Low doses of ethanol disrupt sensory responses of brain noradrenergic neurones

Abstract

Ethanol is a widely abused drug which has many behavioural and psychological effects¹. In spite of considerable research^1–4, the brain mechanisms responsible for these effects are unknown. Previously, it has been proposed that noradrenaline (NA)-containing locus coeruleus (LC) neurones, which project throughout the brain^5,6, mediate the effects of many abused as well as clinically effective psychoactive agents^7,8. Recent studies^9–11 have shown that in freely behaving, undrugged animals, NA-containing LC (NA-LC) neurones exhibit marked, short-latency responses to sensory stimuli of many modalities, perhaps serving to bias brain and behavioural activities towards adaptive responses to phasic, unexpected environmental events. We have now examined the effects of ethanol on these sensory responses of NA-LC neurones. In the present study, anaesthetized animals were used to minimize fluctuations in arousal, providing a more stable baseline for assessing pharmacological effects. A class of NA-LC sensory responses which mimic those observed in unanaesthetized animals was studied. In addition, using antidromic stimulation, we investigated the effects of ethanol on the soma excitability, axonal conduction velocity, and strength of recurrent collateral inhibition of these neurones. We now report that low intoxicating doses of ethanol substantially reduce the magnitude and temporal reliability of sensory-evoked responses in NA-LC neurones, perhaps due in part to enhanced feedback inhibition of these cells.