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PubMed1992

A highly selective kappa-opioid receptor agonist, CI-977, reduces excitatory synaptic potentials in the rat locus coeruleus in vitro.

Intracellular recordings were made from neurons in a rat locus coeruleus slice preparation in vitro. A postsynaptic potential was evoked by electrical stimulation of afferents to the neurons. CI-977 ([5R-(5a,7a,8b)]-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec -8-yl[-4-benzofuranacetamide monohydrochloride) caused a depression of the evoked postsynaptic potential on locus coeruleus neurons. This action was reversed on washout. Bremazocine had a similar action on less than 50% of locus coeruleus neurons. Concentrations of CI-977 which depressed the postsynaptic potential did not affect either passive membrane conductance or a voltage-sensitive potassium current resembling IA. The depression of the excitatory postsynaptic potential caused by CI-977 remained in the presence of either 30 microM bicuculline and picrotoxin or when potassium acetate-filled recording electrodes were used. Using potassium chloride-filled recording electrodes and in the presence of 30 microM 6-cyano-2,3-dihydro-7-nitroquinoxaline-2,3-dione and either 30 microM DL-2-amino-5-phosphonovaleric acid or 500 microM kynurenic acid, CI-977 had no effect on the postsynaptic potential. The effects of CI-977 were reversed by 30-100 nM naloxone and 1-10 nM norbinaltorphimine but not by 1-10 nM naloxone. The hyperpolarizing response to the mu-opioid receptor-selective agonist D-Ala2,Nme Phe4,Gly-ol5 (DAGOL) was blocked by 1-10 nM naloxone but not by 1-100 nM norbinaltorphimine. The hyperpolarizing response to DAGOL was not affected by high doses of CI-977.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed2001

Patterns of colocalization of GABA, glutamate and glycine immunoreactivities in terminals that synapse on dendrites of noradrenergic neurons in rat locus coeruleus.

Amino acid transmitters play a key role in regulating the activity of noradrenergic neurons in the locus coeruleus. We investigated the anatomical substrate for this regulation by quantifying immunoreactivity for GABA, glutamate and glycine in terminals that contacted the dendrites of tyrosine hydroxylase-immunoreactive principal neurons in rat locus coeruleus. Pre-embedding peroxidase immunocytochemistry was used to detect tyrosine hydroxylase-immunoreactivity in Vibratome sections of tissue perfused with 2.5% glutaraldehyde. GABA, glutamate and glycine were localized with postembedding immunogold labelling. Gold particle densities over terminals were measured in three semiserial ultrathin sections, each reacted for a different amino acid. More than 90% (range among rats, 89%-95%) of the terminals analyzed (n = 288) were immunoreactive for at least one amino acid. A high proportion (39%-49%) were positive for two or three amino acids. About two-thirds (60%-69%) of the boutons contained GABA, of which more than half (51%-55%) also contained glycine. More than one-third (36%-38%) of the terminals were positive for glycine. Terminals immunoreactive for glycine alone were rare (0%-2%). About one-third of the terminals showed glutamate-immunoreactivity (32%-37%). GABA and/or glycine occurred in one-fifth to one-third of these. These results show that amino acid-immunoreactivity is present in almost all of the terminals that synapse on tyrosine hydroxylase-positive dendrites in locus coeruleus. Glutamate provides a major excitatory input. The almost complete colocalization of glycine with GABA suggests that the inhibitory input to locus coeruleus is predominantly GABAergic with a contribution from glycine in about half of the GABAergic boutons.

Afferent Pathways↗
PubMed1991

Synergistic analgesic interactions between the periaqueductal gray and the locus coeruleus.

Opiates modulate pain perception at a number of different levels within the central nervous system and the importance of synergistic spinal and supraspinal influences have been well documented. In the present study we demonstrate synergistic interactions between the periaqueductal gray and locus coeruleus. Administered either systemically or intracerebroventricularly (i.c.v.), ethylketocyclazocine elicits a potent naloxonazine-sensitive analgesia, indicating a mu 1 action. mu 1 Receptors also play a major role in opioid analgesic mechanisms in the periaqueductal gray and the locus coeruleus. However, microinjection of EKC into either the periaqueductal gray or locus coeruleus failed to elicit an analgesic response at any dose tested (0.1-20 micrograms) and, in additional studies, antagonized the analgesic actions of coadministered morphine or [D-Ser2,Leu5]enkephalin-Thr6 (DSLET). However, the simultaneous administration of EKC into both the periaqueductal gray (10 micrograms) and the locus coeruleus (10 micrograms; total combined dose 20 micrograms) produced a potent naloxonazine-sensitive analgesia greater than that observed with 50 micrograms i.c.v. These results suggest that EKC is a partial mu 1 agonist which lacks the efficacy to elicit analgesia when microinjected into either of the two brain regions alone. However, when exposed to several regions at once, either through simultaneous microinjections into the periaqueductal gray and locus coeruleus or by injection into the ventricle, EKC is a potent mu 1 analgesic. These results point out the existence of synergistic supraspinal interactions between the periaqueductal gray and the locus coeruleus, similar to the spinal/supraspinal interactions observed previously.

Analgesics↗
PubMed1988

Synaptic potentials in rat locus coeruleus neurones.

1. Intracellular recordings were made from locus coeruleus neurones in a slice of tissue cut from the rat pons. A depolarizing postsynaptic potential (PSP) followed electrical stimulation of the slice surface; the latency was 1-3 ms and the duration was 50-200 ms. 2. The reversal potential of the PSP (estimated by extrapolation from potentials between -60 and -90 mV) was -27 mV when the recording electrodes contained potassium chloride, and -36 mV when electrodes contained potassium acetate or methylsulphate. 3. Kynurenic acid depressed the PSP amplitude by up to 60%. The residual PSP reversed polarity at -50 mV (extrapolated, potassium chloride in electrodes) or -70 mV (observed, potassium methylsulphate in electrodes): it was blocked by bicuculline (10 microM). 4. Exogenously applied gamma-aminobutyric acid (GABA) depolarized cells when the recording electrode contained potassium chloride (reversal potential was -45 mV) and hyperpolarized cells when the recording electrode contained potassium methylsulphate (reversal potential was -70 mV). 5. In the presence of bicuculline, the residual PSP was blocked by kynurenic acid, whereas DL-2-amino-5-phosphonovaleric acid (2-APV) reduced its amplitude to 80% of control. 6. Exogenously applied glutamate, quisqualate and N-methyl-D-aspartate (NMDA) all caused a membrane depolarization (or an inward current under voltage clamp) which reversed polarity at about 0 mV. These effects were blocked by kynurenic acid (500 microM); 2-APV (50 microM) selectively blocked the effect of NMDA. 7. The results indicate that the PSP evoked by focal stimulation within the nucleus locus coeruleus results from an excitatory amino acid acting predominantly at non-NMDA receptors, and from GABA acting at GABAA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1995

Localization of corticotropin-releasing hormone in the human locus coeruleus and pedunculopontine tegmental nucleus: an immunocytochemical and in situ hybridization study.

The present study utilized immunocytochemistry and in situ hybridization histochemistry to examine the localization of corticotropin-releasing hormone immunoreactivity and messenger RNA in neurons of the human brainstem. A large population of corticotropin-releasing hormone-immunoreactive neurons appeared in the lateral region of the pontomesencephalic tegmentum. These corticotropin-releasing hormone-containing neurons are predominantly located in the compact subnucleus of the pedunculopontine tegmental nucleus. Proceeding caudally, corticotropin-releasing hormone-immunoreactive neurons in the pedunculopontine tegmental nucleus travel in a dorsomedial direction approaching the ventral border of the locus coeruleus in a dispersed fashion and cluster in a region ventromedial to the locus coeruleus which corresponds to the ventral aspect of the laterodorsal tegmental nucleus. Dense corticotropin-releasing hormone-immunoreactive fibers are present in the dorsal portion of the locus coeruleus and are most prominent in the middle to rostral levels of the nucleus. The cellular and regional localization of corticotropin-releasing hormone messenger RNA in the human brainstem is identical to the perikaryal distribution visualized by immunocytochemistry. Neurons in the laterodorsal tegmental nucleus and pedunculopontine tegmental nucleus express abundant levels of corticotropin-releasing hormone messenger RNA as revealed by dense silver grains overlying these neurons on the emulsion autoradiograms. Within the locus coeruleus, the cellular expression of corticotropin-releasing hormone-immunoreactive and corticotropin-releasing hormone messenger RNA is exclusively localized to non-pigmented neurons. The present study confirms a previous finding describing dense corticotropin-releasing hormone-immunoreactive fibers innervating the human locus coeruleus and extends these findings by identifying corticotropin-releasing hormone immunoreactive and corticotropin-releasing hormone messenger RNA-containing perikarya in the pedunculopontine tegmental nucleus, in the ventral portion of the laterodorsal tegmental nucleus and in the locus coeruleus proper. From morphological observations, the corticotropin-releasing hormone-containing neurons in human pontomesencephalic tegmentum form a continuous population of neurons that are positioned anatomically to exert a putative neuromodulatory influence on locus coeruleus neurons.

Adult↗
PubMed1999

Stress-induced C-fos expression in the rat locus coeruleus is dependent on neurokinin 1 receptor activation.

These experiments examined the role of substance P-selective neurokinin 1 receptors in the restraint-induced activation of the rat locus coeruleus. Immunohistochemistry revealed high levels of neurokinin 1 receptor expression in the plasma membrane of tyrosine hydroxylase-positive locus coeruleus neurons. The selective neurokinin 1 receptor antagonists, RP 67580 (5 nmol) and L-760,735 (3.4 nmol), were administered intracerebroventricularly prior to restraint stress, and c-fos protein was measured as an index of locus coeruleus activation. Both antagonists attenuated the restraint-induced increase in locus coeruleus c-fos expression, whereas their inactive enantiomers were ineffective. These results suggest that neurokinin 1 receptors may mediate activation of locus coeruleus neurons during stress. Neurokinin 1 receptor antagonists may prove to be novel therapeutic compounds in the treatment of anxiety and depression.

Animals↗
PubMed1988

Pertussis toxin blocks the effects of alpha 2-agonists and antagonists on locus coeruleus activity in vivo.

This study assessed the effects of pertussis toxin, which is known to inactivate G proteins and therefore to block receptors linked to G proteins, on electrophysiological activity of the locus coeruleus in vivo. Pertussis toxin was injected into the lateral cerebral ventricle of rats, and locus coeruleus activity was then recorded. Compared to vehicle-injected control animals, pretreatment with pertussis toxin markedly increased the spontaneous firing rate of locus coeruleus neurons. In addition, the alpha 2-antagonist idazoxan was no longer able to augment either spontaneous or evoked locus coeruleus activity after pretreatment with pertussis toxin. Finally, pretreatment with pertussis toxin made locus coeruleus neurons resistant to inhibition by the alpha 2-agonist clonidine. These results are consistent with the view that pertussis toxin blocks alpha 2-receptors, receptors linked to G proteins, in vivo.

Adrenergic alpha-Agonists↗
PubMed1997

Pharmacology and distribution of norepinephrine transporters in the human locus coeruleus and raphe nuclei.

The norepinephrine transporter (NET) is a site of action for tricyclic antidepressant drugs and for drugs of abuse such as amphetamine and cocaine. In this study, the binding of [3H]nisoxetine to NETs in the noradrenergic cell group, the locus coeruleus, and the serotonergic cell groups, the dorsal raphe nuclei, was measured autoradiographically in postmortem human brain. [3H]nisoxetine binding was unevenly distributed along the rostral-caudal axis of the locus coeruleus and correlated positively with numbers of neuromelanin-containing (noradrenergic) cells along the axis of the locus coeruleus within individuals. Binding densities of [3H]nisoxetine in dorsal raphe nuclei were similar to that in the locus coeruleus. [3H]nisoxetine binding was unevenly distributed along the entire rostral-caudal extent of the dorsal raphe, with the highest binding occurring in the interfascicular and ventral nuclei. A moderate amount of [3H]nisoxetine binding was also observed in the median raphe nucleus. The specificity of [3H]nisoxetine binding to NETs in monoaminergic nuclei was assessed by measuring the inhibition of its binding by desipramine, imipramine, or citalopram. The order of affinities of these drugs was identical in the locus coeruleus and dorsal and median raphe and was characteristic of binding to NETs (desipramine > imipramine > citalopram). Thus, high levels of NETs and an uneven distribution of NETs occur in the locus coeruleus as well as in the dorsal raphe nuclei of the human.

Adult↗
PubMed1987

Comparative investigations on the actions of ACTH1-24, somatostatin, neurotensin, substance P and vasopressin on locus coeruleus neuronal activity in vitro.

A considerable number of neuropeptides have been localized immunohistochemically in the area of the locus coeruleus of the rat. The objective of this study was to assess the actions of some of these transmitter candidates on spontaneously active locus coeruleus neurons in vitro. The effects of bath-applied peptides on the discharge rate of individual locus coeruleus neurons were investigated. A midpontine slice preparation of the gerbil brain was used. Excitatory dose-dependent effects were found with four peptides with the following rank order of potency: Substance P, (Arg8)-vasopressin, neurotensin, ACTH1-24. Somatostatin hyperpolarized all neurons tested. Given the pronounced effects seen with substance P, somatostatin and vasopressin in the nanomolar range, it is conceivable that these peptides may have a role in regulating neuronal activity in locus coeruleus.

Animals↗
PubMed1986

Infusion of adrenergic receptor agonists and antagonists into the locus coeruleus and ventricular system of the brain. Effects on swim-motivated and spontaneous motor activity.

These studies examined how pharmacological stimulation and blockade of alpha receptors would affect active motor behavior in rats. In experiment I, alpha-2 receptor antagonists (piperoxane, yohimbine) and agonists [clonidine, norepinephrine (NE)] were infused into various locations in the ventricular system of the brain, including the locus coeruleus region, and motor activity was measured. Activity was measured principally in a swim test but spontaneous (ambulatory) activity was also recorded while drugs were being infused. When infused into the locus coeruleus region, small doses of the antagonists piperoxane and yohimbine depressed activity in the swim test while infusion of the agonists clonidine and NE had the opposite effect of stimulating activity. These effects were highly specific to the region of the locus coeruleus, since infusions of these drugs into other nearby locations in the ventricular system or use of larger doses had different, often opposite effects. This was especially true of clonidine and NE which profoundly depressed activity when infused posterior to the locus coeruleus, particularly over the dorsal vagal complex. Infusion of small doses of these drugs into the lateral ventricle had effects similar to infusion into the locus coeruleus region, though less pronounced. Changes in spontaneous motor activity were also observed, but this measure differentiated the groups less well than did the swim test. In experiment II, the predominantly postsynaptic receptor agonists isoproterenol (beta agonist) and phenylephrine (alpha-1 agonist) were infused into the ventricular system. Since infusions of piperoxane and yohimbine into the locus coeruleus that decreased activity in experiment I increase the release of NE by blocking alpha-2 inhibitory receptors on cell bodies and dendrites of the locus coeruleus, experiment II tested whether ventricular infusion of predominantly postsynaptic receptor agonists would also decrease activity in the swim test. Both isoproterenol and phenylephrine produced this effect, but did so selectively with respect to dose and location of infusion in the ventricular system. These findings are consistent with recent results relating to the mechanism that underlies stress-induced depression of active behavior.

Adrenergic alpha-Agonists↗
PubMed1987

Cerebellum plus locus coeruleus in tissue culture. II: Development and metabolism of catecholamines.

In contrast to locus coeruleus neurons in vivo, dopamine was the predominant catecholamine synthesized, stored, and released by neonatal mouse locus coeruleus cultures which included target cerebellar tissue, and norepinephrine was present in these cultures only at very low levels. Developmentally, norepinephrine increased slightly in the explants during the first 4 days in vitro and declined thereafter to barely detectable levels, whereas dopamine began to rise after 4 days and reached maximal levels by 7 days. Dopamine beta-hydroxylase was present in these cultures throughout maturation. These results suggest that the high ratio of dopamine to norepinephrine in locus coeruleus cultures cannot be attributed to the absence of appropriate target tissue or to a lack of the enzyme, dopamine beta-hydroxylase.

Animals↗
PubMed1973

Impaired learning and decreased cortical norepinephrine after bilateral locus coeruleus lesions.

Bilateral lesions of the nucleus locus coeruleus in rats deplete the cerebral cortex of norepinephrine and significantly diminish the rate of increase of running for food reward in a simple L-shaped runway. As assessed in this situation, learning was absent in those rats with the most complete ablations of the locus coeruleus, although these rats showed normal weight gain and normal motor and exploratory activity.

Animals↗
PubMed2003

Potentiation of parkinsonian symptoms by depletion of locus coeruleus noradrenaline in 6-hydroxydopamine-induced partial degeneration of substantia nigra in rats.

Parkinson's disease is characterized not only by a progressive loss of dopaminergic neurons in the substantia nigra but also by a degeneration of locus coeruleus noradrenergic neurons. The present study addresses the question of whether a partial neurodegeneration of dopaminergic neurons using 6-hydroxydopamine in rat, not sufficient to produce motor disturbances, is potentiated by prior selective denervation of locus coeruleus noradrenergic terminal fields using N-ethyl-2-bromobenzylamine. Two types of denervations, one causing dopamine deficiency alone and the other causing noradrenaline and dopamine deficiency, were performed. Noradrenaline, 5-hydroxytryptamine, 5-hydroxyindole acetic acid, dopamine and its metabolites were analysed in various brain regions. Behaviour was evaluated by catalepsy tests and activity box. N-ethyl-2-bromobenzylamine selectively depleted noradrenaline from neurons of locus coeruleus origin. Decreased dopamine content in the striatum, substantia nigra and pre-frontal cortex was observed after dopaminergic lesion with 6-hydroxydopamine (42.9%). Additional locus coeruleus noradrenaline depletion with N-ethyl-2-bromobenzylamine aggravated the dopamine depletion (61.2%). The lesion in the noradrenergic and dopaminergic neurodegenerated group was not sufficient to induce consistent catalepsy and akinesia. However, after a subthreshold dose of haloperidol (0.1 mg/kg), the expression of catalepsy and akinesia was strong in the dual-lesioned group and less in the 6-hydroxydopamine-lesioned group. These results indicate that denervation of locus coeruleus noradrenergic terminals with N-ethyl-2-bromobenzylamine potentiates the 6-hydroxydopamine-induced partial dopaminergic neurodegeneration and parkinsonian symptoms. Based on the present findings and existing reports, it can be concluded that noradrenergic neurons of locus coeruleus have neuromodulatory and neuroprotective properties on the dopaminergic neurons of basal ganglia and that noradrenergic degeneration may contribute to the aetiology and pathophysiology of Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Action of dexmedetomidine on rat locus coeruleus neurones: intracellular recording in vitro.

The action of dexmedetomidine on rat locus coeruleus neurones was examined using intracellular recordings from the in vitro brain slice preparation. Concentrations of dexmedetomidine from 1 to 1000 nM were tested. At 30 nM, dexmedetomidine produced complete inhibition of firing of all neurones tested (n = 21); this was associated with a 13 mV hyperpolarization (range 2.2-29.7 mV, n = 21) and a 27% reduction in input resistance (range 11.1-46.2%, n = 17). The dexmedetomidine responses reached a plateau phase between 100 and 1000 nM. Based on single-cell recordings, the hyperpolarizing potency of dexmedetomidine was found to be 6 times greater than that of clonidine (n = 10). The reversal potential for the dexmedetomidine-induced hyperpolarization was -106.9 +/- 1.7 mV (n = 9), a value similar to the K+ equilibrium potential; hyperpolarization was blocked by both CsCl and BaCl2. The effect of dexmedetomidine was antagonized by yohimbine, with a dissociation equilibrium constant of 30 nM. In contrast, prazosin, the alpha 1-, alpha 2B- and alpha 2C-adrenoceptor subtype-preferring ligand, did not inhibit the dexmedetomidine effect. Our results also show that low concentrations of oxymetazoline (10-300 nM), an alpha 2A-adrenoceptor subtype-selective drug, cause profound inhibition of neuronal activity in the locus coeruleus. These data therefore suggest that dexmedetomidine binds to alpha 2A-adrenoceptors on the cell membrane of neurones of the locus coeruleus and that this leads to opening of the inwardly rectifying K+ channels, resulting in the observed hyperpolarization of the membrane.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2006

The locus coeruleus nucleus as a site of action of the antinociceptive and behavioral effects of the nicotinic receptor agonist, epibatidine.

The mechanisms and sites of action of epibatidine-induced antinociception and side effects are poorly understood. The present study tested the hypothesis that the locus coeruleus is a site of action of epibatidine. Behavioral responses of rats to hindpaw formalin injection were compared after direct administration of epibatidine into the locus coeruleus (LC), and after subcutaneous administration. Different groups of rats were injected with formalin into the rear paw after administration of either ACSF, epibatidine (0.01, 0.06, 0.12, and 0.3mug) into the locus coeruleus or epibatidine (2.5-5mug/kg) subcutaneously. Assessment of pain-related behavior was done by evaluating the incidence of favoring, lifting and licking of the injected paw in the different groups. Abnormal motor behavior was also recorded. Infusion of epibatidine into LC induced analgesia, which was reversed by prior infusion of mecamylamine into LC. Epibatidine into the locus coeruleus resulted in a significant lower pain score in the second phase of the formalin test compared to control rats and was as effective as subcutaneous epibatidine. The analgesic effects of epibatidine were regionally selective in that the administration of epibatidine outside the locus coeruleus area was not analgesic. The every tested dose of epibatidine administered into the locus coeruleus also produced freezing behavior immediately after injection, which was relatively short-lived compared to the analgesic effect. Freezing was inhibited by administration of mecamylamine into the LC. Together the results implicate the LC as a target for the analgesic effects of epibatidine.

Analgesics↗
PubMedDate not supplied

Effects of acute and short-term administration of tryptophan plus ethanol on noradrenaline and serotonin metabolites in the locus coeruleus.

The effects of acute and short-term administration of tryptophan or tryptophan plus ethanol on serotonin [5-hydroxytryptamine (5-HT)] and two of its metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and 5-hydroxytryptophol (5-HTPL), in the locus coeruleus were investigated in rats by using the microdialysis method. In addition, the acute effects of these drugs on noradrenaline and its metabolite 4-hydroxy-3-methoxymandelic acid (HMMA) were addressed. A single co-administration of tryptophan (50 mg/kg, i.p.) and ethanol (1.25 g/kg, i.p.) did not change the concentrations of either noradrenaline or its metabolite in the locus coeruleus. In contrast, administration of tryptophan (50 mg/kg, i.p.) for three consecutive days caused an increase in the concentration of 5-HIAA, but not that of 5-HT, in the locus coeruleus. Combined administration of tryptophan plus ethanol for 3 days resulted in marked increases in 5-HIAA concentrations in the locus coeruleus, but not in 5-HTPL concentrations. However, administration of ethanol (1.25 g/kg) for 3 days had no effect on the concentrations of 5-HT and its metabolites. The increased 5-HIAA concentration that resulted with combined tryptophan plus ethanol administration was remarkably suppressed by disulfiram. Moreover, in comparison with tryptophan-treated rats, the behavioral sign of teeth-chattering was significantly detected in tryptophan plus ethanol-treated rats, but the enhancement of behavioral signs with combined treatment was markedly suppressed by disulfiram. Results of the current study seem to indicate that the stimulation of 5-HT metabolism in locus coeruleus serotonergic neurons by tryptophan was strengthened by the simultaneous administration of ethanol in short-term experiments, and that the increased 5-HIAA concentrations in the locus coeruleus are responsible for behavioral activation.

Animals↗
PubMed1994

Bilateral 6-OHDA lesions of the locus coeruleus impair associative olfactory learning in newborn rats.

On postnatal day 4 (PN4) Wistar rat pups were anesthetized and received bilateral infusions of 6-OHDA into the locus coeruleus or received vehicle infusions. On PN6 pups were trained in a classical conditioning paradigm with intra-oral milk infusions as the UCS and citral odor as the CS. Pups were trained in either 'paired', 'odor-only', 'milk-only' or 'backward' (milk then odor) conditions. On PN7 acquisition of a learned odor preference to the CS was tested in a two-odor choice test. HPLC analysis showed that locus coeruleus lesions significantly reduced olfactory bulb NE content but had no effect on olfactory bulb DA or 5-HT levels compared to controls. Pups receiving locus coeruleus lesions did not differ in behavioral response patterns during training compared to their littermate, vehicle controls. However, locus coeruleus lesions impaired acquisition of conditioned odor preferences. These results suggest that NE output from the locus coeruleus is critical for early olfactory learning.

Analysis of Variance↗
PubMed1999

Lack of association between depression and loss of neurons in the locus coeruleus in Alzheimer disease.

BACKGROUND: Depression, one of the most frequent psychiatric disturbances in Alzheimer disease (AD), is proposed to have its neurobiological basis in neuron loss in the noradrenergic locus coeruleus, although this is not the case in idiopathic depression. METHODS: We performed image analyzer-assisted morphometry of the locus coeruleus in 6 depressed, 6 transiently depressed, and 6 nondepressed patients with AD and in 8 control subjects, emphasizing longitudinal psychiatric evaluations and matching for the clinical and neuropathological severity of dementia. RESULTS: The mean (+/-SD) number of pigmented neurons in the locus coeruleus in controls (11 607+/-946) was higher than in patients with AD, regardless of being depressed (5165+/-928; P=.001), transiently depressed (5647+/-1163; P=.003), or nondepressed (3717+/-661; P=.001). No significant difference was found in the number of pigmented neurons between patients with AD who were depressed, transiently depressed, and nondepressed. Patients who had depression at the onset of AD had a higher pigmented neuron number than other patients with AD. CONCLUSIONS: We confirmed the loss of pigmented neurons in the locus coeruleus of patients with AD; however, no supplementary loss of pigmented neurons in the locus coeruleus was found in patients with depression and AD. This finding resembles the situation in idiopathic depression, but is in contrast with earlier studies on depression in AD.

Aged↗