RESUMO
Cerebellar participation in timing and sensory-motor sequences has been supported by several experimental and clinical studies. A relevant role of the cerebellum in timing of conditioned responses in the range of milliseconds has been demonstrated, but less is known regarding the role of the cerebellum in supra-second timing of operant responses. A dissociated role of the cerebellum and striatum in timing in the millisecond and second range had been reported, respectively. The climbing fibre-Purkinje cell synapse is crucial in timing models; thus, the aberrant connection between these cellular elements is a suitable model for evaluating the contribution of the cerebellum in timing in the supra-second range. The aberrant connection between climbing fibres and Purkinje cells was induced by administration of the antagonist of NMDA receptors MK-801 to Sprague-Dawley rats at postnatal days 7-14. The timing of an operant response with two fixed intervals (5 and 8 s) and egocentric sequential learning was evaluated in 60-day-old adult rats. The aberrant connections caused a reduced accuracy in the timing of the instrumental response that was more evident in the 8-s interval and a reduced number of successive correct responses (responses emitted in the correct second without any other response between them) in the 8-s interval. In addition, an inability to incorporate new information in a sequence previously learned in egocentric-based sequence learning was apparent in rats with aberrant CF-PC synapses. These results support a relevant role for the cerebellum in the fine-tuning of the timing of operant responses in the supra-second range.
Assuntos
Comportamento Animal/fisiologia , Cerebelo/citologia , Condicionamento Operante/fisiologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Aprendizagem/fisiologia , Células de Purkinje/fisiologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Aprendizagem Seriada/fisiologia , Sinapses/fisiologia , Percepção do Tempo/fisiologia , Animais , Axônios/efeitos dos fármacos , Axônios/fisiologia , Comportamento Animal/efeitos dos fármacos , Cerebelo/efeitos dos fármacos , Condicionamento Operante/efeitos dos fármacos , Maleato de Dizocilpina/farmacologia , Aprendizagem/efeitos dos fármacos , Masculino , Núcleo Olivar/fisiologia , Células de Purkinje/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Aprendizagem Seriada/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Percepção do Tempo/efeitos dos fármacosRESUMO
The amnestic effects of flunitrazepam (2 mg intravenously) were studied in normal volunteers with emphasis on their relationship to sleep and their reversal by two specific benzodiazepine receptor antagonists (Ro 15-1788 and Ro 15-3505). The test battery was based on available clinical tests to assess various aspects of encoding and recall. The results suggest that flunitrazepam impairs acquisition of new information by interfering with encoding, and that these effects are clearly independent of sleep. Flunitrazepam effects on memory were fully reversed by both antagonists, as were the subjective and objective signs of sedation. This speaks against the hypothesis of different receptors for sedative and amnestic effects. Ro 15-3505 had shorter lasting effects than Ro 15-1788 and interfered with some tests; this is discussed in relation to its inverse agonistic effects.