Neurophysiological consequences of presynaptic receptor activation: changes in noradrenergic terminal excitability.

Experiments were carried out to explore the view that activation of presynaptic receptors on the terminals of noradrenergic neurons is accompanied by alterations in their excitability to direct electrical stimulation. Antidromic action potentials evoked from frontal cortex of urethane anesthetized rats were recorded extracellularly from nucleus locus coeruleus. The threshold current necessary to evoke antidromic action potentials varied as a result of infusion of adrenergic agonists and antagonists into frontal cortex within 50 micrometer of the stimulating electrode. Local infusion of the alpha-adrenergic agonist clonidine produced a marked decrease in terminal excitability, while the alpha-antagonist phentolamine produced an increase in terminal excitability and was shown to reverse the effect of the agonist. Infusion of the beta-adrenergic agonist isoproterenol was without effect, although the beta-antagonist propranolol resulted in a decrease in terminal excitability. Infusions of potassium increased excitability of locus coeruleus terminals. Terminal excitability was seen to vary inversely with the rate of spontaneous or high frequency stimulation-induced firing of locus coeruleus neurons. From these observations, it may be inferred that activation or blockade of alpha-adrenergic presynaptic receptors results in changes in polarization and/or conductance of the noradrenergic synaptic endings. These results are discussed with respect to phenomena associated with the possible presynaptic regulation of neurotransmitter release.