Alpha-adrenoceptor function in acute paranoid schizophrenia.

Although the therapeutie efTect of neuroleptie medication has been attributed largely to dopamine receptor blockade, noradrenergic transmission is also inhibited by administration of these drugs and should not be overlooked. In recent years extensive studies of the central noradrenergie metabolism led to the hypothesis of noradrenergie dysfunction in schizophrenia. Both norepinephrine and its metabolite MHPG have been found to be increased in the nucleus accumbens, mesencephalon, and Iimbie regions of the brain of paranoid schizophrenics (Farley et aI. 1978). In addition, investigations of noradrenergie receptor function have been conducted. Alpha-adrenergic receptors are found in hypothalamie, Iimbie, and cortical structures, whereas beta-receptors are found in cortical projections from the locus coeruleus. Although beta-adrenoceptor function has not yet been examined, alpha-adrenoceptor function on platelets, as a model for alpha-adrenergie function throughhout the body, has been studied in schizophrenie patients. Elevated alphaadrenoceptor numbers have been found in these patients associated with a deficiency of prostaglandine E t-stimulated cyclie AMP production, a function known to be inhibited byalpha-receptor stimulation (Kafka and van Kammen 1983). It is not known, however, whether these peripheral findings parallel brain metabolism. Pharmacological receptor manipulation has been another approach to investigate noradrenergie mechansisms, although neuroendocrine responses to pharmacological challenges have not been elucidated in detail (Matusseket aI. 1980). Therefore, we compared endocrine responses ofthe hypothalamie-pituitary-adrenal and -somatotropic axes following clonidine (CLON), a predominantly centrally acting alphaNeceptor agonist, in patients with acute paranoid schizophrenia and healthy subjects, in order to explore alpha-adrenoceptor function in schizophrenia.