RESUMEN
The prefrontal cortex (PFC) of the rat supports cognitive flexibility, the ability to spontaneously adapt goal-directed behavior in response to radically changing situational demands. We have shown previously that transient inactivation of the rat medial PFC (mPFC) impairs initial reversal learning in a spatial 2-lever discrimination task. Given the importance of dopamine (DA) for PFC function, we studied DA (and noradrenaline [NA]) efflux in the mPFC during reversal learning. We observed a higher and more extended increase in DA efflux in rats performing the first reversal compared with controls performing the previously acquired discrimination. The results of an additional experiment suggest that such a difference between the reversal- and control-induced DA increases was absent during a third reversal. During the extinction session, DA efflux did not increase from basal levels. Increases in NA efflux were less than in DA and did not differ between control and any condition. We conclude that prefrontal DA activity is increased during execution of instrumental discrimination tasks and that this increase is amplified during the acquisition of a first, but not of later reversals. These data corroborate our previous findings and indicate that DA is critically involved in this form of cognitive flexibility.
Asunto(s)
Dopamina/metabolismo , Extinción Psicológica/fisiología , Norepinefrina/metabolismo , Corteza Prefrontal/metabolismo , Aprendizaje Inverso/fisiología , Animales , Conducta Animal/fisiología , Cognición/fisiología , Objetivos , Masculino , Microdiálisis , Corteza Prefrontal/fisiología , Ratas , Ratas WistarRESUMEN
We trained rats to learn that an auditory stimulus predicted delivery of reward pellets in the Skinner box. After 2 d of training, we measured changes in efflux of noradrenaline (NA) and dopamine (DA) in the medial prefrontal cortex using microdialysis on the third day. Animals were subjected to a normal rewarded session and an extinction session, in which the auditory stimulus was presented alone. In the rewarded session, both NA and DA efflux were increased, but in extinction, only NA was activated. The data suggest that NA has a role in the reaction to reward-predicting stimuli, which complements that of DA.
Asunto(s)
Conducta Apetitiva/fisiología , Condicionamiento Clásico/fisiología , Dopamina/metabolismo , Norepinefrina/metabolismo , Corteza Prefrontal/metabolismo , Estimulación Acústica , Animales , Conducta Animal/fisiología , Extinción Psicológica/fisiología , Masculino , Microdiálisis , Ratas , Ratas Wistar , Tiempo de Reacción/fisiología , RecompensaRESUMEN
Previous experiments have shown that infusions of ibotenic acid in the nucleus basalis magnocellularis (NBM) induce a strong impairment in spatial navigation for a hidden platform in the Morris water maze. This effect was initially attributed to a cholinergic deficit, but later studies showed that performance level did not correlate with the degree of cholinergic denervation. Therefore, this impairment is due to a combined cholinergic and non-cholinergic deficit. However, it is not clear in which particular processes the NBM is involved. In this study we have evaluated the origin of behavioural impairment in spatial navigation in the water maze after an ibotenic acid-induced lesion of NBM. In the first experiment, Wistar rats were trained preoperatively in an allocentric navigation task. Postoperatively, they were tested in the same task. All lesioned animals showed a performance level similar to controls. Lesions did not impede the acquisition of new positions in the water maze, nor did affect the ability of animals to remember new platform positions after an intertrial interval of 20s, even if animals had received only allocentric experience with the platform position, or allocentric and path integration information concurrently. Lesions also failed to affect the ability to locate a hidden platform in a new environment. However, hippocampal infusions of scopolamine (5 microg) produced a severe impairment in NBM-damaged animals, without impairing performance of controls. In the second experiment Wistar rats with the same lesion were first trained in a visual-guided task in the water maze, and subsequently evaluated in the spatial task. In both tasks lesioned animals were not different from controls. These results suggest that the NBM played an important role during acquisition phases but not in the execution of spatial navigation. Moreover, the excessive emotional response displayed by lesioned animals is postulated as a relevant cause for the impairment observed in spatial navigation after NBM damage.
Asunto(s)
Núcleo Basal de Meynert/patología , Aprendizaje por Laberinto/fisiología , Conducta Espacial/fisiología , Animales , Reacción de Prevención/efectos de los fármacos , Reacción de Prevención/fisiología , Núcleo Basal de Meynert/efectos de los fármacos , Señales (Psicología) , Aprendizaje Discriminativo/efectos de los fármacos , Aprendizaje Discriminativo/fisiología , Agonistas de Aminoácidos Excitadores/toxicidad , Hipocampo/efectos de los fármacos , Hipocampo/fisiología , Ácido Iboténico/toxicidad , Masculino , Antagonistas Muscarínicos/farmacología , Ratas , Ratas Wistar , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiología , Aprendizaje Inverso/efectos de los fármacos , Aprendizaje Inverso/fisiología , Escopolamina/farmacologíaRESUMEN
We tested the hypothesis that inhibition of NMDA-receptors in rats would lead to a selective impairment of reversal learning in a serial reversal task in the Skinner box. Low doses of MK-801 (0.025 and 0.05 mg/kg) did not affect acquisition of the two-lever discrimination, but impaired performance during the first reversal more than during the third reversal. Similar effects were observed during the series of extinction sessions. The high dose (0.1 mg/kg) completely inhibited reversal and extinction learning, as the rats perseverated in pressing the previously rewarded lever(s). We conclude that NMDA receptor blockade leads to a selective impairment in cognitive flexibility, and shows some similarity to transient inactivation of the medial prefrontal cortex in this respect.
Asunto(s)
Maleato de Dizocilpina/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Aprendizaje Inverso/efectos de los fármacos , Animales , Masculino , Ratas , Ratas Wistar , Receptores de N-Metil-D-Aspartato/fisiología , Aprendizaje Inverso/fisiologíaRESUMEN
In this study we have examined the involvement of the prefrontal cortex (PFC) along with the Nucleus basalis magnocellularis (NBM) in two types of spatial navigation tasks. We evaluated the effects of excitotoxic (ibotenate-induced) lesions of the NBM in an allocentric and an egocentric task in the Morris water maze, using sham operations for a comparison. In both cases we also assessed the effects of local cholinergic receptor blockade in the PFC by infusing the muscarinic receptor antagonist scopolamine (4 or 20 microg). Anatomically, the results obtained showed that this lesion produced a profound loss of acetylcholinesterase (AChE) positive cells in the NBM, and a loss of AChE positive fibres in most of the neocortex, but hardly in the medial PFC. Behaviourally, such lesions led to a severe impairment in the allocentric task. Intraprefrontal infusions of scopolamine led to a short-lasting impairment in task performance when the high dose was used. In the second experiment, using the same surgical manipulations, we examined the performance in the egocentric task. Like in the allocentric task animals with NBM lesions were also impaired, but with continued training they acquired a level of performance similar to the sham-operated ones. This time, infusions of scopolamine in the medial PFC led to a severe disruption of performance in both groups of animals. We conclude that acetylcholine in the medial PFC is important for egocentric but not allocentric spatial memory, whereas the NBM is involved in the learning of both tasks, be it to a different degree.