Local application of bicuculline potentiates NMDA‐receptor‐mediated sensory responses of brain noradrenergic neurons

Direct application of bicuculline methiodide (BIC) to noradrenergic locus coeruleus (LC) neurons potently enhanced their sensory responsiveness. This increased responsiveness was due to the long‐lasting expression of a new, N‐methyl‐D‐aspartate (NMDA) receptor‐mediated component of the synaptic response. This enhancement only occurred when a high stimulus intensity was used to induce the sensory response. A similar increase in responsiveness was observed with stimulation of the nucleus paragigantocellularis (PGi), one of the major direct afferents to LC. This action of BIC was neither mimicked by picrotoxin, penicillin, or the GABA‐B antagonist, 2‐hydroxysaclofen, nor by agents that directly depolarize LC neurons. In addition, the inverse agoinst of the benzodiazepine receptor, methyl‐6,7‐dimethoxy‐4‐ethyl‐β‐carboline‐3‐carboxylate (DMCM), did not mimic this effect of BIC. The BIC‐potentiated response component was eliminated by direct application of the neurotransmitter γ‐aminobutyric acid (GABA). These results indicate that BIC, acting at a possibly novel site, unmasks NMDA receptors that can be activated by sensory stimuli. This may reflect a mechanism whereby interactions between two major neurotransmitter systems, excitatory amino acids (EAAs) and GABA, potently modulate signal transmission in the brain.