RESUMEN
The goal of the present study was to investigate the effects of intravenous cocaine administration on cerebellar Purkinje cell firing. Extracellular neuron activity was recorded and cells were locally excited with spaced microiontophoretic pulses of glutamate. Glutamate-evoked and spontaneous discharges were compared before and immediately following cocaine administration. Cocaine injections (1. 0 and 0.25 mg/kg, i.v.) induced a reversible suppression of both spontaneous activity and glutamate-evoked excitation. Procaine was ineffective in producing similar actions. Cocaine only inhibited glutamate-induced excitation in animals pre-treated with reserpine (5 mg/kg, i.p.). Propranolol injections (10 mg/kg, i.p.) were ineffective in blocking cocaine-induced inhibitions. Yohimbine (5 mg/kg, i.p.) pre-treatment abolished cocaine-induced suppressions of either spontaneous or glutamate-evoked excitation. Therefore, cocaine administration decreases Purkinje cell spontaneous and glutamate-evoked discharges by a mechanism involving alpha(2)-adrenoceptor activation. It is suggested that by changing the normal function of the cerebellum cocaine can produce drug-related alterations in overt behavior and cognition.
Asunto(s)
Potenciales de Acción/efectos de los fármacos , Cocaína/farmacología , Inhibidores de Captación de Dopamina/farmacología , Ácido Glutámico/farmacología , Células de Purkinje/efectos de los fármacos , Receptores Adrenérgicos alfa 2/efectos de los fármacos , Potenciales de Acción/fisiología , Inhibidores de Captación Adrenérgica/farmacología , Antagonistas Adrenérgicos alfa/farmacología , Antagonistas Adrenérgicos beta/farmacología , Anestésicos Locales/farmacología , Animales , Cerebelo/efectos de los fármacos , Cerebelo/fisiología , Masculino , Procaína/farmacología , Propranolol/farmacología , Células de Purkinje/fisiología , Ratas , Ratas Sprague-Dawley , Receptores Adrenérgicos alfa 2/fisiología , Reserpina/farmacología , Yohimbina/farmacologíaRESUMEN
Ever since the initial demonstration of a widespread distribution of noradrenergic fibers to functionally diverse regions of the mammalian forebrain, there has been considerable interest in determining the electrophysiological effects of norepinephrine (NE) on individual neurons within these target areas. While early studies showed that NE could directly inhibit cell firing via increased intracellular levels of cyclic AMP, more recent work has revealed a spectrum of noradrenergic actions, which are more accurately characterized as neuromodulatory. More specifically, numerous experimental conditions have been described where NE at levels subthreshold for producing direct depressant effects on spontaneous firing can facilitate neuronal responses to both excitatory and inhibitory synaptic stimuli. The goal of this report is to review recent evidence which suggests that the various modulatory actions of NE on central neurons result from the activation of different adrenoceptor-linked second messenger systems. In particular, we have focused on the candidate signal transduction mechanisms that may underlie NE's ability to augment cerebellar and cortical neuronal responsiveness to GABAergic synaptic inputs. The consequences of such NE-induced changes in synaptic efficacy are considered not only with respect to their influences on feature extraction properties of individual sensory cortical neurons but also with regard to the potential impact such actions would have on the signal processing capabilities of a network of noradrenergically innervated cortical cells.