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Biomedical subjects

L Angelucci

Publications and source records attributed to L Angelucci.

At least 91 records · Page 5Linked to original sources

Strain-dependent differences in hippocampal glucocorticoid binding capacity and active avoidance in the mouse.

Maximal individual [3H]corticosterone binding capacity in the hippocampus was lower in C57BL/6 mice than in BALB/c mice, and positively correlated with active avoidance learning in the two strains. Moreover, a parallel difference in the activity of hypothalamo-pituitary adrenocortical axis (HPAA) was found, consisting in a level of plasma corticosterone in C57BL/6 higher than in BALB/c mice. These results confirm the genetically determined differences in behavior of C57BL/6 and BALB/c mice, and demonstrate their association with differences in hippocampal corticosterone binding capacity, pointing to a functional relationship between the behavioral and neuroendocrine parameters.

Animals↗

Stress activation of limbic and cortical dopamine release is prevented by ICS 205-930 but not by diazepam.

Systemic administration of the 5-HT3 receptor antagonist ICS 205-930, but not of the benzodiazepine diazepam, was able to prevent the stimulation of dopamine release in the nucleus accumbens and prefrontal cortex induced by restraint stress. These findings suggest that stress is not simply co-extensive with anxiety and that 5-HT3 receptors could regulate the dopaminergic response to stress.

Animals↗

125I-beta-nerve growth factor binding is reduced in rat brain after stress exposure.

In the central nervous system (CNS), the presence of nerve growth factor (NGF) and its receptor, NGFR, in cholinergic neurons has been demonstrated. In this study we report that, after exposure to stress, there was a reduction in total binding of NGF in the hippocampus and basal forebrain of 3.5-month-old rats without significant changes in the frontal cortex or cerebellum. Chronic treatment with acetyl-l-carnitine (ALCAR), that prevents some age-related impairments of CNS, for 1.5 months, decreased NGF binding in hippocampus and basal forebrain but abolished the stress-related reduction of NGF binding observed in the hippocampus of untreated rats.

Animals↗

Age-dependent deficits in radial maze performance in the rat: effect of chronic treatment with acetyl-L-carnitine.

1. An eight-arm radial maze was the experimental model used to investigate spatial learning in rats of different ages and in old rats treated with Acetyl-L-Carnitine. 2. Extramaze visual cues were minimized in order to study the rat's ability to perform using a strategy. 3. The experimental findings indicated a deterioration of the old rat's ability to learn and solve the radial maze. 4. Long-term treatment (8 months) with Acetyl-L-Carnitine was found to antagonize such a deterioration.

Acetylcarnitine↗

Aging and immune response: a multivariate approach.

This study on the immune response was chosen as the experimental milieu for the aging process. Parameters associated with the immune response were measured in rats of different ages, thus providing multivariate conditions within which multidimensional data analysis procedures could be applied. These methods, specifically designed for analyzing complex situations, allowed for the delineation of some structural characteristics of maturity and senescence.

Aging↗

Levels of carnitines in brain and other tissues of rats of different ages: effect of acetyl-L-carnitine administration.

Male Sprague-Dawley rats, aged 2, 5, 16, 20 and 30 months and normally fed, were used for determination of carnitines in the brain, serum, heart, tibial muscle, liver and urine. With respect to 5-month-old animals, those aged 30 months exhibited a statistically significant decrement of total carnitine levels in the brain, serum, heart and tibial muscle, accompanied by a dramatic increment in the liver. This suggests impaired net transport of carnitines from the liver to the blood in old age. Urinary excretion was similar in the two age groups. One group received from 5 months on daily 75 mg/kg acetyl-L-carnitine in drinking water. At 20 months, the treated animals showed levels of brain, heart and serum carnitines similar to those of 5-month-old animals. The recovery of brain, heart and serum carnitines in the old animals treated with acetyl-L-carnitine indicates that intestinal absorption and tissue uptake remain sufficiently efficient in the course of aging. The lower level of brain lipofuscins due to acetyl-L-carnitine treatment may be related to the effect of the compound on acetylcholine metabolism.

Age Factors↗

Age-related changes in hypothalamo-pituitary-adrenocortical axis activity in the rat. In vitro studies.

In the aged rat, the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis was found to be increased. In fact, the plasma corticosterone concentrations in the aged (25 months) Sprague-Dawley rat were higher than in the young (3 months) Sprague-Dawley rat. To determine which component of the HPA axis principally contributes to this hyperactivity, an in vitro approach was applied. Neither the adrenal nor the pituitary revealed any age-induced modification in their basal or hormone-stimulated in vitro activity. Moreover, the ability of corticosterone to inhibit the in vitro stimulated pituitary adrenocorticotropic hormone release was preserved in aged rats. On the contrary, the in vitro hypothalamic activity was altered in aged rats. The basal and stimulated release of bioactive corticotropin-releasing factor were increased in aged rats. The results obtained in this study indicate that the hypercorticosteronemia of the aged Sprague-Dawley rat is associated with hypothalamic hyperactivity and with normal in vitro activity and reactivity of the adrenal and pituitary.

Adrenal Cortex↗

Mechanisms in the control of stress responsiveness.

Evidence is given of cooperation between pituitary desensitization to the stimulatory action of corticotropin-releasing hormone (CRH) and glucocorticoid negative feedback in the modulation of the stress responsiveness. With regard to the former, we show that the pituitary becomes unresponsive to repeated CRH administration as soon as 15 min after the first one, while the adrenocortical effect of arginine-vasopressin (AVP) during this period is amplified, suggesting the involvement of AVP in the mechanism that permits repeated pituitary-adrenocortical axis activations. The activation of this axis is blocked by the glucocorticoid negative feedback induced by a previous stress. In fact, after a cold stress (4-6 degrees C for 90 min), the responsiveness to a subsequent psychic stressor (but not to a somatic one) is suppressed. Results after neurotoxic lesion of hippocampal and hypothalamic serotoninergic innervations, would indicate that the neurotransmitter is in some way involved in the accomplishment of this phenomenon.

Animals↗

Nerve growth factor activity and aging in CNS.

This is a discussion of aging in CNS and the influence of the nerve growth factor (NGF) protein. The paper considers neuronal plasticity and neuronotrophic substances, neuronal cell death and the nerve growth factor protein, including its effects, receptors, and model systems for the study of CNS aging.

Aging↗

Acetyl-L-carnitine enhances acetylcholine release in the striatum and hippocampus of awake freely moving rats.

The effect of acetyl-L-carnitine (ALC) on the spontaneous release of acetylcholine (ACh) in the striatum and hippocampus of freely moving rats was investigated using brain microdialysis coupled with HPLC-electrochemical detection. Systemic administration of ALC, in a dose-dependent manner, stimulated ACh release in both areas, while the D-enantiomer was substantially ineffective. The effect of ALC was strongly Ca2+ dependent and tetrodotoxin (TTX) sensitive. These features of an exocytotic and impulse flow-dependent mechanism suggest that the increase in ACh release is the result of ALC activation of a physiological mechanism in cholinergic neurons.

Acetylcarnitine↗

Adrenocorticoid receptor binding in the rat hippocampus: strain-dependent covariations with arousal and habituation to novelty.

In order to investigate whether the genotype-dependent behaviour of the Naples high-(NHE) and low-excitability (NLE) rat strains was modulated by differences in the capacity of hippocampal adrenocorticoid receptors, a correlative analysis was made among behavioural scores from exposure to a Làt-maze and in vitro [3H]corticosterone hippocampal binding capacity in these rats and in their random-bred controls (NRB). As previously shown, NHE/NLE-rats differed markedly upon forced exposure to the maze, with the NRB group occupying an intermediate position. No differences were found in maximal binding capacity (Bmax) and dissociation constant (Kd), nor in the individual maximal binding capacity (IMBC) between the two strains, while both showed lower IMBC than NRB-rats. These results tend to exclude that the genetic differences in the behaviour of NHE/NLE-rats are due to distinct patterns in the adrenocorticoid binding capacity in the hippocampus (HPC). Moreover, the intrastrain correlative analysis among IMBC (in the whole HPC and in its dorsal and ventral portion) and the behavioural scores showed that (1) motor and emotional correlates of 'arousal' to novelty were positively correlated in NLE and negatively in NHE-, but not in NRB-rats; (2) a consistent correlation was found with the intertrial activity decrement (long-term habituation), which was negative in both strains, and it was positive in NRB-rats. These complex co-variations are envisioned as possibly due to the differential modulatory components of the activation and inhibition of novelty-induced arousal response. However, our findings support the hypothesized involvement of the HPC, where adrenocorticoid receptors are selectively concentrated, in the modulation of some adaptive behavioural responses.

Animals↗

5-HT3 receptors control dopamine release in the nucleus accumbens of freely moving rats.

ICS 205-930, a selective and potent 5-HT3 receptor antagonist applied either systemically, or locally into the ventral tegmental area, antagonized the stimulation of dopamine release in the nucleus accumbens, induced by the subcutaneous administration of morphine. These findings, obtained by the use of brain microdialysis in awake freely-moving rats, demonstrate in vivo a functional role of 5-HT3 receptors in the brain. Since stimulation of dopamine release in the nucleus accumbens is a prerequisite for the expression of the rewarding properties of morphine, its suppression by ICS 205-930 suggests a possible application of 5-HT3 receptor antagonists in the treatment of addiction.

Animals↗

Acetyl-L-carnitine reduces the age-dependent loss of glucocorticoid receptors in the rat hippocampus: an autoradiographic study.

Brain autoradiography in adrenalectomized rats injected with 3H-corticosterone 2 hr before sacrifice was used to study the effect of aging and long-term acetyl-l-carnitine treatment on the hippocampal glucocorticoid receptor. Densitometric analysis of silver grains in individual nerve cells of the hippocampus showed that pyramidal neurones of the CA1 field and granular cells of the dentate gyrus are richest in 3H-corticosterone binding sites, whereas pyramidal neurons of the CA3 field have the lowest number of binding sites. There was a significant decline in the number of glucocorticoid receptors within the various hippocampal areas, both as the total number of 3H-corticosterone binding sites and as the number per single pyramidal or granule neuron associated with aging and perhaps due to loss of adrenocorticoid-competent neurons. The dentate gyrus and the CA1 region were mostly affected by the age-dependent decrease in glucocorticoid receptors of the hippocampus. Twenty-eight-month-old rats, treated with acetyl-l-carnitine for 7 months, showed a significantly higher number of 3H-corticosterone binding sites within the various hippocampal regions examined than did age-matched controls. The CA1 and the dentate gyrus were the regions most susceptible to amelioration by acetyl-l-carnitine treatment. These findings suggest a positive effect of acetyl-l-carnitine treatment on age-related changes which occur in the hippocampus.

Acetylcarnitine↗

Maternal adrenalectomy and adult offspring in a conflict situation in the rat.

The effects of the absence of maternal adrenals during pregnancy (P), during lactation (L), during pregnancy and lactation (PL) were studied on pain suppressed behavior (punished drinking test) of the adult offspring in comparison with controls (C). The female L offspring showed a lower responsiveness to the anxiogenic stimulus, as demonstrated by increased water intake, decreased percentage of ineffective licks, and decreased time to perform 300 licks compared to C. The male L behavior was not affected. Reduced growth was not responsible for the reduced anxiogenic reactivity because also both male and female PL offspring had lower weight than C, but did not show any significant effect. Pain threshold in the tail flick test was the same in all types of offspring. Thus, absence of maternal adrenals, specifically during lactation, significantly affects behavior of female offspring. It is discussed whether this is due to the lack of a physiological influence of maternal adrenal hormones on brain ontogenesis (hippocampal glucocorticoid receptors), or on the development of the brain-pituitary-adrenal system during neonatal life of the offspring.

Adrenalectomy↗

Long-term acetyl-L-carnitine preserves spatial learning in the senescent rat.

1. Untreated rats of different ages and old rats chronically treated with Acetyl-1-carnitine were subjected to the spatial learning task. 2. For this test, a circular pool filled with milk-opacified water was used. The animals were to reach an escape platform with the aid of visible environmental cues. 3. The experimental results indicated a clear-cut deterioration of the old animal's acquisition ability of a spatial learning task. 4. The long-term treatment (8 months) with Acetyl-1-carnitine was found to antagonize such a deterioration.

Acetylcarnitine↗

Adenosine and pituitary-adrenocortical axis activity in the rat.

As shown by an increase in plasma corticosterone concentrations, adenosine administration stimulated pituitary-adrenocortical activity. This effect was prevented by dexamethasone (2 mg/kg i.p.). Added in vitro, adenosine reduced both adrenal basal and adrenocorticotropic hormone (ACTH)-stimulated corticosterone release, while it stimulated pituitary ACTH release. This ACTH response was blocked by dexamethasone but not by Tyr-somatostatin. Restraint stress increased adenosine content in the anterior pituitary, suggesting its possible involvement in hormonal stress response. Because the effect of adenosine on plasma corticosterone was still present in rats with a pharmacological block of the endogenous corticotropin-releasing factor release, we propose that adenosine is involved in the regulation of adrenocortical secretion at the level of the anterior pituitary and that this role is exerted through an interaction with a stimulatory adenosine receptor.

Adenosine↗

The effects of clozapine and fluperlapine on the in vivo release and metabolism of dopamine in the striatum and in the prefrontal cortex of freely moving rats.

The effects of the two atypical neuroleptics clozapine and fluperlapine on the dopaminergic function in the striatum and in the prefrontal cortex were studied using the transversal microdialysis technique in awake, freely moving rats. Although neither drug induced catalepsy in rats, both increased the release of dopamine (DA) and the output of its metabolites in a similar way in both areas. Unlike classical neuroleptics, after clozapine and fluperlapine administration, the stimulation of DA release was strictly coupled to that of the metabolites, and a second injection was able to renew it. Pretreatment with the selective D1 agonists SKF 38393 or CY 208-243, by themselves ineffective on the release of DA, antagonized the effects of low doses and substantially reduced those of higher doses of clozapine and fluperlapine, indicating that these two atypical drugs act, depending on the dose, selectively or partially through D1 receptors.

Animals↗