Cortex Of Old Rats Research Articles

Neuroprotective effects of rosemary extract on white matter of prefrontal cortex in old rats.

During aging, cerebral structures undergo changes due to oxidative stress. The consumption of some plants seems to improve neurological health. For example, rosemary extract (RE) which is widely used as a flavoring food has anti-inflammatory and anti-oxidant activities. Therefore, we aimed to study the effect of RE on the changes related to the aging process in the prefrontal cortex (PFC). Twenty-four male Wistar rats including young and old were purchased. Each group was divided into two subgroups: vehicle and rosemary (old vehicle (OV), old rosemary (OR), young vehicle (YV), and young rosemary (YR) groups). Then, we examined the number of intact neurons, myelin base protein (MBP), white matter (WM), levels of malondialdehyde (MDA), and glutathione peroxidase (GPx) in the PFC. The results showed that in the old vehicle rats compared to the young group without treatment, except for the MDA level (which increased), other variables significantly decreased (P≤0.05). Additionally, RE consumption demonstrated a significant elevation of WMA, MBP intensity, number of intact neurons, and GPx activity level, while MDA levels significantly reduced in the treated old rats compared to the old vehicle group (P≤0.05). However, there was no significant difference between the OR and YV groups (P≥0.05). Overall, it seems that RE can protect and improve aging damages in the PFC due to its anti-oxidant properties. So, the use of RE can be a suitable strategy to prevent aging complications in the brain.

Ethylmethylhydroxypyridine Succinate Limits Stress-Induced Neuroinflammation in the Cerebral Cortex of Old Rats

Ethylmethylhydroxypyridine Succinate Limits Stress-Induced Neuroinflammation in the Cerebral Cortex of Old Rats

Ethylmethylhydroxypyridine Succinate Limits Stress-Induced Neuroinflammation in the Cerebral Cortex of Old Rats

Ethylmethylhydroxypyridine Succinate Limits Stress-Induced Neuroinflammation in the Cerebral Cortex of Old Rats

Age-Related Alterations in Prelimbic Cortical Neuron Arc Expression Vary by Behavioral State and Cortical Layer.

Prefrontal cortical and medial temporal lobe connectivity is critical for higher cognitive functions that decline in older adults. Likewise, these cortical areas are among the first to show anatomical, functional, and biochemical alterations in advanced age. The prelimbic subregion of the prefrontal cortex and the perirhinal cortex of the medial temporal lobe are densely reciprocally connected and well-characterized as undergoing age-related neurobiological changes that correlate with behavioral impairment. Despite this fact, it remains to be determined how changes within these brain regions manifest as alterations in their functional connectivity. In our previous work, we observed an increased probability of age-related dysfunction for perirhinal cortical neurons that projected to the prefrontal cortex in old rats compared to neurons that were not identified as projection neurons. The current study was designed to investigate the extent to which aged prelimbic cortical neurons also had altered patterns of Arc expression during behavior, and if this was more evident in those cells that had long-range projections to the perirhinal cortex. The expression patterns of the immediate-early gene Arc were quantified in behaviorally characterized rats that also received the retrograde tracer cholera toxin B (CTB) in the perirhinal cortex to identify projection neurons to this region. As in our previous work, the current study found that CTB+ cells were more active than those that did not have the tracer. Moreover, there were age-related reductions in prelimbic cortical neuron Arc expression that correlated with a reduced ability of aged rats to multitask. Unlike the perirhinal cortex, however, the age-related reduction in Arc expression was equally likely in CTB+ and CTB− negative cells. Thus, the selective vulnerability of neurons with long-range projections to dysfunction in old age may be a unique feature of the perirhinal cortex. Together, these observations identify a mechanism involving prelimbic-perirhinal cortical circuit disruption in cognitive aging.

High-protein and low-calorie diets improved the anti-aging Klotho protein in the rats\u2019 brain: the toxic role of high-fat diet

BackgroundIn the current study, our specific aim was to characterize the Klotho protein and expression levels in the hippocampus and prefrontal cortex of old rats treated with different diets (high-fat, high-protein, low-calorie, high-protein and low-calorie).MethodsRats were treated with high-fat, high-protein, low-calorie, low-calorie high-protein diets for 10 weeks and then behavioral and molecular assessments were evaluated.ResultsStatistical analysis showed the percentage of open arm time was increased in the high-protein, low-calorie and low-calorie high-protein groups compared with old control (old-C) rats. The percentage of open arm entries was increased in the low-calorie and low-calorie high-protein group compared with old-C rats. The body weight and serum triglyceride were decreased in the low-calorie and low-calorie high-protein groups in comparison to control old rats. Low-calorie and low-calorie high-protein treatments statistically enhanced caspase-3 level compared with old-C rats in the hippocampus and prefrontal cortex. Treatment of old rats with high-protein, low-calorie and low-calorie high-protein could increase Klotho-α level compared with control old rats. The levels of Klotho-α, c-fos and brain-derived neurotrophic factors were decreased in the low-calorie high-protein group in Klotho inhibitor's presence compared with the low-calorie high-protein group.ConclusionAccording to our findings, Klotho-α level was reduced in old rats. Low-calorie, high-protein and particularly low-calorie high-protein diets increased this protein level and consequently increased neuronal plasticity and improved memory function.Graphic abstract

Characteristics of Changes in Lipid Peroxidation and Na+/K+-ATPase Activity in the Cortex of Old Rats in Conditions of Two-Vessel Cerebral Ischemia/Reperfusion

The success of studies on the neuroprotective properties of compounds depends on the used model of diseases of the central nervous system on animals. The approaches widely used to model cerebral ischemia/reperfusion were developed on young animals and may not be as efficient or may not be suitable at all for modeling on old animals, which are recommended for preclinical trials. The goal of the study was to detect age-related features of the effect of cerebral reperfusion of different duration (1 and 3 h) after two-vessel forebrain ischemia on the level of lipid peroxidation (LPO) products and the activity of Na+/K+-ATPase in the cerebral cortex of rats aged 22–24 months. We found a late accumulation (3 h, but not 1 h, after restoration of the blood flow) of LPO products, specifically, triene conjugates and Schiff bases, and a decrease in Na+/K+-ATPase activity in the cerebral cortex of old rats as compared with young animals. This indicates the features of the molecular and physiological mechanisms of the development of disorders in the brain during ischemia/reperfusion in old and young animals. It is necessary to take into account the identified differences in these mechanisms in the development and testing of compounds that will be subsequently used for the treatment of elderly patients with stroke and ischemic brain damage.

The effect of vascular peptide bioregulator on microcirculation in the brain cortex of old rats

Using a TV device to study brain microcirculation, we found that after a course of vascular peptide bioregulator the density of microvascular network of pia matter of old rats (22-24 months) sensomotor cortex increased about 2,5-2,8 times compared to control old rates; and noradrenaline-induced constriction reactions and acetylcholine-induced dilative reactions of the pial arterioles increased significantly. This perfusion in the tissue of the cerebral cortex is not increased, but the degree of blood oxygen saturation in the microvasculature of this tissue region raised.

Abstract 481: Age-related Hypertension and Salt-sensitivity Are Associated With Specific Kidney Cortico-medullary Distribtion of D1R, AT1R And NADPH-oxidase

We recently reported that oxidative stress has a causal role in increasing kidney angiotensin II AT1 receptor (AT1R) and decreasing dopamine D1 receptor (D1R) functions in the aging Fischer Brown Norway (FBN) rats. These renal receptors by counter-regulating each other’s functions maintain sodium homeostasis and normal blood pressure (BP). Here, we examined systolic BP and kidney distribution (cortex vs medulla) of these receptors as well as of an oxidant producing enzyme (gp 91phox -NADPH-oxidase) in response to 4-week normal-salt (NS, 0.4% NaCl) and high-salt (HS, 8% NaCl) feeding in adult (3-month) and old (21-month) FBNs. BP in conscious animals was measured by radio-telemetry. Distribution of D1R, AT1R and gp 91phox were determined by RT-PCR and western blotting. We found that NS-fed old rats had higher BP (adult vs old: 105±1 vs 118 ±1 mmHg), which further increased with HS feeding in these rats (adult vs old: 111±1 vs 124 ±1 mmHg). The levels of D1R mRNA in cortex or in medulla were not different between NS-fed adult and old rats, but decreased in both cortex [adult vs old: 67 ± 15 vs 54±16 density unit (DU)] and medulla (adult vs old: 22±15 vs 11±3 DU) only in HS-fed old rats. Contrary to this, AT1R mRNA levels were higher only in cortex of old rats fed either NS (adult vs old: 81 ± 23 vs 102± 34 DU) or HS (adult vs old: 80 ± 17vs 98 ± 36 DU). Moreover, there were similar gp 91phox mRNA levels in the cortex and medulla of adult and old rats fed either NS or HS. But, its protein levels were higher in the cortex of old rats fed NS (adult vs old: 60±7 vs 112±8 DU) and HS (adult vs old: 61±3 vs 94±15 DU), and increased only in the medulla with HS feeding in these rats (adult vs old: 12±1 vs 28±2 DU). Our results suggest that there exists a specific cortico-medullary expression pattern of D1R, AT1R and gp 91phox with NS and HS feeding in old rats, which might be contributing to age-related hypertension and salt-sensitivity in FBNs.

Metabonomic alterations in hippocampus, temporal and prefrontal cortex with age in rats

The metabolic changes in hippocampus, temporal cortex and prefrontal cortex in SD rats along with aging were explored using a metabonomic approach, which based on high resolution “magic angle spinning” 1H NMR spectroscopy. The metabolite profiles were analyzed by partial least squares-discriminant analysis, and the results showed that the metabolites of the above three brain regions in old rats were dramatically different from that in the adult and young rats. The old rats showed increased myo-inositol and lactate in all of the three brain regions, and decreased N-acetylaspartate in temporal and frontal cortex, Glutamate–GABA level became imbalance in temporal cortex of old rats. In addition, compared with the adult female rats, male rats had higher levels of N-acetylaspartate, taurine, and creatine in temporal or frontal cortex. The age-related metabolic changes may indicate the early functional alterations of neural cells in these brain regions, especially the temporal cortex. The gender-related metabolic changes suggest the significance of the hormonal regulation in brain metabolism. Our work highlights the potential of metabolic profiling to enhance our understanding of biological mechanisms of brain aging.

Decreased NHE8 isoform expression and defective acidification in proximal convoluted tubules of senile rats

We have previously found that aged rats show decreased proximal acidification without changes in NHE3 or V-H(+) ATPase expression in brush border membrane vesicles. However, we did not identify any mechanism underlying these observations. The aim of the present work was to evaluate some of the regulatory systems of proximal acidification that could be affected by aging. We measured plasma concentrations of parathyroid hormone (PTH) and the amount of cAMP in the renal cortex of young and old Wistar rats. PTH plasma concentration was increased in old rats, whereas, although it showed a tendency to increase, the cAMP content in the renal cortex of old rats was not significantly different compared with the cortex of young rats. We measured the abundance of NHE8 isoforms of the Na(+)/H(+) exchanger in brush border membrane vesicles from proximal convoluted tubules (PCT) of young and old rats by western blot analysis. We performed RT-PCR experiments in renal cortex homogenates from both experimental groups to evaluate mRNA expression of NHE3, NHE8 and H(+)ATPase. In senile rats, we detected a decreased abundance (at both gene expression and protein level) of the NHE8 isoform. These results could explain previous observations in which proximal tubule acidification appears affected in aged rats through a decrease in the activity of ethylisopropyl amiloride (EIPA)- and Bafilomycin-sensitive components, without changes in the NHE3 and V-H(+)ATPase abundance in the apical membrane of the PCT.

Aging increases Oxidative Stress and Renal Expression of Oxidant and Antioxidant Enzymes that Are Associated with an Increased Trend in Systolic Blood Pressure

The aim of this study was to investigate whether the effects of aging on oxidative stress markers and expression of major oxidant and antioxidant enzymes associate with impairment of renal function and increases in blood pressure. To explore this, we determined age-associated changes in lipid peroxidation (urinary malondialdehyde), plasma and urinary hydrogen peroxide (H(2)O(2)) levels, as well as renal H(2)O(2) production, and the expression of oxidant and antioxidant enzymes in young (13 weeks) and old (52 weeks) male Wistar Kyoto (WKY) rats. Urinary lipid peroxidation levels and H(2)O(2) production by the renal cortex and medulla of old rats were higher than their young counterparts. This was accompanied by overexpression of NADPH oxidase components Nox4 and p22(phox) in the renal cortex of old rats. Similarly, expression of superoxide dismutase (SOD) isoforms 2 and 3 and catalase were increased in the renal cortex from old rats. Renal function parameters (creatinine clearance and fractional excretion of sodium), diastolic blood pressure and heart rate were not affected by aging, although slight increases in systolic blood pressure were observed during this 52-week period. It is concluded that overexpression of renal Nox4 and p22(phox) and the increases in renal H(2)O(2) levels in aged WKY does not associate with renal functional impairment or marked increases in blood pressure. It is hypothesized that lack of oxidative stress-associated effects in aged WKY rats may result from increases in antioxidant defenses that counteract the damaging effects of H(2)O(2).

Structural Synaptic Remodeling in the Perirhinal Cortex of Adult and Old Rats Following Object-Recognition Visual Training

The ultrastructural features of layer II synapses in the perirhinal cortex of adult (4- to 6-month-old) and old (25- to 27-month-old) rats exposed to a six-session object recognition visual training were investigated by morphometric methods. The comparative analysis showed a higher synaptic numeric density, a lower synaptic average area, and a lower percentage of megasynapses (S > 0.5 microm2) in old trained rats versus controls, and a higher percentage of small (S < 0.15 microm2) junctions in adult trained rats versus controls. The more marked synaptic remodeling underlying memory consolidation in the perirhinal cortex of old rats might reflect a pre-existing lower dynamic status.

Effects of age on reserpine-induced orofacial dyskinesia and possible protection of diphenyl diselenide

Acute reserpine administration produces persistent oral dyskinesia in rats, an alleged animal model of tardive dyskinesia. The pathophysiology of the syndrome remains unclear, but experimental evidence suggests that neurodegeneration in the basal ganglia caused by oxidative stress plays a pivotal role in TD development. In this paper, the authors examined whether diphenyl diselenide, an organochalcogen with antioxidant properties, changes the behavioral and neurochemical effect of acute reserpine administration in old rats. The basal vacuous chewing movements (VCMs) and facial twitching (FT) duration was higher in old rats (15 months of age), when compared with adult rats (3 months of age; 0.01). Basal thiobarbituric acid-reactive species (TBARS) levels were increased only in the cortex of old rats, when compared to adult animals ( p < .05). Reserpine injection (1 mg/kg, s.c. for 3 days every other day) caused a significant increase on the tongue protusion (TP) frequency ( p < .01) and facial twitching duration ( p < .01) in old rats. Diphenyl diselenide (10 mg/kg, i.p. for 4 days, starting the day before reserpine) reversed only reserpine-induced TP increase ( p < .01). Reserpine caused a significant increase in striatal TBARS levels ( p < .01) and diselenide reversed ( p < .01) the effect of reserpine on TBARS levels in the striatum. In subcortical parts, isolated reserpine or diselenide administration significantly increased ( p < .01) the levels of TBARS, while simultaneous treatment with reserpine and diselenide reverted this effect ( p < .01). The results of the present study confirmed the effects of age on orofacial dyskinesia. Diphenyl diselenide, an organochalcogen with antioxidant properties, showed modest effects on reserpine-induced orofacial dyskinesia. However, additional studies are still necessary to establish whether this compound can be considered an effective antioxidant in other models of neurotoxicity.

Apoptosis induction by phencyclidine in the brains of rats of different ages

We examined whether acute administration of phencyclidine (PCP), an antagonist of the N-methyl-D-aspartate (NMDA) receptor-channel complex, can cause neuronal toxicity that is associated with apoptosis. Three- and 24-month-old rats were placed in locomotor activity chambers. PCP (50 mg/kg) or saline (0.15 M NaCl) were simultaneously administered to the treated and age-matched controls. After observing changes of locomotor activities, the animals were killed 24 h after treatment. The brains were processed for in situ analysis of apoptosis either by propidium iodide (PI) staining, or for the terminal dUTP nick-end labelling (TUNEL) method. The regional distribution of apoptotic nuclei was established using PI staining. Apoptosis was additionally confirmed and quantified by the TUNEL technique. PI and TUNEL staining revealed that PCP-mediated neurotoxicity in the prefrontal and enthorhinal cortices, the striatum and hippocampus was associated with a significant number of neurons exhibiting apoptotic morphology. We found that the total number of apoptotic cells was higher in the brains of 24-month-old rats. Compared to the respective controls the number of apoptotic cells was 3.8-fold greater in the cortex of old rats, followed by the striatum (three-fold), and hippocampus (1.4-fold). Accordingly, we concluded that ageing was accompanied by DNA-damage that was most pronounced in the prefrontal cortical neurones. The most prominent elevation in the degree of apoptosis in the young-treated compared to young-untreated rats was detected in the striatum. Comparison of the number of TUNEL-positive cells in treated-aged versus treated-young rats revealed that in all the examined regions of the brain PCP exerted a stronger apoptotic effect in younger animals.

Effects of Taurine on Ozone-Induced Memory Deficits and Lipid Peroxidation Levels in Brains of Young, Mature, and Old Rats

To determine the antioxidant effects of taurine on changes in memory and lipid peroxidation levels in brain caused by exposure to ozone, we carried out two experiments. In the first experiment, 150 rats were separated into three experimental blocks (young, mature, and old) with five groups each and received one of the following treatments: control, taurine, ozone, taurine before ozone, and taurine after ozone. Ozone exposure was 0.7–0.8 ppm for 4 h and taurine was administered ip at 43 mg/kg, after or before ozone exposure. Subsequently, rats were tested in passive avoidance conditioning. In the second experiment, samples from frontal cortex, hippocampus, striatum, and cerebellum were obtained from 60 rats (young and old), using the same treatments with 1 ppm ozone. Results show both an impairment in short-term and long-term memory with ozone and an improvement with taurine after ozone exposure, depending on age. In contrast to young rats, old rats showed peroxidation in all control groups and an improvement in memory with taurine. When taurine was applied before ozone, we found high peroxidation levels in the frontal cortex of old rats and the hippocampus of young rats; in the striatum, peroxidation caused by ozone was blocked when taurine was applied either before or after ozone exposure.

Aging, high salt intake, and renal dopaminergic activity in Fischer 344 rats.

The present study examined renal dopaminergic activity and its response to high salt (HS) intake in adult (6-month-old) and old (24-month-old) Fischer 344 rats. Daily urinary excretion of L-3, 4-dihydroxyphenylalanine (L-DOPA), dopamine, and its metabolites 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid was similar in adult and old rats; by contrast, daily urinary excretion of norepinephrine in old rats was almost twice that in adult animals. HS intake (1% NaCl) over a period of 24 hours resulted in a 2-fold increase in the urinary excretion of dopamine, DOPAC, and norepinephrine in adult animals but not in old animals. Norepinephrine and L-DOPA plasma levels did not change during HS intake and were similar in both groups of rats. The natriuretic response to an HS intake in old rats (from 4.7+/-0.4 to 10.7+/-2.0 nmol. kg(-1). d(-1); Delta=6.0+/-0.9 nmol. kg(-1). d(-1)) was less than in adult rats (from 5.2+/-0.4 to 13.5+/-2.5 nmol. kg(-1). d(-1); Delta=8.3+/-0.8 nmol. kg(-1). d(-1)). A diuretic response to HS intake was observed in adult rats (from 20.9+/-2.3 to 37.6+/-2.8 mL. kg(-1). d(-1)) but not in old rats (from 37.7+/-5.7 to 42.3+/-6. 0 mL. kg(-1). d(-1)). Dopamine levels and dopamine/L-DOPA ratios in the renal cortex of old rats were greater than in adult rats. HS intake increased both dopamine levels and dopamine/L-DOPA ratios in the renal cortex of adult rats but not in old rats. Aromatic L-amino acid decarboxylase activity was higher in old rats than in adult rats; HS intake increased L-amino acid decarboxylase activity (nmol. mg protein(-1). l5 min(-1)) in adult rats (from 67+/-1 to 93+/-1) but not in old rats (from 86+/-2 to 87+/-2). Dopamine inhibited Na(+),K(+)-ATPase activity in proximal tubules obtained from adult rats, but it failed to exert such an inhibitory effect in old rats. It is concluded that renal dopaminergic tonus in old rats is higher than in adult rats but fails to respond to HS intake as observed in adult rats. This may be due in part to the inability of dopamine to inhibit Na(+),K(+)-ATPase activity in old rats.

Insulin-like growth factor-1 stimulation of protein synthesis is attenuated in cerebral cortex of aging rats

It has been postulated that brain aging and the accompanying neurodegenerative processes associated with aging result from a deterioration of mechanisms that regulate the maintenance of basic cellular processes. In the present study, it was hypothesized that decreased availability and/or diminished responsiveness of tissues to growth factors such as insulin-like growth factor-1 may be partly responsible for decreases in total protein synthesis previously observed in aging animals. Male Brown Norway rats (5-7 and 27-28 months old) were used to determine (1) whether in vivo protein synthesis in cortex, hippocampus, hypothalamus and cerebellum decreases with age and (2) whether these deficiencies are associated with age-related alterations in response to insulin-like growth factor-1, des (1-3) IGF-1 or insulin. Analysis of in vivo protein synthesis rates revealed a decline of 20% in cortex of old rats (P < 0.05) but no changes were observed in hippocampus, hypothalamus, or cerebellum. Stimulation of cortical slices in vitro with insulin-like growth factor-1, des (1-3) insulin-like growth factor-1, or insulin increased protein synthesis rates in young animals, but the response to these growth factors was blunted in old animals. Analysis of type 1 insulin-like growth factor receptor densities by quantitative autoradiography demonstrated age-related decreases in receptor levels in cerebellar cortex and dentate gyrus of the hippocampus but no changes in cortex. Regional distribution of type 1 insulin-like growth factor receptors within each of these tissues did not appear to change with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of neurofilament proteins in the rat cerebellar cortex as a function of age: an immunohistochemical study

The present study was designed to assess changes in the expression of cytoskeletal proteins in the cerebellar cortex of rats of different ages using immunohistochemical techniques associated with image analysis. Male Wistar rats of 3 months (young), 12 months (adult) and 24 months (old) were used. Neuronal cytoskeleton was investigated using monoclonal antibodies to phosphorylated neurofilament (NF) proteins of high (H), medium (M) and low+H+M molecular weight (NF triplet). In young and adult rats in which the expression of phosphorylated NF immunostaining was similar, a dark-brown immunoreactivity was observed primarily in axons of the white matter and of basket neurons which surround Purkinje neurons and enter in the molecular layer. In adult rats a NF-H immunoreactivity was sometimes observed within the dendritic tree of Purkinje neurons. A significant decrease in the density of NF immunoreactivity involving the three different subunits investigated was found in the cerebellar cortex of old rats. This suggests that cytoskeletal abnormalities occur not only in senile dementia, but also in the so called ‘physiological aging’. The cerebellar cortex may represent an interesting model for evaluating age-dependent changes of cytoskeleton.

Brain cholinergic enzymes and cortical EEG activity in young and old rats

1. Cholinergic enzymes (ChAT, AChE) in different areas of the brain and cortical electroen cephalography (EEG) activity were investigated in young and old rats. 2. In old rats, ChAT activity was low in the striatum, but high in the amygdala. Compared to young rats, ChAT activity in old rats was unchanged in the frontal, parietal/occipital and entorhinal cortex as well as in the hypothalamus, midbrain, hippocampus and brain stem. 3. AChE activity in old rats was lower than in young animals in the parietal/occipital cortex, hippocampus, striatum and brainstem. In other areas of the brain AChE activity was unchanged. 4. In old rats the peak frequency (Fp) of cortical EEG activity (mobility-related) was significantly lower than in young animals, both frontally and occipitally. The power of 5–10 Hz frequency band was markedly lower than in young rats. During immobility, the power of the 1.5–3 Hz and 3–5 Hz bands was lower in the frontal cortex of old rats. The power of 3–5 Hz, 5–10 Hz and 10–20 Hz bands was lower in the occipital cortex of old rats. In all of the old rats, but not in any of the young ones, symmetric high voltage activity was observed in the frontal pole of the cortex. 5. These results suggest that the age-related decrease of higher frequencies of cortical EEG activity may be related to the decrease of AChE activity in the parietal/occipital cortex. This decrease in AChE may reflect degeneration of the cholinergic synapses.

Age‐Related Changes in Rat Serotonergic and Adrenergic Systems and in Receptor Responsiveness to Subchronic Desipramine Treatment

Noradrenergic (NA) and serotonergic (5-HT) receptor profiles were compared in the cerebral cortex of young adult (3 months old) and aged (24 months old) male Sprague Dawley rats. Beta and alpha-1 receptors were significantly decreased in 24 month old rats, whereas alpha-2 receptors remained unchanged. 5-HT-2 Postsynaptic receptors and 5-HT high affinity uptake were reduced in aged animals; on the other hand the number of 3H-imipramine (3H-IMI) recognition sites located on serotonin nerve terminals and labelled also by 3H-paroxetine (3H-PAR), were significantly higher in the cerebral cortex of old rats. The ratio 5-hydroxyindoleacetic acid (5-HIAA)/5-HT, an index of serotonin turn-over, increased in some brain areas of senescent rats. There were no age-related changes in the responsiveness of investigated binding sites to subchronic desipramine treatment; the density of beta-noradrenergic and 5-HT-2 serotonergic receptors and that of 3H-IMI binding sites was reduced both in young adult and aged rats.