RESUMEN
This study investigated the effect of α-adrenoceptor agonists microinjected into the shell region of the accumbens nucleus (AcbSh) on feeding and anxiety-related behaviors in free-feeding rats. Male Wistar rats with a chronically implanted cannula into the AcbSh were unilaterally microinjected with either clonidine (CLON, α(2)-adrenoceptor agonist) or phenylephrine (PHEN, α(1)-adrenoceptor agonist) at the doses of 6 and 20 nmol and submitted to the elevated plus-maze (EPM), a pre-clinical test of anxiety. Immediately after the EPM test, the animals underwent food intake evaluation for 30 min. The data showed that rats microinjected with CLON (20 nmol/0.2 µl) into the AcbSh exhibited increased %Open arm time, which is compatible with an anxiolytic-like effect. The CLON-induced anxiolysis was corroborated by increased head-dipping and decreased stretched-attend posture, two ethologically derived behaviors which are fear/anxiety-motivated. The animal's locomotor activity was not changed by 20 nmol CLON microinjection into the AcbSh. However, neither dose of PHEN microinjected into the AcbSh was able to alter either the spatial-temporal or ethological variables representative of fear/anxiety and locomotion. Food intake was not altered by any dose of CLON and PHEN microinjected into the AcbSh, but the 20 nmol CLON microinjection induced increased motor activity in the feeding test. The data suggests that noradrenergic projections to the AcbSh may underlie fear/anxiety modulation through α(2)-adrenoceptor in the AcbSh, while feeding behavior was unaffected by noradrenergic modulation in the AcbSh of free-feeding rats. This article is part of a Special Issue entitled 'Anxiety and Depression'.
Asunto(s)
Agonistas alfa-Adrenérgicos/farmacología , Ansiedad/inducido químicamente , Ingestión de Alimentos/efectos de los fármacos , Miedo/efectos de los fármacos , Núcleo Accumbens/efectos de los fármacos , Análisis de Varianza , Animales , Clonidina/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Microinyecciones , Núcleo Accumbens/fisiología , Fenilefrina/farmacología , Ratas , Ratas WistarRESUMEN
This study investigated the role of MnR α1-adrenergic receptors in the control of anxiety-like and feeding behaviors and attempted to reveal a possible functional association between both behaviors. The α1-adrenergic agonist phenylephrine (PHE) (at doses of 0.2, 2, 6, 20 nmol) or saline was injected into the MnR or into the pontine nucleus (Pn) of free-feeding rats. The animals were exposed to the elevated plus maze to analyse spatial-temporal and ethological variables. Subsequently, the ingestive and non-ingestive behaviors were recorded during 30 min and feeding and drinking behaviors were measured. Both in the elevated plus-maze and in the feeding chamber, all PHE doses injected into the MnR decreased the risk assessment frequency, an ethological parameter of anxiolytic-like effect. The spatial-temporal variables remained unchanged after PHE treatment. Feeding behavior was not affected by PHE into the MnR. The anxiety-like or ingestive behaviors were not affected by PHE treatment in the Pn, an area adjacent to the MnR. These data indicate that α1-adrenergic receptors within MnR participate in the control of anxiety-like behaviors. The absence of effects on feeding behavior after MnR α1-adrenergic activation could be due to an elevated α1-adrenergic tonus and its possible strong facilitatory influence on 5-HT neurons within MnR. Furthermore, the present results suggest that anxiety-like and feeding behaviors controled by MnR adrenergic circuits operate by independent neural pathways.
Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 1/farmacología , Ansiolíticos/farmacología , Ingestión de Alimentos/fisiología , Conducta Alimentaria/fisiología , Fenilefrina/farmacología , Núcleos del Rafe/fisiología , Animales , Relación Dosis-Respuesta a Droga , Conducta de Ingestión de Líquido , Ingestión de Alimentos/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Microinyecciones , Fenilefrina/administración & dosificación , Puente/efectos de los fármacos , Puente/fisiología , Núcleos del Rafe/efectos de los fármacos , Ratas , Ratas Wistar , Medición de Riesgo/métodosRESUMEN
Serotonergic neurons in the median raphe nucleus (MnR) are stimulated by alpha(1)-adrenergic agonists and inhibited by alpha(2) agonists. This study investigated the participation of MnR alpha(2)-adrenergic receptors in the control of anxiety-like behavior and feeding as an attempt to establish a functional association between these behaviors. The alpha(2)-adrenergic agonist clonidine (CLON) was injected into the MnR (0, 0.2, 2, 6, 20nmol), into the pontine nucleus (Pn) or into the mesencephalic reticular formation (mRt) (0.2, 20nmol) of free-feeding rats. The animals were exposed to the elevated plus-maze to evaluate spatial-temporal and ethological variables. Subsequently, the ingestive and non-ingestive behaviors were recorded during 30min and the quantity of food and water consumed were measured. The lowest dose of CLON injected into the MnR decreased the total risk assessment (TRA) frequency, an ethological parameter of anxiolytic-like effect, but did not change feeding behavior. The highest dose of CLON injected into the MnR increased the TRA frequency, an anxiogenic-like effect. Similar result was observed after CLON injected into the Pn and mRt at the highest dose. In addition, clonidine at the highest dose caused hyperphagy accompanied by a reduction in the latency to start eating and an increase in feeding frequency when injected into the MnR but not in the Pn or mRt. These data indicate that MnR alpha(2)-adrenergic receptors participate in the control of anxiety-like and feeding behaviors, probably decreasing the facilitatory influence on MnR serotonergic neurons. The present results suggest that these behaviors involve independent neural pathways.
Asunto(s)
Agonistas alfa-Adrenérgicos/farmacología , Trastornos de Ansiedad/fisiopatología , Clonidina/farmacología , Ingestión de Alimentos/efectos de los fármacos , Núcleos del Rafe/efectos de los fármacos , Análisis de Varianza , Animales , Trastornos de Ansiedad/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Núcleos del Rafe/fisiología , Ratas , Ratas WistarRESUMEN
This study investigated the effect of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 2.5 and 5.0 nmol/side) microinjected into the core and shell sub-regions of the accumbens (Acb) nucleus, on food intake and the level of anxiety in female rats. Bilateral microinjections of CNQX (5.0 nmol/side) into the Acb shell (AP, +1.08 to +2.04), but not into the Acb core, induced an anxiolytic-like effect in relation to rats microinjected with vehicle, since the animals exhibited low level of SAP in the feeding test. The anxiolytic-like effect induced by 5.0 nmol CNQX microinjection into the Acb shell may not be ascribed to changes in the motor activity of the animals, because the frequency of locomotion, rearing and grooming remained unchanged after the drug microinjection. However, neither Acb shell nor Acb core CNQX microinjections were able to change the animals food intake along 1h feeding behaviour evaluation. Food intake remained unchanged 24h after the drug microinjections either into the Acb shell or into the Acb core. The data suggest that AMPA receptor blockade in the Acb nucleus may differentially change the ingestive and defensive behaviours in female rats.
Asunto(s)
6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Ingestión de Alimentos/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Núcleo Accumbens/efectos de los fármacos , Receptores AMPA/antagonistas & inhibidores , 6-Ciano 7-nitroquinoxalina 2,3-diona/administración & dosificación , Análisis de Varianza , Animales , Ansiedad/fisiopatología , Ansiedad/psicología , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Relación Dosis-Respuesta a Droga , Ingestión de Alimentos/fisiología , Antagonistas de Aminoácidos Excitadores/administración & dosificación , Antagonistas de Aminoácidos Excitadores/farmacología , Conducta Exploratoria/efectos de los fármacos , Conducta Exploratoria/fisiología , Miedo/psicología , Femenino , Preferencias Alimentarias/efectos de los fármacos , Preferencias Alimentarias/fisiología , Aseo Animal/efectos de los fármacos , Aseo Animal/fisiología , Microinyecciones , Actividad Motora/fisiología , Núcleo Accumbens/metabolismo , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
This study investigated the effect of GABAA (muscimol, MUSC) and GABAB (baclofen, BACL) agonist receptors microinjected into medial accumbens shell on feeding and the level of fear in free-feeding rats submitted to the elevated plus-maze (EPM), an animal model of anxiety. Bilateral microinjections of either MUSC (128 pmol/0.2 microl/side) or BACL (128 and 256 pmol/0.2 microl/side) induced an anxiolytic-like effect since they decreased the occurrence of risk assessment, a defensive behaviour positively correlated with the animal anxiety level. Bilateral BACL microinjection (128 pmol), but not MUSC, also increased the head-dipping frequency over the open arms of the EPM, another representative behaviour of anxiety, but negatively correlated with it. In addition to anxiolysis, the present study also showed that the microinjection of MUSC and BACL agonists into rostral sites of the medial Acb shell (AP, +1.2 to +1.6) increased food intake significantly whereas drinking behaviour kept unchanged. Both doses of MUSC and BACL also decreased feeding latency. BACL but not MUSC dose-dependently increased food length. The data indicated a putative role of GABA receptors (especially GABAB) in the medial Acb shell for anxiety modulation in rats.
Asunto(s)
Ansiedad/tratamiento farmacológico , Baclofeno/administración & dosificación , Conducta Alimentaria/efectos de los fármacos , Agonistas del GABA/administración & dosificación , Muscimol/administración & dosificación , Núcleo Accumbens/efectos de los fármacos , Análisis de Varianza , Animales , Ansiedad/fisiopatología , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Aprendizaje por Laberinto/efectos de los fármacos , Microinyecciones/métodos , Ratas , Ratas Wistar , Tiempo de Reacción/efectos de los fármacosRESUMEN
Interictal spike detection is a time-consuming, low-efficiency task, but is important to epilepsy diagnosis. Automated systems reported to date usually have their practical efficacy compromised by elevated rates of false-positive detections per minute, which are caused mainly by the influence of artifacts (such as noise activity and ocular movements) and by the adoption of single or simple approaches. This work describes the development of a hybrid system for automatic detection of spikes in long-term electroencephalogram (EEG), named System for Automatic Detection of Epileptiform Events in EEG (SADE(3)), which uses wavelet transform, neural networks and artificial intelligence procedures to recognize epileptic and to reject non-epileptic activity. The system's pre-processing stage filters the EEG epochs with the Coiflet wavelet function, which showed the closest correlation to epileptogenic (EPG) activity, in opposition to some other wavelet functions that did not correlate with these events. In contrast to current attempts using continuous wavelet transform, we chose to work with fast wavelet transform to reduce processing time and data volume. Detail components at appropriate decomposition levels were used to accentuate spikes, sharp waves, high-frequency noise activity and ocular artifacts. These four detailed components were used to train four specialized neural networks, designed to detect and classify the EPG and non-EPG events. An expert module analyzes the networks' outputs, together with multichannel and context information and concludes the detection. The system was evaluated with 126,000 EEG epochs, obtained from seven different patients during long-term monitoring, under diverse behavior and mental states. More than 6,721 spikes and sharp waves were previously identified by three experienced human electroencephalographers. In these tests, the SADE(3) system simultaneously achieved 70.9% sensitivity, 99.9% specificity and a rate of 0.13 false-positives per minute, indicating its usefulness and low vulnerability to artifact influence. After tests, the SADE(3) system showed itself to be able to process bipolar cortical EEG records, from long-term monitoring, up to 32 channels, without any data preparation or event positioning. At the same time, SADE(3) revealed a high capacity to reject non-epileptic paroxysms, robustness in relation to a variety of spike morphologies, flexibility in adjustment of performance rates and the capacity to actually save time during EEG reading. Furthermore, it can be adapted to other applications for pattern recognition, with simple adjustments.
Asunto(s)
Epilepsia/diagnóstico , Procesamiento de Señales Asistido por Computador , Artefactos , Bases de Datos Factuales , Electroencefalografía/métodos , Humanos , Redes Neurales de la ComputaciónRESUMEN
The effect of the gradient of luminosity between the open and the enclosed arms (O/E(DeltaLux)) of the elevated plus maze (EPM), upon the level of fear/anxiety in rats submitted to the trial 1/trial 2 paradigm was investigated. Male Wistar rats were assigned to freely explore either of three EPM configuration, with the enclosed arm walls constructed with either translucent glass (O/E(DeltaLux)=11), opaque glass (O/E(DeltaLux)=96) or wood (O/E(DeltaLux)=141), for 2 consecutive days (trial 1/trial 2). Independently of the EPM configuration, rats exhibited increased fear during trial 2 relative to trial 1, thus indicating that the level of O/E(DeltaLux), at least in the range used here, is not a determinant variable for the establishment of increased anxiety induced by prior maze experience. The groups tested under 11 and 141 O/E(DeltaLux) were those who exhibited the low and higher level of open arm avoidance, respectively. There was also an increased open arms avoidance over trial 1 in rats tested under 11 and 96 O/E(DeltaLux), only. These results suggest that the enclosed arm preference of rats during trial 1 EPM procedure may be changed by the level of O/E(DeltaLux) of the test. The present results are discussed with respect to the controversy regarding the role of luminosity on EPM performance.