Brain Noradrenaline and Schizophrenia

Brain Noradrenergic Receptors in Major Depression and Schizophrenia

“…One of those could be a defect in the noradrenergically controlled attentional (stimulus filtering) mechanisms of the locus coeruleus noradrenergic dorsal bundle that innervates the limbic forebrain area and the hippocampus. The second mechanism could be an alteration in the noradrenergic control of brain dopaminergic systems that generate motivational responses (see Hornykiewicz 1986). Our data support the hypothesis of noradrenergic overactivity in schizophrenia that leads to a down-regulation of beta-1 adrenoceptors in the hippocampus, and indicate that alterations in central noradrenergic transmission may contribute to the neurochemical pathology of schizophrenia.…”

“…An elevation of norepinephrine in the cerebrospinal fluid of schizophrenics compared to controls has also been reported (Gomes et al 1980;Lake et al 1980;Sternberg et al 1981;Van Kammen et al 1989). Interestingly, measures of noradrenergic activity seem to be good indicators and/or predictors of the state of disease and its outcome (Hornykiewicz 1982(Hornykiewicz , 1986Van Kammen and Kelley 1991).…”

“…Evidence that norepinephrine regulates dopamine-induced behaviors in laboratory animals (Mason 1981;Plaznik et al 1982) provides a potential link of norepinephrine to dopaminergic dysfunction in schizophrenia. Interestingly, elevated norepinephrine output has been observed in schizophrenic patients (Lake et al 1980;Sternberg et al 1981;Hornykiewicz 1982Hornykiewicz , 1986Van Kammen and Antelman 1984).…”

“…Schizophrenia was of particular interest, given evidence implicating a potential role of norepinephrine in the pathophysiology of this disorder. A disruption of the activity of the noradrenergic dorsal bundle from locus coeruleus to the forebrain limbic system could be a possible contributor to the schizophrenic disturbance (see Hornykiewicz 1986;Weinberger et al 1983), given that activity of the dorsal bundle of the locus coeruleus normally serves to screen the incoming sensory stimuli, filtering out and discarding information irrelevant to the task at hand (Archer et al 1982;Mason 1981). Evidence that norepinephrine regulates dopamine-induced behaviors in laboratory animals (Mason 1981;Plaznik et al 1982) provides a potential link of norepinephrine to dopaminergic dysfunction in schizophrenia.…”

“…For example, hippocampal beta-1 adrenoceptors down-regulate in rats following pharmacological treatments that elevate synaptic norepinephrine (Sulser et al 1984;Ordway et al 1991). Elevated concentrations of norepinephrine have been detected postmortem in limbic forebrain (Farley et al 1978;Bird et al 1979;Hornykiewicz 1986) in schizophrenic subjects as compared to control subjects. An elevation of norepinephrine in the cerebrospinal fluid of schizophrenics compared to controls has also been reported (Gomes et al 1980;Lake et al 1980;Sternberg et al 1981;Van Kammen et al 1989).…”