Brain Noradrenaline Systems Research Articles

Noradrenaline: Sleep on it

Sleep involves infra-slow ∼50-second fluctuations between disengagement and sensory reactivity. New findings reveal that the brain's noradrenaline system controls these dynamics by acting in the thalamus to affect sleep spindles, and by modulating coordinated heart rate variations.

不安と脳内ノルアドレナリン神経系(不安と抑うつの基礎と臨床)(第37回日本心身医学会総会)

不安と脳内ノルアドレナリン神経系(不安と抑うつの基礎と臨床)(第37回日本心身医学会総会)

Causes of changes in brain noradrenaline systems and later effects on responses to social stressors in rhesus monkeys: the cascade hypothesis.

Disruption of social attachments in social primates produces a protest-despair response. In rhesus monkeys, the response is probably adaptive in the feral environment, although the despair stage resembles human depression in many respects. The severity of the response varies between individuals and is affected by deprivation of certain classes of social stimuli during development. Social deprivation is associated with differences in the concentrations of noradrenaline (NA) in cerebrospinal fluid and in responses to agents that affect catecholamine systems. Thus, early rearing conditions and pre-existing genetic or perinatal differences between monkeys can have long-term effects on the response to social separation, and NA system release and/or receptor mechanisms are involved. NA systems appear to mediate adaptation to the environment from the level of perception to reorganization of neural tissue. Adaptation to the social environment may involve a cascade of changes that begins with behavioural coping attempts and terminates in structural reorganization of regions of the cerebral cortex. Processes at each level occur within environmentally appropriate but neurobiologically constrained time-frames. The cerebral NA system may be an adaptive mechanism that can fail or be damaged. Behavioural changes caused by such damage or failure would be manifested by inappropriate responses to environmental contingencies and inability to change behaviour to adapt to the prevailing environment. These features of NA system disorder could be common to depression and several other forms of human psychopathology.

Oestrogen upregulates noradrenaline release in the mediobasal hypothalamus and tyrosine hydroxylase gene expression in the brainstem of ovariectomized rhesus macaques.

Noradrenaline plays a key role in the initiation of ovulation in nonprimate species. A similar noradrenaline role in the primate has not been established experimentally. We utilized the ovariectomized-oestrogen-supplemented (OVX + E) rhesus macaque to examine the effects of intravenous (i.v.) infusion of oestradiol-17beta (E2) on the activity of the brain noradrenaline system. Experiment 1 established the induction of a preovulatory surge-like release of luteinizing hormone in OVX + E monkeys by i.v. infusion of E2 (OVX + E + E2). In experiment 2, a marked increase in hypothalamic microdialysate noradrenaline concentrations occurred after identical E2 infusion into the OVX + E monkeys that were used in experiment 1. In experiment 3, tyrosine hydroxylase (TH) mRNA expression in the locus coeruleus of the brainstem increased at various times after E2 infusion as determined by semiquantitative in situ hybridization. The amount of TH mRNA in OVX + E + E2 animals was higher (P < 0.05) than that in either the OVX + E or OVX monkeys; no difference was found in the latter two groups. Moreover, selected locus coeruleus sections from E2-infused monkeys were examined for the localization of oestrogen receptors (ER) by in situ hybridization. Both ER-alpha and ER-beta mRNAs were expressed in the locus coeruleus, although the expression was greater for ER-alpha than for ER-beta. We conclude that i.v. infusion of E2, which induces a preovulatory surge-like release of LH, stimulates brain noradrenaline activity; this enhanced activity likely involves an ER-mediated process and is reflected by hypothalamic noradrenaline release and locus coeruleus TH mRNA expression. The results support the concept that noradrenaline can influence the E2-stimulated ovulation in nonhuman primates and that the brainstem is one of the components in this neuroendocrine process.

Stress-induced emotional changes and the brain noradrenaline system in the rat

Stress-induced emotional changes and the brain noradrenaline system in the rat

Involvement of the Brain Noradrenaline System in Emotional Changes Caused by Stress in Ratsa

Involvement of the Brain Noradrenaline System in Emotional Changes Caused by Stress in Rats^a

Relation between brain monoamine oxidase (MAO) activity and the firing rate of locus coeruleus neurons.

Utilizing a specific "low substrate concentration technique", intrasynaptosomal MAO-A and MAO-B activities within the rat brain noradrenaline system were studied. It was found that mainly MAO-A was localized intrasynaptosomally, whereas MAO-B contributed with less than 15% of the total intrasynaptosomal MAO activity, a phenomenon that was also observed within the central dopamine system. It is suggested that the intrasynaptosomal pool of MAO in the noradrenaline and the dopamine systems may reflect the density of innervation of the respective system throughout the brain. In addition, the effects of various selective monoamine oxidase (MAO) inhibitors on the noradrenergic intrasynaptosomal MAO activity as well as on the neuronal firing rate of noradrenaline containing cells in the locus coeruleus (LC) were investigated. Pretreatment with the MAO-A selective inhibitors clorgyline (10 mg/kg, i.p., 1 h) or (+)-FLA 336 (1 mg/kg, i.p., 1 h) caused a significant depression (40%) of mean spontaneous firing rate of LC neurones, randomly encountered throughout the LC. The MAO-B selective inhibitor pargyline (10 mg/kg, i.p., 1 h) was found to lack effect in this regard. However, pretreatment with (-)-deprenyl (10 mg/kg, i.p., 1 h), equally a selective MAO-B inhibitor, markedly suppressed the spontaneous firing rate of LC units. This inhibition by (-)-deprenyl was blocked by pretreatment with SK&F 525 A (50 mg/kg, i.p., 30 min), an inhibitor of microsomal drug metabolizing enzymes. Thus, the depression of LC units by (-)-deprenyl seems to be executed by a metabolite, e.g. l-amphetamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain noradrenaline and the development of hypertension: the effect of treatment with central 6-hydroxydopamine or DSP-4.

The relative role of brain catecholamines in the development of hypertension in the spontaneously hypertensive rat (SHR) was studied. Treatments consisted in five weeks old SHR of central injections of 6-hydroxydopamine (6-OHDA), 3 X 200 micrograms either intracerebroventricularly (i.c.v.) or intracisternally (i.c.), or of intraperitoneal (i.p.) injections of DSP-4, either once or three times 50 mg/kg. Compared to the pronounced attenuation of the development of hypertension following i.c.v. 6-OHDA treatment, the i.c. 6-OHDA treatment and the multiple DSP-4 treatment were less effective. A single injection of DSP-4 had only minor effects on blood pressure. Heart rate was markedly lower in i.c.v. 6-OHDA treated SHR, but the other treatments induced no effects on this parameter. Noradrenaline depletion was found in various parts of the brain particularly after i.c.v. 6-OHDA or either DSP-4 treatment. Brain dopamine and adrenaline were depleted to a lesser extent. However, the best correlation between blood pressure and brain catecholamine concentration was found for dopamine in the hippocampus and hypothalamus and for adrenaline in the hypothalamus. Noradrenaline levels were also correlated with blood pressure, but to a lesser extent. These results suggest that the depletion of dopamine or adrenaline in the brain may be of more importance in the effects of neurotoxic treatments on the development of hypertension than the effects on brain noradrenaline. Thus, these experiments lend support to the hypothesis that brain noradrenaline systems may not play an important role in the development of hypertension in the SHR.

Chronic and acute administration of typical and atypical antidepressants on activity of brain noradrenaline systems in the rat thiopentone anaesthesia model.

A behavioural model sensitive to manipulation of brain noradrenaline systems and with characteristics of beta-receptor mediation has been developed using the duration of thiopentone anaesthesia in the rat. Acute and chronic administration of various antidepressant agents was examined. In the acute phase, (30 min prior to thiopentone) the noradrenaline uptake-inhibiting tricyclic drugs and viloxazine increased anaesthesia duration in a dose-dependent fashion. The atypical antidepressants trazodone, iprindole, and mianserin did this only weakly, while the dopaminergic and serotonergic uptake-inhibiting antidepressants (respectively bupropion, nomifensine, and zimelidine, fluoxetine) markedly shortened anaesthesia duration. Chronic administration (for 15 days) prolonged anaesthesia duration measured 2 or 5 days after the last drug injection for all tricyclic agents, for the atypical antidepressants mianserin, iprindole, fluoxetine, and zimelidine, and for viloxazine.

Behavioural evidence that chronic treatment with the antidepressant desipramine causes reduced functioning of brain noradrenaline systems.

A behavioral system sensitive to the net functional activity of the locus coeruleus noradrenergic system, with characteristics of a beta-adrenoceptor mediated response, has been developed based on the duration of thiopentone anaesthesia in the rat. The effects of acute and chronic treatment with the tricyclic antidepressant desipramine (DMI) were determined. Acute DMI from 5 to 25 mg/kg increased thiopentone sleeping-time in a dose-dependent fashion. This was due to an action on noradrenergic systems, since it was mimicked by treatment with the selective neurotoxin 6-hydroxydopamine, which itself increased thiopentone sleeping-time and prevented any additional effect of DMI. Chronic treatment with DMI had no effect on thiopentone sleeping-time when carried out for 2 or 5 days but markedly prolonged it when carried out for 10 or 20 days, thus paralleling the time course of clinical action of the drug.