Cortical and limbic dopamine and acetylcholine release as neurochemical correlates of emotional arousal in both aversive and non-aversive environmental changes.
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Acetylcholine↗
Biomedical subjects
L Angelucci
Publications and source records attributed to L Angelucci.
Maternal plasma and milk free cortisol during the first 3 days of breast-feeding following spontaneous delivery or elective cesarean section.
In a view of the increased clinical interest in the presence of hormones in human milk, the objective of this study was to evaluate maternal plasma and milk cortisol levels in early puerperium and their relationship in breast-feeding in women who underwent elective cesarean section or who delivered vaginally. During the first 3 days of breast-feeding, plasma and milk cortisol levels declined significantly both in women who underwent elective cesarean section and in women who had spontaneous deliveries. Moreover, the breast-feeding procedure did not affect maternal plasma and milk hormonal levels, since no differences between the cortisol levels measured immediately before and after morning daily breast-feeding were detected. Furthermore, a very high positive correlation (p < 0.001) was found between plasma and milk cortisol concentrations. Therefore, maternal plasma cortisol levels can be considered a very reliable measure to predict the hormonal concentration in breast milk.
Adult↗
Morphological and electrophysiological changes of peripheral nerve-muscle unit in the aged rat prevented by levocarnitine acetyl.
The effects of levocarnitine acetyl on structure and function of the sciatic nerve and neuromuscular junctions of the soleus and extensor digitorum longus muscles were studied in the aged rat. To that end, neuromuscular conduction velocity (NMCV) was measured in vivo and morphological and morphometric evaluations were performed. Treatment with levocarnitine acetyl, 150 mg/kg day for six months, restored NMCV values to the levels measured in the young rat; significantly reduced the number of degenerating elements; and increased the number of myelinated fibres having normal structural features. In the soleus and extensor digitorum longus muscles, levocarnitine acetyl increased the complexity of neuromuscular junctions. These experimental findings suggest a neurotrophic action of levocarnitine acetyl on the peripheral nervous system that might have therapeutical applications in age-related peripheral nerve changes.
Acetylcarnitine↗
Levocarnitine acetyl stimulates peripheral nerve regeneration and neuromuscular junction remodelling following sciatic nerve injury.
The effects of levocarnitine acetyl were investigated on both peripheral nerve regeneration and neuromuscular remodelling in male Sprague-Dawley rats, three months of age, following crush of their left sciatic nerve. Levocarnitine acetyl, 150 mg/kg/day in drinking water, was given from one week before to 5, 15, 20, and 60 days after nerve crush. The sciatic nerve was examined morphologically at all given times and morphometrically at 15, 20, and 60 days after the lesion. Morphology, at 5, 15, and 60 days, and morphometry, at 60 days after the nerve crush, were also performed on the neuromuscular junction in the soleus and extensor digitorum longus muscles. Five days after nerve crush, complete axonal degeneration was observed in both control and treated rats. At 15 and 20 days, recovery from injury in treated animals was better than in controls, as shown by a significantly higher increase in the number of regenerating axons. At the same times, denervated endplates were present in both groups. At 60 days, axonal regeneration restored the number of axons to normal values in all injured animals, while their size maturation was greater in treated rats than in controls. A markedly lower number of degenerating elements was found in treated animals. In the neuromuscular junctions of the soleus and extensor digitorum longus muscles, nerve terminal branch points were reduced in the lesioned rats in comparison with uninjured ones. However, morphometric analysis revealed a greater endplate complexity in treated animals in which, at 60 days after nerve crush, nerve terminal branching and sprouting index values were significantly higher than in controls. It is concluded that levocarnitine acetyl exerts a beneficial effect on nerve regeneration processes and synaptic remodelling in crush-induced neuropathies.
Acetylcarnitine↗
Acute stress induces time-dependent responses in dopamine mesolimbic system.
Exposure to either restraint or footshock (3-60 min) induced similar biphasic alterations of 3-methoxytyramine (3-MT) concentrations (initial increase followed by decrease below control levels) in the nucleus accumbens septi (NAS) of mice, as revealed by tissue analysis. The only difference between the two stressors was the earlier onset of the decrease phase in the restrained mice. In both stressful conditions acid metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) increased throughout stress, while no significant changes in dopamine (DA) concentrations occurred. These data suggest biphasic alteration of DA release during prolonged stress exposure. The analysis of release in restrained conscious rats by in vivo microdialysis (10-240 min) showed a similar biphasic DA evolution (initial increase followed by decrease below baseline levels) in the NAS. The only difference from the previous experiment was the delayed onset of the decrease phase. Similar changes in DOPAC and HVA were also evident. Moreover, freed rats showed an immediate increase of DA release over baseline levels, also indicating that depletion of the neurotransmitter cannot account for the reduction of released DA. Taken together, these results support the hypothesis that biphasic alteration of DA transmission in the mesolimbic system is a general response to stress and suggest that the initial increase of DA release represents an arousal response while the subsequent decrease in DA release may be related to coping failure.
3,4-Dihydroxyphenylacetic Acid↗
Hippocampal type I and type II corticosteroid receptor affinities are reduced in rats predisposed to develop amphetamine self-administration.
It has been suggested that individual predisposition to develop amphetamine self-administration is associated with impairment in corticosteroid negative feedback mechanisms. Since corticosteroid receptors, particularly those in the hippocampus, are involved in corticosterone feedback sensitivity, we examined the relation between individual differences in amphetamine self-administration and characteristics of hippocampal corticosteroid receptors. Rats were selected on the basis of likelihood to self-administer amphetamine and designed as: (1) High Responding (HR) rats, who quickly acquire the response and (2) Low Responding (LR), who fail to self-administer amphetamine. We found lower affinities both for hippocampal type I and type II corticosteroid receptors in the HR animals. These data suggest that modification of hippocampal corticosteroid receptors may be responsible for the predisposition of some animals for amphetamine self-administration. Because HR rats also show a greater behavioral and endocrinological response in a novel environment, these differences in affinities suggest a relation among amphetamine self-administration, control of the corticosterone feedback loop, serum levels of corticosterone and characteristics of hippocampal corticosteroid receptors. The implication is that pharmacological manipulations of corticosteroid receptors may reveal new therapeutic strategies for drug abuse.
Adrenalectomy↗
Life events-induced decrease of corticosteroid type I receptors is associated with reduced corticosterone feedback and enhanced vulnerability to amphetamine self-administration.
In this study, we attempted to find out whether a social stress-induced increase in the vulnerability to acquire amphetamine self-administration was associated with a change in number of hippocampal corticosteroid receptors. This was examined in two types of sex-mixed colonies of rats. Animals were maintained for 4 weeks in: (1) 'stable social condition', membership did not change after constitution of the colony; (2) 'unstable social condition', the males were changed daily in a random design. The animals living in the 'stable social' conditions had: (1) a lower number of hippocampal type I corticosteroid receptors; (2) a longer duration of the increase in plasma corticosterone after exposure to novelty; (3) a higher vulnerability to acquire amphetamine self-administration. These findings suggest that a decrease in hippocampal type I corticosteroid receptors may be one of the biological mechanisms responsible for the impaired corticosterone feedback control observed in vulnerable animals. These findings throw more light on the role of hypothalamo-pituitary-adrenal axis in the modulation of adaptive behavior. The availability of drugs which are specific for corticosteroid receptors could represent a new approach to the therapy of certain behavioral disturbances.
Adrenalectomy↗
Acetyl-L-carnitine enhances the response of PC12 cells to nerve growth factor.
We have demonstrated that treatment of rat pheochromocytoma (PC12) cells with acetyl-L-carnitine (ALCAR) stimulates the synthesis of nerve growth factor receptors (NGFR). ALCAR has also been reported to prevent some age-related impairments of the central nervous system (CNS). In particular, ALCAR reduces the loss of NGFR in the hippocampus and basal forebrain of aged rodents. On these bases, a study on the effect of NGF on the PC12 cells was carried out to ascertain whether ALCAR induction of NGFR resulted in an enhancement of NGF action. Treatment of PC12 cells for 6 days with ALCAR (10 mM) stimulated [125I]NGF PC12 cell uptake, consistent with increased NGFR levels. Also, neurite outgrowth elicited in PC12 cells by NGF (100 ng/ml) was greatly augmented by ALCAR pretreatment. When PC12 cells were treated with 10 mM ALCAR and then exposed to NGF (1 ng/ml), an NGF concentration that is insufficient to elicit neurite outgrowth under these conditions, there was an ALCAR effect on neurite outgrowth. The concentration of NGF necessary for survival of serum-deprived PC12 cells was 100-fold lower for ALCAR-treated cells as compared to controls. The minimal effective dose of ALCAR here was between 0.1 and 0.5 mM. This is similar to the reported minimal concentration of ALCAR that stimulates the synthesis of NGFR in these cells. The data here presented indicate that one mechanism by which ALCAR rescues aged neurons may be by increasing their responsiveness to neuronotrophic factors in the CNS.
Acetylcarnitine↗
Changes in brain dopamine and acetylcholine release during and following stress are independent of the pituitary-adrenocortical axis.
Microdialysis was employed to assess extracellular dopamine from medial prefrontal cortex, nucleus accumbens, nucleus caudatus, and acetylcholine from the hippocampus of conscious rats during and after 120 min restraint stress. Restraint stress rapidly stimulated the release and the metabolism of dopamine in the medial prefrontal cortex and in the nucleus accumbens, and acetylcholine release in the hippocampus. Fifty-sixty min later, although rats were still restrained, dopamine and acetylcholine release gradually returned to basal levels. When the animals were freed a considerable increase in the release of both neurotransmitters was observed. No changes in the striatum were observed throughout the experiments. The time-course of plasma corticosterone did not parallel that of dopamine and acetylcholine release, increasing during the whole stress procedure, and decreasing when the animals were released. Adrenalectomized rats responded to stress and liberation in much the same way as intact rats. The administration of exogenous corticosterone (0.5-1.5 mg/kg s.c.) did not change the release of dopamine from the prefrontal cortex and nucleus accumbens, and of acetylcholine from the hippocampus, while the dose of 3.0 mg/kg which stimulated them, raised plasma corticosterone to very high concentrations which had never been attained during stress. Moreover, RU 38486, an antagonist of brain glucocorticoid receptors, did not antagonize the stress-induced increase of neurotransmitter release.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylcholine↗
Ordered disorder in the aged brain.
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Aging↗
In vivo probing of the brain cholinergic system in the aged rat. Effects of long-term treatment with acetyl-L-carnitine.
The regulation of acetylcholine (ACh) release by the different subtypes of muscarinic (M) receptors in the hippocampus of freely-moving Fischer and Sprague-Dawley rats, was investigated. Atropine (10 mumol/kg i.p.) induced a pronounced increase of ACh release (+400% over basal values) in the hippocampus of young rats (3 months) while the effect was drastically reduced (+100% over basal values) in old rats (24 months). The preferential M2 antagonist AF-DX 116 (50 mumol/kg i.p.) showed similar effects in young and old rats being, furthermore, 10 times less potent than atropine. The preferential M1 antagonist pirenzepine (50 mumol/kg i.p.) was even less potent than AF-DX 116 in enhancing ACh release in young rats, while the effect was more pronounced in the old ones. Therefore, the effect of the preferential M3 antagonist 4-DAMP was studied. 4-DAMP 10(-6) M, dissolved in the Ringer solution perfusing the hippocampus, induced an enhancement of ACh release (+200% and +70% over basal values, in young and old rats, respectively) which was comparable to that obtained after atropine at the same concentration. AF-DX 116 and pirenzepine, on the other hand, were by far less potent. Six months' pretreatment with acetyl-l-carnitine (ALCAR) reduced the significant differences between young and old rats in the release response after M1 and M3 receptor antagonists. Taken all together, these findings indicate that the regulation of ACh release, at least in the hippocampus, is mainly through the M3 receptors subtype of muscarinic receptors and that this subtype is the most involved in the aging process. Moreover, the ability of ALCAR to preserve the receptor-mediated functional ACh release response with respect to old animals suggests that ALCAR could be utilized in the amelioration of receptor functionality in the aging brain.
Acetylcarnitine↗
Pituitary-adrenocortical and pineal activities in the aged rat. Effects of long-term treatment with acetyl-L-carnitine.
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Acetylcarnitine↗
Evidence for a specific role of vasopressin in sustaining pituitary-adrenocortical stress response in the rat.
In the adult male Wistar rat a 2-fold 2-min restraint stress exposure, repeated 15 min apart, activated the adrenocortical secretion more than a single one would have. However, in rats with a pharmacological block of the endogenous CRF release, exogenous CRH (0.3 micrograms/kg iv), administered 15 min after a first similar dose, was unable to stimulate pituitary-adrenocortical activity above the level attained with the first peptide injection. On the contrary, in the same conditions exogenous arginine vasopressin (AVP) (0.3 micrograms/kg iv) administered 15 min after CRH, was able to further stimulate pituitary-adrenocortical activity. Using the same experimental procedure, oxytocin (0.3 micrograms/kg iv) was found to be totally inactive. The physiological import of these findings was investigated in the Brattleboro rat, genetically lacking in endogenous AVP, in which, unlike the control Long-Evans strain, the 2-fold stress exposure did not cause an increase in plasma corticosterone concentration greater than that of a single exposure. These results suggest that endogenous AVP is essential in sustaining adrenocortical activation in circumstances in which pituitary refractoriness towards CRH stimulation intervenes.
Anesthesia↗
Nerve growth factor modulates the activation of the hypothalamo-pituitary-adrenocortical axis during the stress response.
In the present study, we have investigated the functional relationship between the nerve growth factor protein (NGF) and the hypothalamus-pituitary-adrenocortical axis (HPAA). We have found that while iv injected NGF is able to stimulate the HPAA activity in rats, NGF is not able to stimulate the axis after a block of the hypothalamus produced by chlorpromazine-morphine-Nembutal treatment. Also, the stress activation of the HPAA is significantly reduced by pretreatment of the rats with anti-NGF immunoglobulin G. These results suggest that the stimulatory action of NGF on HPAA activity requires the release of ACTH secretagogues from the hypothalamus and that NGF may modulate the HPAA response to stress stimuli.
Animals↗
Hippocampal glucocorticoid receptor and behavior: a correlative study in rats and mice.
A correlation has been demonstrated between binding capacity for [3H]corticosterone in the hippocampus and the performance in passive and active avoidance in the rat, and impaired behavior in adrenalectomized rats by exogenous corticosterone is restored. On this basis we have studied the possible correlation between strain-dependent behavioral differences and the glucocorticoid binding capacity in the hippocampus in mice and rats. In Naples high- (NHE) and low-excitability (NLE) rat strains, genetically selected on the basis of divergent locomotor activity upon forced exposure to a spatial novelty situation, no differences were found in glucocorticoid maximal binding capacity while both strains had a lower capacity than Naples random-breed (NRB) control rats. However, the intra-strain correlative analysis of hippocampal glucocorticoid receptors number and behavioral scores demonstrated that motor and emotional indexes of arousal to novelty were positively correlated in NLE-and negatively in NHE- while no correlation was present in NRB rats. Using two inbred strains of mice, C57BL/6 and Balb/c, extensively investigated for learning abilities, the lower active avoidance score of C57BL/6 was associated with a lower binding capacity for [3H]corticosterone in the hippocampus. Altogether the above results support the involvement of the hippocampal glucocorticoid receptor in the modulation of some adaptive behavioral responses, while do not prove that genetic differences in behavior rest on parallel differences in binding capacity for glucocorticoid hormone.
Aging↗
Influence of 6-OHDA lesion of central noradrenergic systems on corticosteroid receptors and neuroendocrine responses to stress.
Two types of receptor for adrenocortical hormones (type I or mineralocorticoid and type II or glucocorticoid) in the hippocampus and hypothalamus mediate the effects of corticosteroids on various brain functions including the negative feedback control of hypothalamo-pituitary-adrenal (HPA) axis activity. These brain regions are also densely innervated by noradrenergic terminals which may play a role in the regulation of HPA axis activity and the feedback action of corticosteroids. However, direct evidence for a noradrenergic control of corticosterone receptors is lacking. The present experiments tested the effects of 6-hydroxydopamine lesion of noradrenergic ascending pathways at the level of the pedunculus cerebellaris superior (PCS) on the status of type I and type II corticosteroid receptors. Binding of [3H]corticosterone was evaluated in cytosolic fractions of 24-h adrenalectomized animals 3 weeks after surgery. The PCS lesion produced an up-regulation of type I corticosteroid receptors in the hippocampus and of the type II receptor in the hypothalamus. The number of these receptors (Bmax) increased without any change in their affinity for corticosterone (Kd). Furthermore, in a functional study, we tested the effects of the lesion on the neuroendocrine responses to stress. Plasma corticosterone levels were lower in lesioned rats both under basal conditions and in response to the stress of gentle handling or exposure to footshock, indicating reduced activity of the HPA axis. These results are in line with recent studies indicating a facilitatory function of noradrenergic pathways on the HPA axis and suggest that this action could be mediated via a modulation of corticosteroid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
NMDA receptors and in vivo dopamine release in the nucleus accumbens and caudatus.
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Animals↗
Aging brain: effect of acetyl-L-carnitine treatment on rat brain energy and phospholipid metabolism. A study by 31P and 1H NMR spectroscopy.
The effects of acetyl-L-carnitine (ALCAR) on metabolites involved in energy and phospholipid metabolism have been evaluated by mean of 31P and 1H NMR spectroscopy on adult (6 months) and old (24 months) rat brains. A significant increase of glycerophosphorylcholin (GroPCho) in aged rat brain has been observed as compared with adult rat brain. No variations in ATP, phosphocreatine (PCr), Cr, lactate, ADP and inorganic phosphate (Pi) levels have been found between aged and adult brains. Treatment with ALCAR caused a significant increase in PCr levels and a decrease in lactate and sugar phosphate in adult and aged rat brain. These results are suggestive of treatment with ALCAR being responsible for a reduction in brain glycolytic flow and for enhancing the utilization of alternative energy sources, such as lipid substrates or ketone bodies. Furthermore, the changes in GroPCho levels observed after treatment with ALCAR may be indicative of a modulating effect on the activity of the enzymes involved in the acylation-re-acylation process of membrane phospholipids.
Acetylcarnitine↗