Distribution of alpha 2 agonist binding sites in the rat and human central nervous system: analysis of some functional, anatomic correlates of the pharmacologic effects of clonidine and related adrenergic agents

Author(s): Unnerstall JR, Kopajtic TA, Kuhar MJ


Using [3H]para-aminoclonidine, alpha 2 adrenergic binding sites have been mapped in the rat and human CNS using in vitro labeling autoradiographic techniques. In both the rat and human thoracic spinal cord, high densities of alpha 2 binding sites were associated with the substantia gelatinosa and the intermediolateral cell column. In the rat medulla, high binding site density was observed in the medial nucleus of the solitary tract, dorsal motor nucleus of the vagus, raphe pallidus and the substantia gelatinosa of the trigeminal nucleus, while lower levels of specific binding were found in the lateral and ventrolateral medulla. In the human, a similar distribution was observed. However, significantly lower levels of specific binding were seen in the medial nts as opposed to the dmv. In the rat, high levels of specific binding were seen at pontine and midbrain levels in the locus coeruleus, parabrachial nucleus and periaqueductal gray. In the forebrain, several hypothalmic and limbic regions, including the paraventricular and arcuate nuclei of the hypothalamus, the central, medial and basal nuclei of the amygdala, lateral septum and bed nucleus of the stria terminalis and pyriform, entorhinal and insular cortex were labeled. Each of these regions are involved in either modulating autonomic functions directly or integrating somatosensory and/or affective function with autonomic mechanisms. Further, these regions are interrelated by reciprocal connections, and neurons that utilize noradrenaline or adrenaline as their neurotransmitter form a vital part of these connections. Thus, these functional, anatomical and neurochemical correlates of the alpha 2 binding site distribution establish a neurological basis for the complex pharmacological effects of centrally acting alpha 2 agonists.

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