Involvement of prelimbic medial prefrontal cortex in panic-like elaborated defensive behaviour and innate fear-induced antinociception elicited by GABAA receptor blockade in the dorsomedial and ventromedial hypothalamic nuclei: role of the endocannabinoid CB1 receptor.

It has been shown that GABAA receptor blockade in the dorsomedial and ventromedial hypothalamic nuclei (DMH and VMH, respectively) induces elaborated defensive behavioural responses accompanied by antinociception, which has been utilized as an experimental model of panic attack. Furthermore, the prelimbic (PL) division of the medial prefrontal cortex (MPFC) has been related to emotional reactions and the processing of nociceptive information. The aim of the present study was to investigate the possible involvement of the PL cortex and the participation of local cannabinoid CB1 receptors in the elaboration of panic-like reactions and in innate fear-induced antinociception. Elaborated fear-induced responses were analysed during a 10-min period in an open-field test arena. Microinjection of the GABAA receptor antagonist bicuculline into the DMH/VMH evoked panic-like behaviour and fear-induced antinociception, which was decreased by microinjection of the non-selective synaptic contact blocker cobalt chloride in the PL cortex. Moreover, microinjection of AM251 (25, 100 or 400 pmol), an endocannabinoid CB1 receptor antagonist, into the PL cortex also attenuated the defensive behavioural responses and the antinociception that follows innate fear behaviour elaborated by DMH/VMH. These data suggest that the PL cortex plays an important role in the organization of elaborated forward escape behaviour and that this cortical area is also involved in the elaboration of innate fear-induced antinociception. Additionally, CB1 receptors in the PL cortex modulate both panic-like behaviours and fear-induced antinociception elicited by disinhibition of the DMH/VMH through microinjection of bicuculline.

Connexions between the dorsomedial division of the ventromedial hypothalamus and the dorsal periaqueductal grey matter are critical in the elaboration of hypothalamically mediated panic-like behaviour.

The electrical and chemical stimulation of the dorsal periaqueductal grey matter (dPAG) elicits panic-like explosive escape behaviour. Although neurons of the ventromedial hypothalamus (VMH) seem to organise oriented escape behaviour, when stimulated with excitatory amino acids at higher doses, non-oriented/explosive escape reactions can also be displayed. The aim of this work was to examine the importance of reciprocal projections between the VMH and the dPAG for the organisation of this panic-like behaviour. The chemical stimulation of the VMH with 9nmol of N-methyl-d-aspartic acid (NMDA) elicited oriented and non-oriented escape behaviours. The pretreatment of the dPAG with a non-selective blocker of synaptic contacts, cobalt chloride (CoCl2), followed by stimulation of the dorsomedial part of the ventromedial hypothalamus (dmVMH) with 9nmol of NMDA, abolished the non-oriented/explosive escape and freezing responses elicited by the stimulation of the dmVMH. Nonetheless, the rats still showed oriented escape to the burrow. On the other hand, when the blockade of the dmVMH with CoCl2 was followed by stimulation of the dPAG with 6nmol of NMDA, no effect was observed either on the non-oriented/explosive escape or on the freezing behaviour organised by the dPAG. Furthermore, Fos protein-labelled neurons were observed in the dPAG after the stimulation of the dmVMH with 9nmol of NMDA. Additionally, when the anterograde neurotracer biotinylated dextran amine (BDA) was deposited in the dmVMH subsequent stimulation of the dmVMH produced BDA-labelled neural fibres with terminal boutons surrounding Fos-labelled neurons in the dPAG, suggesting synaptic contacts between dmVMH and dPAG neurons for eliciting panic-like behavioural responses. The current data suggest that the dPAG is the key structure that organises non-oriented/explosive escape reactions associated with panic attack-like behaviours.

Modelos neuropsicobiológicos para estudo da dor e das emoções / Neuropsychobiological models for the study of pain and emotions / Modelos neuropsicológicos para el estudio del dolor y las emociones

Dor é uma experiência pessoal e subjetiva que pode apenas ser sentida pelo sofredor. A dor aguda tem a finalidade de avisar o indivíduo que algo está errado. Contudo, a dor crônica (DC) é um problema global de saúde, que afeta a qualidade de vida e torna o indivíduo parcial ou totalmente incapacitado. A pesquisa básica utiliza diversos modelos animais para o estudo da dor aguda ou crônica, bem como para o estudo das principais comorbidades oriundas de sua cronificação como a ansiedade e a depressão. Esta revisão aborda os modelos animais mais comumente utilizados neste contexto.

Pain is a personal and subjective experience that can only be felt by the sufferer. Acute pain is intended to warn the individual that something is wrong. However, chronic pain (CP) is a global health problem, affecting the quality of life and making the individual parts or disabled. Basic research uses several animal models for the study of acute or chronic pain, as well as for the study of the main comorbidities arising from their chronicity, such as anxiety and depression. This review focuses on the animal models most commonly used in this context.

El dolor es una experiencia personal y subjetiva que solo puede sentir la víctima. El dolor agudo está destinado a advertir al individuo que algo está mal. Sin embargo, el dolor crónico (EC) es un problema de salud global, que afecta la calidad de vida y hace que el individuo esté parcial o totalmente discapacitado. La investigación básica utiliza varios modelos animales para el estudio del dolor agudo o crónico, así como para el estudio de las principales comorbilidades resultantes de su cronicidad, como la ansiedad y la depresión. Esta revisión se centra en los modelos animales más utilizados en este contexto.

Esquizofrenia e cognição: entendendo as dimensões atencionais, perceptuais e mnemônicas da esquizofrenia / Schizophrenia and cognition: understanding the attentional, perceptual and mnemonic dimensions of schizophrenia / Esquizofrenia y cognición: comprensión de las dimensiones atencional, perceptivas y mnemotécnicas de la esquizofrenia

A esquizofrenia é um transtorno mental grave e incapacitante que tem como critérios diagnósticos sintomas positivos, negativos, discurso e pensamento desorganizado ou catatônico. Cursa com importantes disfunções cognitivas com impactos na atenção, na função executiva, em memória operacional e de trabalho, entre outras. Tais déficits podem estar presentes antes dos sintomas positivos ou mesmo, de maneira subsindrômica desde a infância desses indivíduos. A hipótese dopaminérgica é a mais aceita na gênese das disfunções neuroquímicas, mas há cada vez mais evidência do envolvimento de outros sistemas como o glutamatérgico e o serotoninérgico. No que se refere especificamente aos déficits cognitivos, destacam-se disfunções em córtex pré-frontal, especialmente sua porção dorsolateral e suas conexões com o hipocampo. Entende-se ainda que é muito importante a avaliação cognitiva das pessoas acometidas por essa patologia e existem baterias de testes neuropsicológicos disponíveis como é o caso do Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) e de testes validados no Brasil como o Brief Assessment of Cognition in Schizophrenia (BACS). Tendo em vista a elevada perda de funcionalidade e qualidade de vida desses pacientes, sobretudo daqueles mais acometidos na capacidade cognitiva, há uma necessidade de maiores esforços para o entendimento desse complexo transtorno com vistas a tratamentos mais eficazes e até mesmo desenvolvimento de estratégias preventivas.

Schizophrenia is a serious and disabling mental disorder whose diagnostic criteria are positive or negative symptoms, disorganized or catatonic speech and thinking. It takes place with important cognitive dysfunctions with impacts on attention, executive function, working memory, among others. Such deficits may be present before positive symptoms or even, in a subsyndromal manner since the childhood of these individuals. The dopaminergic hypothesis is the most accepted in the genesis of neurochemical disorders, but there is increasing evidence of the involvement of other systems such as glutamatergic and serotonergic. With regard specifically to cognitive deficits, dysfunctions in the prefrontal cortex stand out, especially its dorsolateral portion and its connections with the hippocampus. It is also understood that the cognitive test of people affected by this pathology is very important and there are neuropsychological tests batteries available, such as Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and tests validated in Brazil such as the Brief Assessment of Cognition in Schizophrenia (BACS). Considering the high loss of functionality and life quality of these patients, especially those more affected in cognitive ability, there is a need for greater efforts to understand this complex disorder aiming more effective treatments and even the development of preventive strategies.

La esquizofrenia es un trastorno mental grave e incapacitante cuyos criterios de diagnóstico son síntomas positivos, negativos, habla y pensamiento desorganizados o catatónicos. Se lleva a cabo con importantes disfunciones cognitivas con impactos en la atención, la función ejecutiva, el trabajo y la memoria de trabajo, entre otros. Tales déficits pueden estar presentes antes de los síntomas positivos o incluso, de manera subsindrómica desde la infancia de estos individuos. La hipótesis dopaminérgica es la más aceptada en la génesis de los trastornos neuroquímicos, pero cada vez hay más evidencia de la participación de otros sistemas como el glutamatérgico y el serotoninérgico. Con respecto específicamente a los déficits cognitivos, se destacan las disfunciones en la corteza prefrontal, especialmente su porción dorsolateral y sus conexiones con el hipocampo. También se entiende que la evaluación cognitiva de las personas afectadas por esta patología es muy importante y hay baterías de pruebas neuropsicológicas disponibles, como la Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) y pruebas validadas en Brasil como el Brief Assessment of Cognition in Schizophrenia (BACS). En vista de la alta pérdida de funcionalidad y calidad de vida de estos pacientes, especialmente los más afectados por la capacidad cognitiva, existe la necesidad de realizar mayores esfuerzos para comprender este complejo trastorno con miras a tratamientos más efectivos e incluso el desarrollo de estrategias preventivas.