Effects of systemically and locally applied cocaine on cerebrocortical neuron responsiveness to afferent synaptic inputs and glutamate.

Abstract The goal of the present study was to determine the effects of systemically or locally applied cocaine on rat somatosensory cortical neuron responsiveness to afferent synaptic inputs or putative transmitter application and to compare these results with previously observed actions of endogenous cortical monoamines on the same parameters of neuronal function. Individual cells in rat cortex were activated by stimulation of thalamocortical afferents or local iontophoretic application of glutamate. Extracellularly recorded responses to these stimuli were monitored before and after parenteral or microiontophoretic administration of cocaine. The results indicate that while high doses ( > 2.0mg/kg i.p.) of the drug can suppress both evoked and spontaneous activity of cortical neurons, low doses (0.5 mg/kg i.p.) can selectively enhance stimulus-evoked discharge. These facilitating effects can also be observed during iontophoretic application of cocaine directly onto recorded cells, thus suggesting that at least a component of the drug's influence on neuronal responsiveness is mediated by local actions at synapses within the cortex. Of the 3 major endogenous cortical monoamines whose synaptic reuptake is influenced by cocaine, the actions reported here mimic those described previously for norepinephrine but not those of dopamine or serotonin. As such these findings suggest that cocaine may enhance the responsiveness of sensory cortical neurons to afferent synaptic inputs via its ability to activate noradrenergic modulatory mechanisms within the cerebrocortical circuitry.