Impulsivity traits in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a demyelinating disease with a lifetime prevalence of 4.41/100000 in Bogota, Colombia. It is known that it can be related with neuropsychiatric disorders, increasing by a factor of three the prevalence of depression in MS patients compared to general population. However, less attention has been given to the association between MS and impulsive behavior. METHODS: This cross-sectional study compared the levels of impulsivity controlling for the presence of MS. 60 patients with MS and 60 sex- and age-matched subjects without MS were included. In order to assess depression and impulsivity, participants completed the 13-item short form of the Beck Depression Inventory (BDI-SF), the self-report Barratt Impulsiveness Scale version 11 (BIS-11) and the Immediate and Delayed Memory Tasks (IMT-DMT) as an objective measure of impulsive behavior. RESULTS: Total scores, motor and cognitive subscales on the BIS-11 were significantly higher in the MS group. However, median BDI-SF score was also higher in MS patients than in subjects without MS (p < 0.001). To rule out depression as a confounding factor, stratification was performed using the BDI-SF score. In the subgroup of individuals with a BDI-SF< 8, the BIS-11 cognitive subscale scores were significantly higher in patients with MS than in subjects without MS (p = 0.041). In the IMT/DMT test, subjects with MS had a fewer number of correct detections than did subjects without MS, after controlling for BDI-SF score (p = 0.0001/p = 0.003). The ratio of commission errors to correct detections in the IMT was significantly higher in the MS group (p = 0.011). CONCLUSION: Patients with MS showed higher levels of cognitive impulsivity than subjects without MS. Objective measures for impulsiveness further support this finding. Impulsiveness scales scores might be biased by depression, which should be considered when assessing impulsivity in MS.

Cocaine withdrawal reduces group I mGluR-mediated long-term potentiation via decreased GABAergic transmission in the amygdala.

Cocaine relapse can occur when cocaine-associated environmental cues induce craving. Conditioned place preference (CPP) is a behavioral paradigm modeling the association between cocaine exposure and environmental cues. The amygdala is involved in cocaine cue associations with the basolateral amygdala (BLA) and central amygdala (CeA) acting differentially in cue-induced relapse. Activation of metabotropic glutamate receptors induces synaptic plasticity, the mechanism of which is thought to underlie learning, memory and drug-cue associations. The goal of this study was to examine the neural alterations in responses to group I metabotropic glutamate receptor (mGluR) agonists in the BLA to lateral capsula of CeA (BLA-CeLc) pathway in slices from rats exposed to cocaine-CPP conditioning and withdrawn for 14 days. mGluR1, but not mGluR5, agonist-induced long-term potentiation (mGluR1-LTP) in the BLA-CeLc pathway was reduced in rats withdrawal from cocaine for 2 and 14 days, and exhibited an altered concentration response to picrotoxin. Cocaine withdrawal also reduced γ-aminobutyric acid (GABA)ergic synaptic inhibition in CeLc neurons. Blocking cannabinoid receptor 1 (CB(1) ) reduced mGluR1-LTP in the saline-treated but not cocaine-withdrawn group. Response to CB(1) but not CB(2) agonist was altered after cocaine. Additionally, increasing endocannabinoid (eCB) levels abolished mGluR1-LTP in the saline but not cocaine-withdrawn group. However, CB(1) and CB(2) protein levels were increased in the amygdala of cocaine-withdrawn rats while mGluR1 and mGluR5 remained unchanged. These data suggested that the mechanisms underlying the diminished mGluR1-LTP in cocaine-withdrawn rats involve an altered GABAergic synaptic inhibition mediated by modulation of downstream eCB signaling. These changes may ultimately result in potentiated responses to environmental cues that would bias behavior toward drug-seeking.

Validity and Reliability of the Abbreviated Barratt Impulsiveness Scale in Spanish (BIS-15S).

OBJECTIVE: This study determined the validity and reliability of a new, abbreviated version of the Spanish Barratt Impulsiveness Scale (BIS-15S) in Colombian subjects. METHOD: The BIS-15S was tested in non-clinical (n=283) and clinical (n=164) native Spanish-speakers. Intra-scale reliability was calculated using Cronbach's α, and test-retest reliability was measured with Pearson correlations. Psychometric properties were determined using standard statistics. A factor analysis was performed to determine BIS-15S factor structure. RESULTS: 447 subjects participated in the study. Clinical subjects were older and more educated compared to non-clinical subjects. Impulsivity scores were normally distributed in each group. BIS-15S total, motor, non-planning and attention scores were significantly lower in non-clinical vs. clinical subjects. Subjects with substance-related disorders had the highest BIS-15S total scores, followed by subjects with bipolar disorders and bulimia nervosa/binge eating. Internal consistency was 0.793 and test-retest reliability was 0.80. Factor analysis confirmed a three-factor structure (attention, motor, non-planning) accounting for 47.87% of the total variance in BIS-15S total scores. CONCLUSIONS: The BIS-15S is a valid and reliable self-report measure of impulsivity in this population. Further research is needed to determine additional components of impulsivity not investigated by this measure.

Rabdomiolisis y falla renal aguda en un paciente con trastorno depresivo recurrente tratado con escitalopram y quetiapina: Case Report / Rhabdomyolysis and Acute Renal Failure in a Recurrent Depressive Patient Treated with Escitalopram and Quetiapine

Objetivo: Describir un caso de rabdomiolisis y falla renal aguda asociado a la administración de quetiapina y escitalopram en un adulto joven en tratamiento por depresión recurrente. Métodos Descripción detallada del paciente y de su enfermedad actual, y revisión no sistemática de la literatura relevante. Resultados: Sujeto de 35 años con antecedentes de trastorno depresivo para el cual recibía escitalopram y quetiapina; presenta síntomas consistentes con rabdomiolisis y falla renal aguda luego de ingerir una sobredosis (900 mg) de quetiapina. La quetiapina y otros antipsicóticos han sido asociados a rabdomiolisis con o sin falla renal aguda. Igualmente, antidepresivos han sido asociados con episodios similares. El mecanismo que media tal asociación no ha sido encontrado. Conclusiones: Los antipsicóticos y los antidepresivos están asociados a rabdomiolisis en individuos con susceptibilidad biológica. Los efectos tóxicos de la serotonina pueden estar involucrados en tal asociación. Lo anterior obliga a su empleo cuidadoso en pacientes en riesgo de hiperfunción serotoninérgica.

Objective: To describe a case of quetipiane- and escitalopram-associated rhabdomyolysis and secondary acute renal failure in a young adult suffering from recurrent depression. Methods: detailed clinical description of the subject's case and relevant literature was reviewed. Results: A 35-year old male suffering from recurrent mayor depression treated with quetiapine and escitalopram, developed rhabdomyolysis and acute renal failure after ingesting an overdose of quetiapine (900 mg). Quetiapine and other antipsychotics have been related with rhabdomyolysis with or without renal failure in association or not with neuroleptic malignant syndromes. Similarly, antidepressant medications, specially venlafaxine but not escitalopram, have been associated with rhabdomyolysis. However, the exact mechanisms involved in this association have are not clear. Conclusions: Antipsychotic and antidepressant medications have been associated with rhabdomyolysis in vulnerable subjects. Serotonin-mediated toxicity has been proposed as a plausible etiological factor in these cases. Thus, psychotropic medications involving this neurotransmitter should be used cautiously in subjects at risk for serotonin hyperactivity.

Validity and reliability of the abbreviated barratt impulsiveness scale in spanish (BIS-15S)

Introduction: This study determined the validity and reliability of a new, abbreviated version of the Spanish Barratt Impulsiveness Scale (BIS-15S) in Colombian subjects. Method: The BIS-15S was tested in non-clinical (n=283) and clinical (n=164) native Spanish-speakers. Intra-scale reliability was calculated using Cronbach’s , and test-retest reliability was measured with Pearson correlations. Psychometric properties were determined using standard statistics. A factor analysis was performed to determine BIS-15S factor structure. Results: 447 subjects participated in the study. Clinical subjects were older and more educated compared to non-clinical subjects. Impulsivity scores were normally distributed in each group. BIS-15S total, motor, non-planning and attention scores were significantly lower in non-clinical vs. clinical subjects. Subjects with substance related disorders had the highest BIS-15S total scores, followed by subjects with bipolar disorders and bulimia nervosa/binge eating. Internal consistency was 0.793 and test-retest reliability was 0.80. Factor analysis conformed a three-factor structure (attention, motor, non-planning) accounting for 47.87% of the total variance in BIS-15S total scores. Conclusions: The BIS-15S is a valid and reliable self-report measure of impulsivity in this population. Further research is needed to determine additional components of impulsivity not investigated by this measure...

Introducción: Determinar la validez y confiabilidad de una nueva versión abreviada de la Escala de Impulsividad de Barratt (BIS-15S) en la población colombiana. Método: El BIS-15S fue aplicado a sujetos hispanoparlantes no clínicos (n=283) y clínicos (n=164). Sus propiedades psicométricas se establecieron con pruebas estadísticas estandarizadas y sus factores principales se analizaron para determinar la estructura de los factores del instrumento. Resultados: 447 sujetos participaron en el estudio. Los sujetos clínicos fueron mayores y más educados que los sujetos no clínicos. Los puntajes estuvieron distribuidos normalmente en las dos poblaciones. Los puntajes total, motor, de no planeación y atención del BIS-15S fueron ignificativamente menores en sujetos no clínicos, comparados con sujetos clínicos. Los puntajes de los sujetos con abuso/dependencia a drogas fueron los más altos, seguidos de aquellos de sujetos con trastornos bipolares y bulimia nerviosa/trastorno por atracones. La consistencia interna del BIS-15S fue 0,793; su confiabilidad prueba-reprueba, 0,80. El análisis de factores conformó tres factores principales (motor, no planeación y atención) responsables de 47,87% de la varianza del puntaje total del BIS-15S. Conclusiones: El BIS-15S es una medida válida y confiable del rasgo impulsividad en la población colombiana. Son necesarios estudios adicionales para establecer otras dimensiones del rasgo no medidas por el instrumento...

La dureza de la ciencia dura: ¿mito o realidad? Elementos para una discusión / The Hardness of Hard Science: Truth or Myth?

Introducción:Discutir aspectos metodológicos relacionados con la calidad de las investigaciones preclínicas y la aplicabilidad de principios de investigación clínica y medicina basada en la evidencia para evaluar la validez y calidad de los estudios preclínicos. Método: Análisis crítico de publicaciones selectas. Resultados: El ejercicio de la investigación (preclínica y clínica) exige indicadores rigurosos que permitan determinar la validez y generalización de sus hallazgos. Es deseable el desarrollo de metodologías para determinar su peso y hacer posible su revisión sistemática. Conclusiones: Se exige un replanteamiento del que hacer científico, a la luz del reconocimiento de sus limitaciones, la urgencia de sus aportes y la responsabilidad que esta tiene frente al bienestar de la humanidad...

Introduction: To discuss methodological issues concerning the quality and applicability of clinical research and evidence-based medicine principles to pre-clinical research. Methods: Critical analysis of selected writings. Results: Rigorous standards to determine the quality and generalization of pre-clinical fiindings are needed; methods to systematically review the evidence and its weight have not been developed for pre-clinical research. Conclusions: Never before has a debate about the limitations of pre-clinical research been more relevant, given the omentousness of its contributions and its obligation towards the well-being of humankind...

Internet y recursos en línea como alternativas terapéuticas para trastornos de abuso o dependencia a sustancias: una revisión de los recursos disponibles / Internet and online resources such as therapeutic alternatives for substance use disorders: a review of available resources

Introducción: Las intervenciones en línea constituyen una de las tantas opciones terapéuticas disponibles para pacientes con trastornos por abuso/dependencia a sustancias y otras condiciones psiquiátricas. No obstante, su utilidad ha sido ampliamente cuestionada a la luz de falta de rigurosidad. Objetivo: Revisar y discutir la literatura existente acerca de los recursos e intervenciones en línea para trastornos por abuso/dependencia de sustancias psicoactivas. Método: Búsqueda sistemática de literatura sobre los recursos e intervenciones en línea relacionados con trastornos por abuso/dependencia a sustancias. Resultados: Existen numerosos recursos informativos para el público general, pero la calidad de la información disponible no es siempre adecuada. También hay, aunque en menor número, intervenciones y programas de autoayuda en línea, específicamente para tabaquismo y alcoholismo. No obstante, su efectividad no ha sido determinada en estudios clínicos aleatorizados y controlados, adecuadamente diseñados. Conclusión: Son necesarios estudios clínicos aleatorizados y controlados que permitan evaluar la efectividad de este tipo de intervenciones. Los resultados iluminarán el desarrollo de estrategias de intervención integrales que usen esta poderosa herramienta de comunicación...

Introduction: Online interventions are one of the many treatment options available for patients with substance use disorders and other psychiatric conditions. However, its usefulness has been widely questioned due to a lack of rigorous scientific research. Objective: To review and discuss the literature about online resources and interventions for substance use disorders. Methods: Systematic search of literature on online resources and interventions related to substance use disorders. Results: There are many sources of information for the general public, but the quality of information available is not always appropriate. There are, though in smaller numbers, interventions and online self-help programs specifically for smoking and alcoholism. However, their effectiveness has not been determined in properly designed randomized controlled trials. Conclusion: It is necessary to evaluate the safety and efficacy of online interventions using rigorous randomized controlled trials. The results illuminate the development of comprehensive intervention strategies that may use this powerful communication tool...

Efectos neurobiológicos de la psicoterapia / Neurobiologic effects of psycotherapy / Efeitos neurobiologicos da psicoterapia

La psicoterapia permanece como una opción de tratamiento vigente en diversos tipos de trastornos psiquiátricos. Aunque su efectividad ha sido ampliamente demostrada desde hace mas de dos décadas, los mecanismo biológicos mediante los cuales ejerce un efecto sobre el funcionamiento cerebral del paciente y su comportamiento, continúan siendo desconocidos. En este artículo se revisan los posibles mecanismos que median su efecto sobre el funcionamiento cerebral, entre ellos las bases celulares y moleculares de la memoria, las modificaciones en los sistemas neurotransmisores y la plasticidad sináptica. La revisión de la evidencia acumulada permite sugerir que la psicoterapia ejerce un efecto neurofisiológico al mismo nivel de los fármacos con acción psicotrópica, no obstante, diferencias en especificidad regional y de sistema blanco pueden explicar las diferencias que se observan entre estas dos formas de tratamiento...

Psychotherapy remains an effective option in the treatment of diverse types of psychiatric disorders. Although its effectiveness has been widely demonstrated for more than two decades, the biological mechanisms by means of which it exerts an effect over the brain function and the patient's behavior, continues to be unknown. In this article we review the possible mechanisms that mediate its effect on the brain function, among them the cellular and molecular bases of memory, the modifications in the neurotransmitter systems and the synaptic plasticity. The review of the accumulated evidence allows us to suggest that psychotherapy exerts a neurophysiologic effect at the same level of psychotropic drugs; however, differences in regional specificity and of the white system may explain the differences that are observed between these two forms of treatment...

A psicoterapia permanece como uma opção vigente de tratamento em tipos diversos de transtornos psiquiátricos. Embora sua eficácia seja demonstrada extensamente por mais de duas décadas, o mecanismo biológico por meio de qual exerce um efeito na função cerebral do paciente e de seu comportamento, continua sendo desconhecido. Neste artigo são revistos os possíveis mecanismos que mediam seu efeito na função cerebral, entre eles as bases celulares e moleculares da memória, as modificações nos sistemas neurotransmissores e a plasticidade sináptica. A revisão da evidência acumulada permite sugerir que a psicoterapia exerce um efeito neurofisiológico ao mesmo nível que os fármacos com ação psicotrópica, entretanto, diferenças em especificidade regional e do sistema branco podem explicar as diferenças que são observadas entre estas dois formas do tratamento...

Obsessive-Compulsive Disorder Symptoms in Huntington’s Disease: A Case Report / Síntomas del trastorno obsesivocompulsivo en la enfermedad de Huntington: reporte de caso

Introduction: Few cases of obsessive-compulsive disorder (OCD) symptoms preceding the clinical onset of Huntington Disease (HD) or during later stages of the disease have been reported in the literature, but the nature of this association and its neurobiological mechanisms have not been well-investigated. Objectives: To review the scientific literature regarding OCD symptoms in patients with HD and describe a case study from our clinic. Methods: Extensive literature searches were performed to identify reports of patients with concurrent HD and OCD symptoms. Results: Recent studies and the current case report suggest that OCD symptoms may predate or coincide with motor, affective or behavioral symptoms in patients with HD. The development of OCD and HD symptoms may involve structural and functional changes affecting the orbital and medial prefrontal cortex, ventromedial caudate nucleus, and pallidal sites. Conclusions: Some patients with HD develop symptoms associated with OCD. Progressive and differential neuropathological changes in the ventromedial caudate nucleus and related neural circuits may underlie this association. No specific treatment strategy has been developed to treat these patients; however some medications attenuate associated symptoms. Further testing is needed to determine the neurobiological mechanisms of these disorders.

Introducción: Algunos reportes de caso indican que pacientes con enfermedad de Huntington (EH) pueden presentar síntomas obsesivo-compulsivos (TOC) antes del desarrollo de la enfermedad y durante ésta, pero no se ha estudiado la naturaleza de esta asociación y sus mecanismos neurobiológicos. Objetivos: Revisar la literatura científica acerca de la asociación entre EH y síntomas TOC y reportar el caso de un paciente con estas condiciones. Método: Búsqueda selectiva de literatura relevante. Resultados: Estudios recientes y el caso aquí reportado sugieren que los síntomas TOC pueden presentarse antes de la EH y durante ésta. El desarrollo concurrente de estas patologías puede estar mediado por cambios estructurales y funcionales de la corteza prefrontal orbital y medial, región ventromedial del núcleo caudado y regiones palidales. Conclusiones: Algunos pacientes con EH desarrollan síntomas de TOC. Cambios neuropatológicos progresivos y diferenciales en el caudado ventromedial y circuitos dependientes pueden mediar esta asociación. No se ha desarrollado una estrategia terapéutica para el tratamiento de estos pacientes; sin embargo, algunos medicamentos parecen ofrecer mejoría sintomática parcial a los sujetos afectados. Se requieren mayores estudios acerca de los mecanismos neuropatológicos involucrados en esta asociación.

Synaptic physiology of central CRH system.

Corticotropin-Releasing Hormone (CRH) or Corticotropin-Releasing Factor (CRF) and its family of related naturally occurring endogenous peptides and receptors are becoming recognized for their actions within central (CNS) and peripheral (PNS) nervous systems. It should be recognized that the term 'CRH' has been displaced by 'CRF' [Guillemin, R., 2005. Hypothalamic hormones a.k.a. hypothalamic releasing factors. J. Endocrinol. 184, 11-28]. However, to maintain uniformity among contributions to this special issue we have used the original term, CRH. The term 'CRF' has been associated recently with CRH receptors and designated with subscripts by the IUPHAR nomenclature committee [Hauger, R.L., Grigoriadis, D.E., Dallman, M.F., Plotsky, P.M., Vale, W.W., Dautzenberg, F.M., 2003. International Union of Pharmacology. XXXVI. Corticotrophin-releasing factor and their ligands. Pharmacol. Rev. 55, 21-26] to denote the type and subtype of receptors activated or antagonized by CRH ligands. CRH, as a hormone, has long been identified as the regulator of basal and stress-induced ACTH release within the hypothalamo-pituitary-adrenal axis (HPA axis). But the concept, that CRH and its related endogenous peptides and receptor ligands have non-HPA axis actions to regulate CNS synaptic transmission outside the HPA axis, is just beginning to be recognized and identified [Orozco-Cabal, L., Pollandt, S., Liu, J., Shinnick-Gallagher, P., Gallagher, J.P., 2006a. Regulation of Synaptic Transmission by CRF Receptors. Rev. Neurosci. 17, 279-307; Orozco-Cabal, L., Pollandt, S., Liu, J., Vergara, L., Shinnick-Gallagher, P., Gallagher, J.P., 2006b. A novel rat medial prefrontal cortical slice preparation to investigate synaptic transmission from amygdala to layer V prelimbic pyramidal neurons. J. Neurosci. Methods 151, 148-158] is especially noteworthy since this synapse has become a prime focus for a variety of mental diseases, e.g. schizophrenia [Fischbach, G.D., 2007. NRG1 and synaptic function in the CNS. Neuron 54, 497-497], and neurological disorders, e.g., Alzheimer's disease [Bell, K.F., Cuello, C.A., 2006. Altered synaptic function in Alzheimer's disease. Eur. J. Pharmacol. 545, 11-21]. We suggest that "The Stressed Synapse" has been overlooked [c.f., Kim, J.J., Diamond, D.M. 2002. The stressed hippocampus, synaptic plasticity and lost memories. Nat. Rev., Neurosci. 3, 453-462; Radley, J.J., Morrison, J.H., 2005. Repeated stress and structural plasticity in the brain. Ageing Res. Rev. 4, 271-287] as a major contributor to many CNS disorders. We present data demonstrating CRH neuroregulatory and neuromodulatory actions at three limbic synapses, the basolateral amygdala to central amygdala synapse; the basolateral amygdala to medial prefrontal cortex synapse, and the lateral septum mediolateral nucleus synapse. A novel stress circuit is presented involving these three synapses. We suggest that CRH ligands and their receptors are significant etiological factors that need to be considered in the pharmacotherapy of mental diseases associated with CNS synaptic transmission.

Dopamine and corticotropin-releasing factor synergistically alter basolateral amygdala-to-medial prefrontal cortex synaptic transmission: functional switch after chronic cocaine administration.

Basolateral amygdala (BLA) neurons provide a major excitatory input to medial prefrontal cortex (mPFC)-layer V pyramidal neurons. Under stressful conditions, commonly associated with chronic cocaine abuse, altered BLA-to-mPFC synaptic transmission could lead to defective emotional information processing and decision making within the mPFC and result in misguided and inappropriate behaviors. We examined the effects of cocaine administered chronically in vivo on EPSCs recorded from a putative BLA-mPFC pathway in vitro and their modulation by dopamine (DA), corticotropin-releasing factor (CRF), and their combination (DA plus CRF). In saline-treated animals, activation of D(1/5) receptors depressed BLA-mPFC EPSCs, whereas CRF1 receptor activation alone had no effect on EPSCs. Activating D(1/5) and CRF1 receptors in combination, however, worked synergistically through presynaptic and postsynaptic mechanisms to depress EPSCs to levels greater than D(1/5) receptor activation alone. After chronic cocaine administration, the function of DA(1/5) and CRF receptors switched from inhibitory to excitatory. In slices from cocaine-treated animals, putative BLA-mPFC EPSCs were depressed through a presynaptic mechanism. Now, activation of either D(1/5) or CRF2 receptors increased the cocaine-induced, depressed EPSCs. Additionally, simultaneous activation of presynaptic D(1/5) and CRF2 receptors led to further enhancement of EPSCs. These data indicate that CRF acting synergistically with DA normally potentiates D(1/5)-induced synaptic depression. However, after chronic cocaine, the combined synergistic actions of DA and CRF switched polarity to enhance facilitation of BLA-mPFC glutamatergic transmission. Also unmasked after acute withdrawal from chronic cocaine are endogenous, tonic-inhibitory D2-like and tonic-facilitatory CRF2 receptor actions. These multiple functional and receptor changes may underlie the altered, possibly aberrant, decision-making process after chronic cocaine.

Neurobiología de la impulsividad y los trastornos de la conducta alimentaria.

INTRODUCTION: Impulsivity is a complex personality trait related to the control of behavior and emotions and it is present in a wide variety of psychiatric diseases, including eating disorders and particularly in bulimia nervosa (BN). Yet, the relationship between impulsivity and bulimia nervosa, as well as the neurobiological substrates of these disorders, are difficult to discern. OBJECTIVES: The present manuscript reviews the neural substrates for impulsivity, including executive function, preference formation and emotional regulation, and the function of these circuits in individuals with BN. METHODS: A selective review of the literature related to the subject was performed. RESULTS AND CONCLUSIONS: The discussion illustrates the complex relationship between impulsivity and BN, where impulsivity may serve as a vulnerability factor that sensitizes the subjects with BN to negative emotional states that bias the impact of environmental and internal stimuli over behavioral regulation processes, favoring maladaptive and inflexible behavioral patterns.

Obsessive-Compulsive Disorder Symptoms in Huntington's Disease: A Case Report.

INTRODUCTION: Few cases of obsessive-compulsive disorder (OCD) symptoms preceding the clinical onset of Huntington Disease (HD) or during later stages of the disease have been reported in the literature, but the nature of this association and its neurobiological mechanisms have not been well-investigated. OBJECTIVES: To review the scientific literature regarding OCD symptoms in patients with HD and describe a case study from our clinic. METHODS: Extensive literature searches were performed to identify reports of patients with concurrent HD and OCD symptoms. RESULTS: Recent studies and the current case report suggest that OCD symptoms may predate or coincide with motor, affective or behavioral symptoms in patients with HD. The development of OCD and HD symptoms may involve structural and functional changes affecting the orbital and medial prefrontal cortex, ventromedial caudate nucleus, and pallidal sites. CONCLUSIONS: Some patients with HD develop symptoms associated with OCD. Progressive and differential neuropathological changes in the ventromedial caudate nucleus and related neural circuits may underlie this association. No specific treatment strategy has been developed to treat these patients; however some medications attenuate associated symptoms. Further testing is needed to determine the neurobiological mechanisms of these disorders.

Implicaciones prra el estudio de la neurobiologa de la experiencia consciente.. el acto impulsivo / Neurobiology o cconscious experience: implication of impulsive behavior

Consciousness and impulsivity are multidimensional constructs related to the control of thoughts and behavior. Impulsivity is a complex personality trait characterized by: acting without thinking, inability to plan ahead of time and poor attention or vigilance. Consciousness is a construct that encompasses a variety of physiological processes related to the experience of awareness and the acquisition of knowledge in human beings. With respect to the control of human behavior, consciousness and impulsivity appear to be related to opposite behaviors. Historically, efforts to understand these constructs by different disciplines have resulted in the development of divergent definitions and a variety of measures, thus causing confusion. The purposes of this article are to: 1) describe examples of solutions to this confusion within impulsivity research and discuss how consciousness research can benefit from the study of impulsivity; 2) discuss how consciousness and impulsivity can be measured within a laboratory and treated as experimental variables; 3) Summarize the lessons learned by comparing impulsive and premeditated acts from an integrated, multidimensional perspective; 4) Discuss the implications of a multidisciplinary model for pursuing consciousness research.

Conciencia e impulsividad son dos constructos multidimensionales relacionados con el control del pensamiento y comportamiento humano. Impulsividad es un rasgo de personalidad complejo caracterizado por una elevada tendencia a actuar sin pensar, incapacidad para planear actividades futuras y disminución de la capacidad de concentración. Conciencia por su parte, es un constructo que cobija una serie de procesos fisiológicos relacionados con la generación de experiencia conciente y la adquisición de conocimientos. Con respecto al control sobre la acción humana, conciencia e impulsividad parece estar relacionados con comportamientos opuestos. Históricamente, los esfuerzos realizados por diversas disciplinas con el fin de estudiar estos constructos han llevado al desarrollo de definiciones divergentes y a una serie de medidas, causando una mayor confusión. Los propósitos de este artículo son: 1) describir ejemplos de posibles soluciones al estado de confusión en el campo de la investigación sobre impulsividad y discutir como el estudio de la conciencia puede beneficiarse de la investigación de la impulsividad; 2) discutir algunas de las maneras utilizadas para medir impulsividad en el laboratorio y cómo hacer de estos constructos variables experimentales; 3) resumir algunas de las lecciones derivadas de la comparación de los actos impulsivos con los premeditados desde una perspectiva integral y multidimensional; 4) discutir las implicaciones derivadas del uso de un enfoque multidimensional para el estudio de la conciencia.

Long-term potentiation (LTP) in the central amygdala (CeA) is enhanced after prolonged withdrawal from chronic cocaine and requires CRF1 receptors.

The amygdala is part of the brain reward circuitry that plays a role in cocaine-seeking and abstinence in animals and cocaine craving and relapse in humans. Cocaine-seeking is elicited by cocaine-associated cues, and the basolateral amygdala (BLA) and CeA are essential in forming and communicating drug-related associations that are thought to be critical in long-lasting relapse risk associated with drug addiction. Here we simulated a cue stimulus with high-frequency stimulation (HFS) of the BLA-CeA pathway to examine mechanisms that may contribute to drug-related associations. We found enhanced long-term potentiation (LTP) after 14-day but not 1-day withdrawal from 7-day cocaine treatment mediated through N-methyl-d-aspartate (NMDA) receptors (NRs), L-type voltage-gated calcium channels (L-VGCCs), and corticotropin-releasing factor (CRF)(1) receptors; this was accompanied by increased phosphorylated NR1 and CRF(1) protein not associated with changes in NMDA/AMPA ratios in amygdalae from cocaine-treated animals. We suggest that these signaling mechanisms may provide therapeutic targets for the treatment of cocaine cravings.

Cocaine withdrawal enhances long-term potentiation induced by corticotropin-releasing factor at central amygdala glutamatergic synapses via CRF, NMDA receptors and PKA.

Cocaine addiction is an enduring, relapsing, behavioural disorder in which stressors reinstate cocaine-seeking even after prolonged abstinence. Evidence suggests that the 'anxiety-like' behaviour and stress associated with protracted withdrawal may be mediated by increased corticotropin-releasing factor (CRF) in the central nucleus of the amygdala (CeA), a part of the limbic circuitry engaged in the coding and transmission of stimulus-reward associations. In the present study we describe a long-lasting potentiation of glutamatergic transmission induced at lateral amygdala (LA)-to-CeA synapses by rat/human CRF. After 2 weeks of withdrawal from repeated intermittent exposure to cocaine, CRF-induced long-term potentiation (LTP) was greatly enhanced compared to the respective saline control group while, after short-term withdrawal (24 h), there was no significant difference between the two treatment groups, indicating alterations in CRF systems during protracted withdrawal from chronic cocaine. After prolonged withdrawal, CRF-induced LTP was dependent on activation of CRF2, CaV2.3 (R-type) calcium channels and intracellular signalling through protein kinase C in both saline- and cocaine-treated groups. The enhanced CRF-induced LTP after 2 weeks of withdrawal was mediated through augmented CRF1 receptor function, associated with an increased signalling through protein kinase A, and required N-methyl-D-aspartate (NMDA) receptors. Accordingly, single-cell recordings revealed a significantly increased NMDA/AMPA ratio after prolonged withdrawal from the cocaine treatment. These results support a role for CRF1 receptor antagonists as plausible treatment options during withdrawal from chronic cocaine and suggest Ca(V)2.3 blockers as potential candidates for pharmaceutical modulation of CRF systems.

Regulation of synaptic transmission by CRF receptors.

Corticotropin-releasing factor (CRF or CRH) and its family of related peptides have long been recognized as hypothalamic-pituitary-adrenal (HPA) axis peptides that function to regulate the release of other hormones, e.g., ACTH. In addition, CRF acts outside the HPA axis not as a hormone, but as a regulator of synaptic transmission, pre- and post-synaptically, within specific CNS neuronal circuits. Synaptic transmission within the nervous system is today understood to be a more complex process compared to the concepts associated with the term 'synapse' introduced by Sherrington in 1897. Based on more than a century of progress with modern cellular and molecular experimental techniques, prior definitions and functions of synaptic molecules and their receptors need to be reconsidered (see Glossary and Fig. 1), especially in light of the important roles for CRF, its family of peptides and other potential endogenous regulators of neurotransmission, e.g., vasopressin, NPY, etc. (see Glossary). In addition, the property of 'constitutive activity' which is associated with G-protein coupled receptors (GPCRs) provides a persistent tonic mechanism to fine-tune synaptic transmission during both acute and chronic information transfer. We have applied the term 'regulator', adapted from the hormone literature, to CRF, as an example of a specific endogenous substance that functions to facilitate or depress the actions of neuromodulators on fast and slow synaptic responses. As such, synaptic neuroregulators provide a basic substrate to prime or initiate silently plastic processes underlying neurotransmitter-mediated information transfer at CNS synapses. Here we review the role of CRF to regulate CNS synaptic transmission and also suggest how under a variety of allostatic changes, e.g., associated with normal plasticity, or adaptations resulting from mental disorders, the synaptic regulatory role for CRF may be 'switched' in its polarity and/or magnitude in order to provide a coping mechanism to deal with daily and life-long stressors. Thus, a prominent role we assign to non-HPA axis CRF, its family of peptides, and their receptors, is to maintain both acute and chronic synaptic stability.

A novel rat medial prefrontal cortical slice preparation to investigate synaptic transmission from amygdala to layer V prelimbic pyramidal neurons.

Electrophysiological recordings from identified synapses in CNS slice preparations in vitro provide important information regarding the connectivity of neuronal circuits and the underlying cellular mechanisms responsible for neuronal excitability and synaptic transmission. We present an anatomical, electrophysiological, and pharmacological characterization of a novel brain slice preparation (BLA-mPFC) to investigate basolateral amygdala synaptic input to rat layer V medial prefrontal cortex pyramidal neurons. A fluorescent tracer (DiI) unilaterally infused in vivo into the basolateral amygdala was used to detect amygdala efferent fibers innervating layer V of the prelimbic and infralimbic cortices within prefrontal cortex slices. In vitro, evoked synaptic responses elicited by stimulating identified basolateral amygdala pathway terminals within the acute BLA-mPFC slice preparation yielded monosynaptic excitatory postsynaptic responses in layer V pyramidal neurons from the prelimbic cortex as determined by extracellular and intracellular recordings. The BLA-mPFC preparation provides essential knowledge of amygdaloid input to the medial prefrontal cortex where information from various brain areas is integrated and returned to subcortical structures, such as the amygdala itself. In addition to investigating normal synaptic function, this preparation provides opportunities to investigate this synapse in animals which have received drugs chronically or have been manipulated genetically to model specific mental diseases known to involve prefrontal cortex and/or amygdala pathology (e.g., schizophrenia, addiction, anxiety, and depression).

Chronic cocaine administration switches corticotropin-releasing factor2 receptor-mediated depression to facilitation of glutamatergic transmission in the lateral septum.

Corticotropin-releasing factor (CRF) and urocortin (Ucn I) are endogenous members among a family of CRF-related peptides that activate two different and synaptically localized G-protein-coupled receptors, CRF1 and CRF2. These peptides and their receptors have been implicated in stress responses and stress with cocaine abuse. In this study, we observed significant alterations in excitatory transmission and CRF-related peptide regulation of excitatory transmission in the lateral septum mediolateral nucleus (LSMLN) after chronic cocaine administration. In brain slice recordings from the LSMLN of control (saline-treated) rats, glutamatergic synaptic transmission was facilitated by activation of CRF1 receptors with CRF but was depressed after activation of CRF2 receptors with Ucn I. After acute withdrawal from a chronic cocaine administration regimen, CRF1 activation remained facilitatory, but CRF2 activation facilitated rather than depressed LSMLN EPSCs. These alterations in CRF2 effects occurred through both presynaptic and postsynaptic mechanisms. In saline-treated rats, CRF1 and CRF2 coupled predominantly to protein kinase A signaling pathways, whereas after cocaine withdrawal, protein kinase C activity was more prominent and likely contributed to the CRF2-mediated presynaptic facilitation. Neither CRF nor Ucn I altered monosynaptic GABA(A)-mediated IPSCs before or after chronic cocaine administration, suggesting that loss of GABAA-mediated inhibition could not account for the facilitation. This switch in polarity of Ucn I-mediated neuromodulation, from a negative to positive regulation of excitatory glutamatergic transmission after chronic cocaine administration, could generate an imbalance in the brain reward circuitry associated with the LSMLN.