The Role of Alpha 1-adrenoceptor-mediated Collateral Excitation in the Regulation of the Electrical Activity of Locus Coeruleus Neurons

The physiological role of two types of autoreceptors, alpha 1- and alpha 2-adrenoceptors, located on the somadendritic membranes of locus coeruleus neurons, was studied in the developing and adult rat brain. Animals from birth to adulthood were anesthetized with urethan, and single-unit activity was recorded extracellularly in the locus coeruleus. The spontaneous firing of most locus coeruleus neurons was inhibited by iontophoretic application of noradrenaline at a high concentration, while noradrenaline at a low concentration frequently caused excitation of the neurons, predominantly in the developing brain. A similar excitation was also produced by iontophoretic application of the alpha 1-agonist phenylephrine. These excitations were antagonized by the alpha 1-antagonist, 2-beta [4-hydroxyphenylethylaminomethyl]-tetralone, while this antagonist had little effect on glutamate-induced excitation. The noradrenaline- and phenylephrine-induced excitation occurred more frequently in the neurons having little or no spontaneous activity. Electrical stimulation of the dorsal noradrenergic bundle arising in the locus coeruleus produced both inhibition and excitation. The excitatory responses were manifest primarily in early developmental stages, and occurred predominantly when the neurons had little or no spontaneous activity. When the neurons began firing at relatively high rates, the effects of dorsal noradrenergic bundle stimulation became principally inhibitory. Since the excitation evoked by dorsal noradrenergic bundle of stimulation was blocked by the alpha 1-antagonist, the excitation was thought to result from activation of alpha 1-adrenoceptors by noradrenaline released from the terminals of recurrent axon collaterals of locus coeruleus neurons themselves.(ABSTRACT TRUNCATED AT 250 WORDS)