Norepinephrine has been implicated in a number of physiological, behavioral, and cellular modulatory processes in the brain, and many of these modulatory effects are attributable to alpha1 adrenergic receptors. At least three alpha1 receptor subtypes have been identified by molecular criteria, designated alpha1A, alpha1B, and beta1D. The distributions of alpha1B and alpha1D receptor mRNA expression in rat brain have been described previously, but the cDNA for the rat alpha1A receptor has only recently been cloned and characterized. In the present study, we used a radiolabelled riboprobe derived from the rat alpha1A receptor cDNA to describe the distribution of alpha1A message expression in the rat brain. The highest levels of alpha1A adrenergic receptor mRNA expression were seen in the olfactory bulb, tenia tectae, horizontal diagonal band/magnocellular preoptic area, zona incerta, ventromedial hypothalamus, lateral mammillary nuclei, ventral dentate gyrus, piriform cortex, medial and cortical amygdala, magnocellular red nuclei, pontine nuclei, superior and lateral vestibular nuclei, brainstem reticular nuclei, and several cranial nerve motor nuclei. Dual in situ hybridization combining a radioactive riboprobe for choline acetyltransferase mRNA with a digoxigenin-labeled alpha1A riboprobe in the fifth and seventh cranial nerve motor nuclei showed that the alpha1A mRNA is expressed in cholinergic motor neurons. Prominent alpha1A hybridization signal was also seen in the neocortex, claustrum, lateral amygdala, ventral cochlear nucleus, raphe magnus, and in the ventral horn of thoracic spinal cord. This overall pattern of expression, considered in comparison with that previously described for the other alpha1 adrenergic receptor subtypes, may shed light on the different roles of the alpha1 receptors in mediating the neuromodulatory effects of norepinephrine in processes such as arousal, neuroendocrine control, sensorimotor regulation, and the stress response.
