Enrique Burunat

Conditioning of the early behavioral response to apomorphine in the rotational model of Parkinson's disease

The rotational model of Parkinsons disease has been widely used to investigate the action of dopamine agonists. This animal model involves the production of a unilateral nigrostriatal lesion in rats. The lesion is produced with 6-hydroxydopamine which causes dopamine depletion and subsequent supersensitivity of striatal receptors. Thus, administration of drugs which are therapeutically effective in Parkinsons disease, elicits circling behavior contralateral to the lesioned side. The origin of the paradoxical response and the undrugged rotations observed after saline injections in apomorphine pretreated rats has not been explained. We report here that the undrugged response can be associated with the early rotational response elicited by the drug. Furthermore, we show the effect of inhibitory conditioning on this early response. Our results suggest that pharmacological conditioning plays a significant role in the modification of the therapeutic effectiveness of CNS-active drugs after extended treatments.

Undrugged rotational response in nigro-striatal system-lesioned rats is related to the previous early response to apomorphine when repeatedly administered

Development and time-course characteristics of undrugged rotational response weeks or months after repeated apomorphine administration in 6-hydroxydopamine-lesioned rats were explored. In one series of experiments, all groups received several drug doses two-three weeks post-lesion and remained undrugged at different intervals from the last drug injection. Weeks or months later, they were injected with saline in the same environment where they previously had received apomorphine. In this way we studied acquisition, time-course and extinction of the rotational response after saline. Furthermore, we related this undrugged response which does not fully develop until two weeks after treatment, and which previously had not been related to a specific parameter of the rotational response to the drug, to a critical point of the time-course response to the drug, i.e., the early rotational response in the first minute after injection. This early response is a learning phenomenon based on the environmental cues where drug has been repeatedly administered. Finally, we state the concept of pharmacological conditioning using this animal model of Parkinsons disease, in agreement with our own results and the previous results of Silverman and Ho (1981).

El desarrollo del sustrato neurobiológico de la motivación y emoción en la adolescencia: ¿un nuevo período crítico?

Resumen Evidencias recientes sugieren la posible relación de estructuras cerebrales concretas con algunas características del procesamiento cognitivo en la adolescencia. La maduración de porciones de los lóbulos frontales y su relación con circuitos y estructuras cerebrales como, por ejemplo, el sistema límbico, asociado a la experiencia y expresión emocional, o los ganglios basales, a su vez implicados en la regulación de la actividad motora, podrían ser los responsables de la impulsividad, el descontrol emocional, la proclividad a la aparición de conductas adictivas, los desórdenes afectivos, la esquizofrenia, la personalidad antisocial, etc., que pueden presentarse en esta etapa del desarrollo. Diferencias sutiles neuroanatómicas y funcionales entre ambos sexos podrían estar implicadas en la mayor predisposición masculina a las conductas de riesgo. Dado el papel fundamental de la experiencia en la maduración cerebral programada desde el genotipo del individuo, especialmente en momentos específicos del desarrollo cerebral—los conocidos como “períodos críticos del desarrollo”—parece necesario, tanto avanzar en el conocimiento de las bases neurobiológicas del desarrollo cognitivo en la adolescencia, como precisar “el modo” en el que la experiencia afecta al desarrollo de estas estructuras y circuitos, especialmente en aquellos implicados en la adquisición de normas éticas de conducta.

Conditioned response to apomorphine in nigro-striatal system-lesioned rats: The origin of undrugged rotational response

Development and time-course characteristics of Early rotational response (ER) to apomorphine in 6-hydroxydopamine-lesioned rats is explored. We show here how this ER can be considered a conditioned response that arises when the drug is repeatedly administered, according to a classical conditioning paradigm. In this way, the ER to apomorphine can be considered a non-pharmacological, conditioned, placebo response, the drug action being the unconditioned stimulus (UCS). In our model, the undrugged rotational response elicited by saline injections two weeks after drug treatment can be considered as the conditioned response (CR) to the conditioned stimulus, the CS being the environment associated with the drug treatment. This CR had not previously been identified during the drug treatment. Thus, we studied the acquisition of the ER, nonexistent after the first injection of apomorphine. Furthermore, we distinguish between this ER and the later, strictly pharmacological rotational response (LR) to apomorphine. Finally, we related this ER to the undrugged, paradoxical response to saline. In conclusion, we demonstrate the paradigm of pharmacological conditioning using this animal model of Parkinsons disease, supported by our own results and those of Silverman and Ho (1981).

A low cost fMRI-compatible tracking system using the Nintendo Wii remote

It is sometimes necessary during functional magnetic resonance imaging (fMRI) experiments to capture different movements made by the subjects, e.g. to enable them to control an item or to analyze its kinematics. The aim of this work is to present an inexpensive hand tracking system suitable for use in a high field MRI environment. It works by introducing only one light-emitting diode (LED) in the magnet room, and by receiving its signal with a Nintendo Wii remote (the primary controller for the Nintendo Wii console) placed outside in the control room. Thus, it is possible to take high spatial and temporal resolution registers of a moving point that, in this case, is held by the hand. We tested it using a ball and racket virtual game inside a 3 Tesla MRI scanner to demonstrate the usefulness of the system. The results show the involvement of a number of areas (mainly occipital and frontal, but also parietal and temporal) when subjects are trying to stop an object that is approaching from a first person perspective, matching previous studies performed with related visuomotor tasks. The system presented here is easy to implement, easy to operate and does not produce important head movements or artifacts in the acquired images. Given its low cost and ready availability, the method described here is ideal for use in basic and clinical fMRI research to track one or more moving points that can correspond to limbs, fingers or any other object whose position needs to be known.