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PubMed1983

Immunocytochemical localization of TRH and autoradiographic determination of 3H-TRH-binding sites in the arcuate nucleus-median eminence of the rat.

Immunocytochemical and autoradiographic localization of thyrotropin-releasing hormone (TRH)- and 3H-TRH-binding sites was studied in the arcuate nucleus-median eminence region of the rat. TRH-like immunoreactivity was found in dense granular vesicles (90-140 nm in diameter) in TRH-like immunoreactive nerve fibers and terminals. In the median eminence, the immunoreactive terminals were observed to be in direct contact with the perivascular basal lamina of the portal vessel and to form synaptoid contacts with tanycytes. In the arcuate nucleus, the immunoreactive terminals were often found to form axosomatic and axo-axonic, and/or axo-dendritic synapses. The uptake of tritiated TRH into the nerve fibers and terminals of the median eminence was also observed by autoradiography and the distribution and localization of silver grains in them were analyzed quantitatively by circle analysis. Thirty minutes after intraventricular infusion of 3H-TRH, radioactive labeling occurred in type-2 and 3-nerve fibers and terminals containing dense granular vesicles in the median eminence. It is therefore suggested that the neurons labeled after 3H-TRH infusion possess certain functions as physiological recognition sites or receptors for TRH.

Animals↗

PubMed1978

Ultrastructural localization of radiolabelled L-dopa in the endocrine hypothalamus of the rat.

Light and electron microscopic autoradiography has been employed to define the neuroanatomical patterns of uptake and binding of radiolabelled L-dopa in the endocrine hypothalamus of the rat. A dorsomedial continuum of arcuate and periventricular neurons selectively sequester 3HL-dopa 20 min following its intraventricular infusion. By 40 and 60 min following the infusion labelling of neurons is minimal and supports the notion of rapid degradation. Other cell compartments such as tanycytes demonstrate uptake of 3H L-dopa. The ultrastructural localization and distribution of radiolabelled L-dopa (or its metabolites) in the rodent hypothalamus is discussed with respect to mechanisms and cell compartments involved in neuroendocrine regulatory processes.

Animals↗

PubMed1979

Quantative radioautographic light and electron microscopic analysis of the localization of monoamines in the median eminence of the rat.

Serotonin containing structures in the median eminence of the rat have been studied by quantitative light and electron microscopic radioautography following intraventricular infusion of tritiated 5-hydroxytryptophan. One hour after injection of the tracer the highest density of silver grains was recorded in the ependymal and external zones, especially in the lateral palisade zone. The proportion of labelled neurosecretory terminals was also larger in the lateral palisade zone (29%) as compared with the medial palisade zone (13%), although the mean number of developed silver grains per one terminal was higher in the latter. On the average, 16% of neurosecretory terminals sequestered radiolabelled 5-hydroxytryptophan in the external zone of the rat median eminence. It is suggested that serotonin, like catecholamines, is discharged from neurosecretory terminals localized in the external zone and via the portal circulation affects the function of the anterior pituitary. The sites of origin of serotoninergic structures of the median eminence as well as the possible role of monoamine (catecholamine and indolamine) neurohormones in a dual peptidergic and monoaminergic control of anterior pituitary functions are discussed.

Animals↗

PubMed1987

Acquisition of a brief behavioral experience in the presence of neuron-specific and D2-CAM/N-CAM-specific antisera.

The effect of intraventricular infusion of D2-CAM/N-CAM directed antibodies prior to the acquisition of a passive-avoidance paradigm is described. The antisera used in this study were the neuron specific anti-BPM and a D2-CAM/N-CAM specific serum, anti-D2. Anti-BPM reliably inhibited paradigm acquisition when recall was ascertained at 24 and 48 hours and no effect was noted with absorbed anti-BPM or in sham-operated animals. This effect was time-dependent and no inhibition of memory formation was noted when the antiserum was administered at 6 and 10 hours after training. In contrast, infusion of anti-D2 had no effect on paradigm acquisition. These findings are discussed in relation to the potential synaptogenic events associated with memory formation.

Animals↗

PubMed1993

Cholinergic and dopaminergic agents which inhibit a passive avoidance response attenuate the paradigm-specific increases in NCAM sialylation state.

The influence of cholinergic and dopaminergic agents on the acquisition of a passive avoidance response in the rat is demonstrated. Trifluoperazine (0.12 mg/kg), a dopamine antagonist, inhibited task acquisition when present during training or later, during consolidation, at the 10-12 h post-training period and at no other intervening time point. Induction of amnesia was dose-dependent and was not apparent when the dose exceeded 0.12 mg/kg. This effect appears to be due to an increase in dopamine release through presynaptic receptor antagonism as similar results could be obtained by the administration of apomorphine (0.5 mg/kg), a dopamine agonist, and this effect could be antagonized by the D1 receptor selective antagonist SCH-23390. Scopolamine (0.15 mg/kg), a muscarinic antagonist, impaired acquisition of the passive avoidance response when administered during training and, separately, at the 6 h post-training period. This could not be attributed to presynaptic antagonism as oxotremorine (0.2 mg/kg), a muscarinic agonist, had no amnesic action. Administration of apomorphine or scopolamine during training and at the appropriate post-training period prevented subsequent paradigm-specific increases of neural cell adhesion molecule sialylation state in hippocampal immunoprecipitates obtained at 24 h after task acquisition and 4 h following intraventricular infusion of the labelled sialic acid precursor - N-acetyl-D-mannosamine. Oxotremorine alone did not influence neural cell adhesion molecule sialylation state. These observations provide further evidence of a regulatory role for neural cell adhesion molecule sialylation state in information storage processes.

Amnesia↗

PubMed1982

Intercellular junctions between specialized ependymal cells in the subcommissural organ of the rat.

The permeability of intercellular junctions in specialized ependymal cells in the rat subcommissural organ (SCO) has been studied ultrastructurally by freeze-fracturing and tracer experiments with horseradish peroxidase (HRP). In addition to normal smooth membrane, areas which could be classified as a leaky tight junction are found within the ependymal junctional region. This consists of only one or two relatively continuous strands but with interruptions in the apical portion. Some strands are perpendicular to the apical membrane surface and often form hairpin-like bends in the basal portion of the junction. The junctional region also shows areas with no strands but only a rippled membrane structure which may be equivalent to very close appositions without fusion of adjacent ependymal cell membranes. The relative proportions of normal smooth membrane, strands and rippled structure in the junctional region is approximately 3:4:6 including two parts overlapping of the strands and rippled structure. Intraventricularly infused HRP passes through many junctions but is occasionally stopped, leaving unstained intercellular spaces of various lengths between membrane fusions of tight junctions. Even when it is stopped, the intercellular space below the junction is densely stained by the enzyme. Orthogonal arrays of intramembrane particles are found to be distributed on the basal and lateral cell membranes below the junctional region in the SCO ependyma.

Animals↗

PubMed1982

Fine structural studies on ependymal paracellular and capillary transcellular permeability in the subcommissural organ of the guinea pig.

Morphological investigations on the permeability of intercellular junctions between ependymal cells and between capillary endothelial cells in the subcommissural organ (SCO) of the guinea pig have been carried out using freeze-fracturing and tracer experiments with horseradish peroxidase (HRP). The ependymal junction reveals a moderately developed network of tight junctional strands surrounding the tall ependymal cell. The apical portion of this junctional network tends to form nearly complete strands, whereas the basal portion usually shows irregular, fragmented strands often arranged in hairpin-like structures. The passage of intraventricularly infused HRP is blocked, leaving unstained areas, at the level of membrane fusions. At the same time the lateral intercellular space below the junction is densely stained, probably due to invasion from the basal side through adjacent ordinary ependymal junctions. The SCO capillary endothelium shows a high distribution density of pinocytotic vesicles. Vesicular transport of intravascularly injected HRP is observed, but no HRP penetration occurs through the endothelial junction. The active participation of vesicles in tracer movement is shown in preparations fixed before administration of HRP. Extravasation of this tracer is indicated to some degree in the SCO capillary, but permeability here appears to be comparable to that of ordinary brain capillaries. Accordingly, the SCO ependymal tight junction seems to form an effective barrier not to blood plasma or similar materials but to apically secreted substances, preventing them from spreading back into SCO intercellular spaces.

Animals↗

PubMed1987

Ultrastructural organization of regenerated serotonin axons in the dorsomedial hypothalamus of the adult rat.

The ultrastructural organization of regenerated serotonin (5-HT) axons was examined in the dorsomedial hypothalamus (DMH) of the adult rat using high-resolution radioautography after intraventricular infusion of [3H]5-HT. An analysis of the microenvironment of the [3H]5-HT-labelled terminals in the DMH was made 30 and 50 days after unilateral injection of 5,7-dihydroxytryptamine (5,7-DHT) or vehicle solution into the dorsolateral hypothalamus. In sham-treated animals [3H]5-HT-labelled axons were small, contained many small clear vesicles, one or more large granular vesicles, and showed only rare synaptic specializations. In 5,7-DHT-treated animals the internal organization of [3H]5-HT-labelled profiles resembled that of sham-treated animals. A tendency toward increased synaptic frequency was found for [3H]5-HT-labelled terminals in the 5,7-DHT-treated group 50 days post-lesion, and an increase in the number of [3H]5-HT-labelled terminals abutting unlabelled perikarya was found in both 30- and 50-day post-lesion groups as compared to sham-treated groups. No other differences in ultrastructural environment were found between sham- and 5,7-DHT-treated animals at either 30 or 50 days post-lesion. These results suggest that 5-HT fibres in the hypothalamus regenerate with a great deal of cellular specificity.

5,7-Dihydroxytryptamine↗

PubMedDate not supplied

Significance of right ventricular filling for left ventricular enddiastolic pressure-volume relationship under acute hypoxia in the dog.

In 14 closed-chest dogs, the significance of right ventricular filling for left ventricular enddiastolic pressure-volume relationship was investigated under acute hypoxia by means of single plane cineventriculography and simultaneous intraventricular pressure recording. Both after 5 min asphyxia (respirator switched off) (n = 5) and after 3 min hypoxia (ventilation with pure N2) (n = 9), there was a significant leftward shift (p less than 0.005) of the left ventricular enddiastolic pressure-volume curve as compared to the control curves under normoxia. To simulate the elevated filling of the right ventricle under acute hypoxia, rapid intraventricular infusion was applied under normoxic conditions to raise right ventricular enddiastolic pressure to the same values as that measured under hypoxia. The extent of the ensuing leftward shift of the left ventricular enddiastolic pressure-volume curve was on average 60% of the shift under hypoxia in both sets of experiments. Neither the slope of the relationship between volume stiffness and enddiastolic pressure, nor the relationship between tangent elastic modulus and left ventricular wall stress, was affected by hypoxia or asphyxia. Thus, the shift of the left ventricular enddiastolic pressure-volume curve in the early stage of hypoxia is predominantly due to the influence of increased right ventricular filling. Since the increased volume of the atria under acute hypoxia limits left ventricular distensibility additionally, the changes in left ventricular enddiastolic pressure-volume relationships observed in the early stage of hypoxia are mainly, or even entirely, the result of interaction of the various heart compartments, and not a reflection of alterations in myocardial tissue elasticity.

Animals↗

PubMedDate not supplied

Hippocampal damage and cytoskeletal disruption resulting from impaired energy metabolism. Implications for Alzheimer disease.

To determine if impaired energy metabolism might contribute to some aspects of Alzheimer disease (AD), including the vulnerability of the CA1 region of the hippocampal formation and the altered cytoskeleton evident in neurofibrillary tangles, we examined the effects of metabolic poisons on neuronal damage and cytoskeletal disruption in the hippocampal formation. Intrahippocampal injection of 3-nitropropionic acid (3-NP) and malonic acid resulted in neuronal death, particularly in CA1. Cytoskeletal disruption included loss of dendritic MAP2, but sparing of axonal gamma. MK-801 (a noncompetitive NMDA receptor antagonist) did not atentuate the lesions produced by intrahippocampal injection of malonate. MK-801, however, was effective against intrastriatal malonate. Acute systemic 3-NP resulted in neuronal damage and cytoskeletal disruption in the CA1 region of the hippocampal formation, including an extensive loss of MAP2 immuno-reactivity, but sparing of gamma. The neuronal loss in CA1 was delayed as compared to striatum. Chronic intraventricular infusion of 3-NP produced a different pattern of neuronal damage. Loss of gamma-1 immuno-reactivity was observed in CA3 and CA1 s. orients, whereas MAP2 immunostaining was preserved. These results demonstrate that chronic and acute administration of metabolic inhibitors produce distinct patterns of neuronal damage and cytoskeletal disruption. The results further suggest a differential involvement of the NMDA receptor in malonate-induced neuronal damage in striatum as compared to the hippocampus. The pattern of neuronal damage and cytoskeletal disruption observed following acute metabolic impairment resembled some aspects of neurofibrillary pathology in AD, but did not result in gamma hyperphosphorylation.

Alzheimer Disease↗

PubMed2002

Nerve growth factor improves spatial learning and restores hippocampal cholinergic fibers in rats withdrawn from chronic treatment with ethanol.

The cholinergic septohippocampal pathway has long been known to be important for learning and memory. Prolonged intake of ethanol causes enduring memory deficits, which are paralleled by partial depletion of hippocampal cholinergic afferents. We hypothesized that exogenous supply of nerve growth factor (NGF), known to serve as a trophic substance for septal cholinergic neurons, can revert the ethanol-induced changes in the septohippocampal cholinergic system. Adult rats were given a 20% ethanol solution as their only source of fluid for 6 months. During the first 4 weeks after the animals were withdrawn from ethanol, they were intraventricularly infused with either NGF or vehicle alone via implanted osmotic minipumps. The vehicle-infused withdrawn animals showed impaired performance on a spatial reference memory version of the Morris water maze task, both during the task acquisition and on the retention test. In contrast, NGF-treated withdrawn rats were able to learn the task as well as controls, and significantly outperformed the vehicle-infused withdrawn rats. The histological analysis revealed that, in the latter group, the length density of fibers immunoreactive to choline acetyltransferase was reduced relative to control values by approximately 25%, as measured in the dentate gyrus and regio superior of the hippocampal formation. However, in NGF-treated withdrawn rats, the length density of these fibers was identical to that of control rats. These data provide support to the notion that NGF is capable of ameliorating memory deficits and restoring septohippocampal cholinergic projections following chronic treatment with ethanol.

Afferent Pathways↗

PubMed1997

Characterization of a prolonged regenerative attempt by diffusely injured axons following traumatic brain injury in adult cat: a light and electron microscopic immunocytochemical study.

Traumatic brain injury in animals and humans is well known to cause axonal damage diffusely scattered throughout the brain without evidence of other brain parenchymal change. This observation has prompted some to posit that such damaged axons are well positioned to mount a regenerative attempt. The present study uses an immunocytochemical marker specific for regenerating neurites to explore this issue. Further, in an attempt to expedite and enhance any potential regenerative effort, this study evaluates the efficacy of intrathecally applied nerve growth factor. Three sets of experiments were performed in adult cats. One group of animals was subjected to moderate fluid percussion brain injury and followed for 7 or 14 days post injury, with the continuous intraventricular infusion of nerve growth factor delivered by implanted osmotic pumps. These animals were compared to a second group of time-matched, sham-operated animals receiving artificial cerebrospinal fluid infusion. To assess axonal damage immunohistochemical staining for the low molecular weight neurofilament subunit (NF-L) was carried out using an NR4 monoclonal antibody. To localize axons exhibiting a regenerative response immunohistochemical staining for the growth associated protein GAP43 was employed. In sham controls, at the light microscopic level NF-L-immunoreactive axonal swellings were numerous at 7 days, but by 14 days post injury their frequency declined markedly. In contrast, GAP43-immunoreactive, disconnected reactive axonal swellings were rarely observed at 7 days but were numerous at 14 days. Ultrastructural analysis at 14 days post injury of carefully matched sections revealed reactive axons demonstrating sprouting consistent with a regenerative effort. Analysis of tissue from animals of 14 days of survival indicated that supplementation with nerve growth factor did not appear to enhance the capacity of damaged brain axons to mount a regenerative attempt. Rather, it appears that regenerative efforts seen reflect a spontaneous response. A third group of adult cats, subjected to the same injury but not subjected to osmotic pump implantation, was allowed to survive for 22-28 days. Animals in this group also demonstrated GAP43 immunoreactivity in reactive axonal swellings in the brain stem. This study demonstrates that diffusely injured axons can mount a sustained regenerative attempt that is associated with a reorganization of their cytoskeleton and accompanied by an up-regulation of growth-associated proteins.

Animals↗

PubMed1994

Reduction in muscarinic receptors by antisense oligodeoxynucleotide.

Treatment of rat superior cervical ganglion cells in culture for 4 days with an antisense oligodeoxynucleotide corresponding to a partial sequence of the mRNA coding the m1 muscarinic receptor decreased m1 receptor mRNA by 64% without affecting m2 receptor mRNA. [3H]Pirenzepine binding to M1 receptors was decreased by 43%. Intraventricular infusion of this antisense oligodeoxynucleotide reduced muscarinic receptor density in M1 but not M2 receptor-rich brain regions.

Animals↗

PubMed1984

Enkephalin-like immunoreactivity in rat area postrema: ultrastructural localization and coexistence with serotonin.

The ultrastructure of enkephalin-containing neurons and their capacity to take-up [3H]serotonin were examined in the area postrema. Untreated adult rats and rats with intraventricular infusions of 10(-4) M tritiated serotonin, 5-hydroxytryptamine [( 3H]5-HT) were perfused with 4% paraformaldehyde and 0.2-0.5% glutaraldehyde. Coronal Vibratome sections through the area postrema from both groups of animals were immunocytochemically labeled with an antiserum to leucine Leu5-enkephalin. The sections from the animals infused with the isotope subsequently were processed for autoradiography. Enkephalin-like immunoreactivity (ELI) was detected in perikarya, dendrites, axons and axon terminals most frequently located along the ventricular and ventrolateral portions of the area postrema. The labeled perikarya were few in number and were characterized by a thin rim of cytoplasm containing peroxidase immunoreactivity. Dendrites and terminals containing ELI formed synapses primarily with unlabeled axon terminals and dendrites, respectively. However, terminals containing ELI also formed synaptic junctions with other unlabeled axon terminals. Appositions between enkephalin-containing processes and modified glia were occasionally seen near the ventricular surface. In sections processed for both immunocytochemistry and autoradiography, approximately 5% of the terminals containing ELI showed uptake of [3H]5-HT. We conclude that neurons containing ELI are primarily, but not exclusively, associated with other intrinsic neurons or afferents in the rat area postrema and that some of the enkephalin-labeled terminals have the capacity to take-up serotonin. Specificity of uptake of [3H]5-HT in neurons containing endogenous serotonin and factors which may contribute to the low probability of detecting both peroxidase and autoradiographic markers in single sections are discussed.

Animals↗

PubMed1987

Serotonin axon terminals in the ventral tegmental area of the rat: fine structure and synaptic input to dopaminergic neurons.

The serotoninergic (5-hydroxytryptamine, 5-HT) innervation of the rat ventral tegmental area (VTA) was examined by light and electron microscopic radioautography following intraventricular infusion of [3H]5-HT. The [3H]5-HT labeled processes were characterized with respect to their regional distribution, ultrastructure and relationships with all neurons, including dopaminergic neurons, identified in the same sections using immunocytochemistry for the localization of the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH). By light microscopy, [3H]5-HT labeled axons and axonal varicosities were detected throughout the interfascicular nucleus and ventral portion of the VTA. By electron microscopy, [3H]5-HT-labeled axons were found to be mainly small and unmyelinated, although a few showed several lamellae of myelin. The labeled varicosities measured 0.6 micron in mean diameter and contained many small, round or flattened agranular vesicles and a few large granular vesicles. More than 18% showed synaptic specializations in single thin sections. Most of these synapses were asymmetric and established on dendritic shafts. Based on the probability of seeing such synaptic specializations in single thin sections, it was estimated that as many as 50% of the labeled 5-HT terminals formed synaptic contacts in the VTA. In dually labeled light microscopic sections, [3H]5-HT-accumulating processes often appeared adjacent to TH-immunoreactive perikarya and proximal dendrites. Electron microscopy demonstrated that terminals with radioautographic labeling for 5-HT formed conventional synapses both with TH-labeled and unlabeled dendrites in the VTA. Many additional 5-HT terminals lacking recognizable synaptic densities were directly apposed to TH-labeled dendrites and were isolated from the rest of the neuropil by thin glial leaflets. These results suggest that 5-HT neurons innervate both dopaminergic and non-dopaminergic neurons in the VTA and may influence mesocortical and mesolimbic efferent systems through synaptic as well as non-synaptic mechanisms.

Animals↗

PubMed1988

Antibodies to ependymin block the sharpening of the regenerating retinotectal projection in goldfish.

The regenerating optic nerve of goldfish first reestablishes a rough retinotopic map on the tectum, then goes through an activity dependent refinement that appears to involve the elimination of inappropriate branches from early regenerated arbors. Retinotopically appropriate branches and synapses may be stabilized because the normally correlated firing of neighboring ganglion cells could cause summation of their postsynaptic responses, making them more effective. Thus, refinement of the map may be similar in several ways to associative learning. In this study, we therefore tested whether ependymin, a major protein component of the extracellular fluid that has been implicated in synaptic changes thought to be associated with learning a simple task in goldfish, may also be involved in refinement of the retinotopic map. Goldfish that had undergone unilateral optic nerve crush received intraventricular infusion of antiependymin IgG or of control IgG's beginning at 21 days postcrush. Tectal recordings from these fish at 39-56 days postcrush showed that the projection had failed to sharpen, much as in the fish with activity blocked or synchronized; the average size of the multiunit receptive fields was 31 degrees vs 11 degrees normally. The field potentials elicited from these tecta by optic nerve shock were not significantly smaller than in controls, suggesting normal levels of synaptogenesis. Control projections, identically treated but infused with either unrelated IgG or Ringer's alone regenerated normally, giving multiunit receptive fields of 12 degrees. Intact (non-regenerating) projections of the experimental fish were not rendered abnormal by the IgG treatment. Histology showed the retinas and tecta of the infused fish to be normal in appearance. The results show a specific block of sharpening by antiependymin IgG. The ependymal glia of the tectum stain positively for ependymin in normal fish, particularly the cell bodies in the ependymal layer. The tectum, particularly the ependymal layer, stains more intensely during regeneration, which appears to trigger increased synthesis of ependymins in the ependymal glia. This increase and the block of sharpening by specific antibodies to ependymin suggest a possible role for ependymin in activity dependent synaptic stabilization, possibly through its polymerization when calcium is focally depleted at active synapses.

Action Potentials↗

PubMed1988

Chronic administration of a thiol-proteinase inhibitor blocks long-term potentiation of synaptic responses.

It has been proposed that activation of a calcium-sensitive protease (calpain) is a crucial step in the induction of long-term potentiation (LTP). To test this hypothesis, we used chronic recording techniques to measure the effects of intraventricular infusion of leupeptin, a calpain inhibitor, on LTP in the hippocampus. Rats implanted bilaterally with stimulating electrodes in the Schaffer-commissural system and one recording electrode in the apical dendrites of field CA1 were fitted with osmotic mini-pumps delivering either leupeptin (20 mg/ml) or saline at a rate of 0.5 microliter/h into the lateral ventricle. Short bursts of high-frequency stimulation with the bursts delivered at 5/s were used to induce LTP in those animals which had stable responses for several days. Rats in the saline group (n = 11) exhibited an immediate LTP effect that remained in place over successive days of testing, while only 3 of 13 leupeptin treated animals showed evidence of LTP 24 h after high-frequency stimulation, and in only one of those was a sizeable effect recorded over several days. The average change in responses at the 24-h test point was +33% for the controls and +4% for the leupeptin group (P less than 0.01). The block of LTP induction was reversible, since high-frequency stimulation applied after disconnecting the pumps led to a robust LTP effect that lasted for several days in 6 of 7 animals tested. There were no detectable differences in baseline responses in the presence and absence of leupeptin.

Animals↗

PubMed1988

Transplantation of norepinephrine neurons into aged rats improves performance of a learned task.

A reproducible behavioral correlate of aging in rodents is deficient performance of inhibitory avoidance memory tasks. Impaired performance has been attributed, in part, to age-related changes in brain norepinephrine (NE) system function. To determine whether supplementation of brain NE can ameliorate avoidance deficits in aged animals, we transplanted noradrenergic locus coeruleus neurons from fetal rat donors into the third cerebral ventricle of 24-month-old male F344 rats. Aged rats that received NE-containing grafts exhibited significant improvement of inhibitory avoidance retention performance compared to both unoperated aged animals and aged animals that received grafts of cerebellar tissue. Improved behavioral performance was prevented by pretreatment of NE graft recipients with the beta-adrenergic receptor blocking agent, propranolol, and was mimicked by chronic intraventricular infusion of NE. Taken together, our findings support the view that age-related declines in brain NE content contribute to age-related deficits in inhibitory avoidance performance, and that NE replacement therapy can improve performance of this task in aged rats.

Aging↗