine D-4 receptor counteracts morphine-induced changes in µ opioid receptor signaling in the striosomes of the rat caudate putamen

The mu opioid receptor (MOR) is critical in mediating morphine analgesia. However, prolonged exposure to morphine induces adaptive changes in this receptor leading to the development of tolerance and addiction. In the present work we have studied whether the continuous administration of morphine induces changes in MOR protein levels, its pharmacological profile, and MOR-mediated G-protein activation in the striosomal compartment of the rat CPu, by using immunohistochemistry and receptor and DAMGO-stimulated [S-35]GTP gamma S autoradiography. MOR immunoreactivity, agonist binding density and its coupling to G proteins are up-regulated in the striosomes by continuous morphine treatment in the absence of changes in enkephalin and dynorphin mRNA levels. In addition, co-treatment of morphine with the dopamine D-4 receptor (D4R) agonist PD168,077 fully counteracts these adaptive changes in MOR, in spite of the fact that continuous PD168,077 treatment increases the [H-3]DAMGO B-max values to the same degree as seen after continuous morphine treatment. Thus, in spite of the fact that both receptors can be coupled to G(i/0) protein, the present results give support for the existence of antagonistic functional D4R-MOR receptor-receptor interactions in the adaptive changes occurring in MOR of striosomes on continuous administration of morphine

A selective defect in the glial wedge as part of the neuroepithelium disruption in hydrocephalus development in the mouse hyh model is associated with complete corpus callosum dysgenesis

IntroductionDysgenesis of the corpus callosum is present in neurodevelopmental disorders and coexists with hydrocephalus in several human congenital syndromes. The mechanisms that underlie the etiology of congenital hydrocephalus and agenesis of the corpus callosum when they coappear during neurodevelopment persist unclear. In this work, the mechanistic relationship between both disorders is investigated in the hyh mouse model for congenital hydrocephalus, which also develops agenesis of the corpus callosum. In this model, hydrocephalus is generated by a defective program in the development of neuroepithelium during its differentiation into radial glial cells.MethodsIn this work, the populations implicated in the development of the corpus callosum (callosal neurons, pioneering axons, glial wedge cells, subcallosal sling and indusium griseum glial cells) were studied in wild-type and hyh mutant mice. Immunohistochemistry, mRNA in situ hybridization, axonal tracing experiments, and organotypic cultures from normal and hyh mouse embryos were used.ResultsOur results show that the defective program in the neuroepithelium/radial glial cell development in the hyh mutant mouse selectively affects the glial wedge cells. The glial wedge cells are necessary to guide the pioneering axons as they approach the corticoseptal boundary. Our results show that the pioneering callosal axons arising from neurons in the cingulate cortex can extend projections to the interhemispheric midline in normal and hyh mice. However, pioneering axons in the hyh mutant mouse, when approaching the area corresponding to the damaged glial wedge cell population, turned toward the ipsilateral lateral ventricle. This defect occurred before the appearance of ventriculomegaly.DiscussionIn conclusion, the abnormal development of the ventricular zone, which appears to be inherent to the etiology of several forms of congenital hydrocephalus, can explain, in some cases, the common association between hydrocephalus and corpus callosum dysgenesis. These results imply that further studies may be needed to understand the corpus callosum dysgenesis etiology when it concurs with hydrocephalus