RESUMEN
The nucleus accumbens, as the main input structure of the ventral basal ganglia loop, is described as a limbic-motor interface. Dopamine input to nucleus accumbens modulates processing of concurrent glutamate input from limbic structures carrying motor and motivational information. There is evidence that these dopamine/glutamate interactions are fundamentally involved in response selection processes. However, the pedunculopontine tegmental nucleus (PPTg) in the brainstem is connected with limbic structures as well as dopaminergic midbrain areas, which also project to the nucleus accumbens. Furthermore, behavioral studies implicate the PPTg in complex, motivated behavior. Thus, the PPTg might be involved in motivated behavior by influencing response selection processes in the nucleus accumbens. In this study we used in vivo microdialysis in freely moving rats in order to inhibit (100, 200, 300 and 400 microm baclofen) or stimulate [5, 12.5, 25 or 50 micromalpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)] the PPTg in animals that are performing an operant discrimination task for food reward. The behavioral consequences were correlated with dopamine and glutamate levels in nucleus accumbens and PPTg, respectively. PPTg inhibition by local GABAB receptors impaired the response rate and accuracy of performance in the operant discrimination task. PPTg stimulation by local AMPA receptors exclusively impaired the response rate. Both treatments blocked the performance-driven dopamine signal in nucleus accumbens, whereas glutamate in PPTg was enhanced after AMPA administration only. The data indicate that the PPTg functionally participates in a network of subcortical and cortical structures, which is responsible for the execution of motivated behavior and response selection processes.
Asunto(s)
Condicionamiento Operante/fisiología , Discriminación en Psicología/fisiología , Dopamina/metabolismo , Ácido Glutámico/metabolismo , Mesencéfalo/fisiología , Receptores de Glutamato/fisiología , Ácido gamma-Aminobutírico/metabolismo , Análisis de Varianza , Animales , Baclofeno/farmacología , Conducta Animal , Química Encefálica , Condicionamiento Operante/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Masculino , Microdiálisis/métodos , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/fisiología , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico/farmacologíaRESUMEN
Energy intake and expenditure is a highly conserved and well-controlled system with a bias toward energy intake. In times of abundant food supply, individuals tend to overeat and in consequence to increase body weight, sometimes to the point of clinical obesity. Obesity is a disease that is not only characterized by enormous body weight but also by rising morbidity for diabetes type II and cardiovascular complications. To better understand the critical factors contributing to obesity we performed the present study in which the effects of energy expenditure and energy intake were examined with respect to body weight, localization of fat and insulin resistance in normal Wistar rats. It was found that a diet rich in fat and carbohydrates similar to "fast food" (cafeteria diet) has pronounced implication in the development of obesity, leading to significant body weight gain, fat deposition and also insulin resistance. Furthermore, an irregularly presented cafeteria diet (yoyo diet) has similar effects on body weight and fat deposition. However, these rats were not resistant to insulin, but showed an increased insulin secretion in response to glucose. When rats were fed with a specified high fat/carbohydrate diet (10% fat, 56.7% carbohydrate) ad lib or at the beginning of their activity phase they were able to detect the energy content of the food and compensate this by a lower intake. They, however, failed to compensate when food was given in the resting phase and gained more body weight as controls. Exercise, even of short duration, was able to keep rats on lower body weight and reduced fat deposition. Thus, inappropriate food intake with different levels of energy content is able to induce obesity in normal rats with additional metabolic changes that can be also observed in humans.
Asunto(s)
Peso Corporal/fisiología , Ingestión de Alimentos/fisiología , Alimentos , Resistencia a la Insulina/fisiología , Condicionamiento Físico Animal/fisiología , Esfuerzo Físico/fisiología , Tejido Adiposo/patología , Animales , Glucemia/metabolismo , Restricción Calórica , Dieta , Carbohidratos de la Dieta/farmacología , Grasas de la Dieta/farmacología , Ingestión de Líquidos , Prueba de Tolerancia a la Glucosa , Vivienda para Animales , Insulina/sangre , Iluminación , Masculino , Obesidad/patología , Ratas , Ratas Wistar , Aislamiento SocialRESUMEN
The pedunculopontine tegmental nucleus (PPTg) as part of the mesencephalic locomotor region is discussed to be involved in motor activity. In this study, we examined whether the PPTg plays a role in exploratory behaviour. Therefore, we compared non-habituated motor behaviour of PPTg lesioned rats with sham lesioned rats under spontaneous, dizocilpine (MK-801) (0.1 and 0.16 mg/kg) and dl-amphetamine (1 and 2 mg/kg) conditions. In order to analyse exploratory behaviour only, session-times were limited to 5 min after placing the rats in an open field. The exploratory motor activity was compared to the motor activity obtained in rats habituated to the environment. PPTg lesions had no effect on spontaneous exploratory behaviour, but it intensified the enhanced motor activity induced by MK-801. However, PPTg lesions blocked the enhanced exploratory behaviour, i.e. horizontal activity, rearing and centre activity induced by amphetamine. These data indicate that the PPTg is involved in behaviour driven by the dopaminergic and glutamatergic systems, when the animals are in a particular motivational state, e.g. a state that increases motor activity for itself, like exploration. This is underlined by the finding that animals exploring their environment show a higher motor activity even after multiple sessions, than animals familiar to the environment.
Asunto(s)
Conducta Exploratoria/efectos de los fármacos , Ácido Iboténico/toxicidad , Actividad Motora/efectos de los fármacos , Tegmento Mesencefálico/fisiopatología , Anfetamina/farmacología , Análisis de Varianza , Animales , Conducta Animal , Estimulantes del Sistema Nervioso Central/farmacología , Maleato de Dizocilpina/farmacología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Antagonistas de Aminoácidos Excitadores , Conducta Exploratoria/fisiología , Habituación Psicofisiológica/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Tegmento Mesencefálico/patologíaRESUMEN
The pedunculopontine tegmental nucleus (PPTg) has an important anatomical position connecting basal ganglia and limbic systems with motor execution structures in the pons and spinal cord. It receives glutamatergic and GABAergic input and has additional reciprocal connections with mesencephalic dopaminergic neurons, suggesting that the PPTg plays a key role in frontostriatal information processing. In vivo microdialysis in freely moving rats, in combination with behavioral analysis, was used in this study to investigate whether the dopaminergic input can be modulated at the level of the PPTg via N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) or GABA(B) receptors. Stimulation of the GABA(B) receptor decreased dopamine release in the PPTg while that of the AMPA and NMDA receptors increased it. A time-related comparison of the effects of NMDA (0.75 and 1 mM) and AMPA (50 and 25 microM) revealed a more long-lasting effect after AMPA stimulation than after NMDA. However, only the infusion of the GABA(B) receptor agonist baclofen (100 and 200 microM) stimulated stereotyped behavior (e.g. sniffing, digging or head movements) and contralateral circling. This study clearly demonstrates that GABAergic as well as glutamatergic terminals in the PPTg are critically involved in the modulation of the dopamine system. Moreover, a decrease in PPTg dopamine via GABA(B) receptor stimulation seems to be behaviorally relevant.