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

Brunello, Nicoletta; Riva, Marco A.; Rovescalli, A; Galimberti, R.; Racagni, Giorgio

doi:10.1111/j.1600-0773.1988.tb00930.x

Cited by 39 publications

(9 citation statements)

References 42 publications

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“…It is interesting to note that similar results have been obtained in the cerebral cortex of aged animals (Brunello et al, 1988) and in the frontal cortex of aged volunteers (Severson et al, 1985). This further supports the hypothesis that circulating lymphocytes and platelets are a convenient tissue and a readily accessible model to study human neurotransmitter receptor systems since changes in these peripheral cells may reflect alterations in receptor responsiveness in a less accessible target tissue as the brain.…”

Section: Discussionsupporting

confidence: 73%

Changes of lymphocyte beta‐adrenergic receptors and platelet serotonin reuptake sites in aging and dementias

Rozza¹,

Scavini²,

Steardo³

et al. 1993

Human Psychopharmacology

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We have studied the kinetic constants of 8-adrenergic receptors in lymphocytes and of serotonin uptake sites in platelets from adult and elderly volunteers and from aged patients with a diagnosis of multi-infarct dementia (MID) or senile dementia of Alzheimer's type (SDAT). The results showed that in the physiological aging process, 8-adrenergic receptor density is reduced and SHT transport system is enhanced. MID is associated to a loss of 8-adrenoceptor affinity and a slight increase in the capacity of 5HT uptake. The kinetic constants of bothb-adrenergic receptors in lymphocytes and 5HT uptake sites in platelets from SDAT patients were comparable to those observed in the adult population, being thus different from those found in the aged matched volunteers.These changes could be interpreted as resulting from compensatory mechanisms that replaced altered plasma monoamhe concentrations. The apparent absence of such changes in SDAT patients could suggest the lack of these compensatory effects.KEY worn-Dementia, lymphocyte, platelet, beta-adrenergic receptor, serotonin reuptake site.

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Section: Discussionsupporting

confidence: 73%

Changes of lymphocyte beta‐adrenergic receptors and platelet serotonin reuptake sites in aging and dementias

Rozza¹,

Scavini²,

Steardo³

et al. 1993

Human Psychopharmacology

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“…Enhanced 5-HT turnover (Moretti et al, 1987) and a reduction in 5-HT affinity (Brunello et al, 1988) have been reported. Relevant to the HPA axis, 5-HT receptors in the hypothalamus undergo changes in affinity with advanced age (Halpern et al, 1989).…”

Section: Introductionmentioning

confidence: 97%

Age-dependent loss of corticosterone modulation of central serotonin 5-HT1A receptor binding sites

Dugar

et al. 1998

J. Neurosci. Res.

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A loss of endocrine and neurotransmitter system interactions, including corticosterone regulation of 5-HT1A receptors, may underlie the age-related deficits in the hypothalamic-pituitary-adrenal (HPA) axis including adapting to stress. In this study, female Fischer 344 rats, (ages 3, 13, and 18 months), were bilaterally adrenalectomized and supplemented for 3 weeks with placebo or corticosterone (200 mg or 600 mg) containing 21 day sustained-release pellets implanted subcutaneously (LC, MC, or HC, respectively). Scatchard analysis using the 5-HT1A receptor agonist [3H]8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT) demonstrated a significant decrease in hippocampal receptor density in 3 month and 13 month MC groups (-35.2 and -32.1%, respectively) as compared to age-matched LC groups; a significant decline in 5-HT1A receptor density in 3 month and 13 month HC groups was found compared to age-matched MC groups (-16.7 and -22.0%, respectively). However, these hormone treatments (LC or HC) failed to alter hippocampal 5-HT1A binding site density in the 18 month groups. Cortical 5-HT1A receptor densities were altered in a similar age-dependent manner. In contrast, the density of hypothalamic 5-HT1A receptors in the 18 month LC group was significantly increased above that in the 3 month LC group. An additional indicator of the hippocampal response to corticosterone, the distribution of glial fibrillary acidic protein (GFAP), revealed an age-related decline in responsiveness to hormone treatment in the oldest group. The present study has identified an age-associated deficit in the regulation of hippocampal 5-HT1A receptors by corticosterone which may underly the diminished capacity of the aging HPA axis to cope with stress.

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“…Radioligand-binding studies in rat brain have demonstrated that there is a decrease in the number of serotonin receptors, including 5-HT 2 receptors, as the animals age (Allen et al 1983;Brunello et al 1988). There is also increased turnover of serotonin and a reduction in serotonin high-a¦nity uptake (Brunello et al 1988).…”

Section: Discussionmentioning

confidence: 98%

“…There is also increased turnover of serotonin and a reduction in serotonin high-a¦nity uptake (Brunello et al 1988). Thus, there is evidence to suggest that the senescence-related dysfunction of the serotonergic system may contribute to the age-related increase seen in the amount of rat neocortical HVSs.…”

Section: Discussionmentioning

confidence: 98%

“…Recent in vitro (Pape and McCormick 1989;McCormick and Wang 1991;McCormick 1992) and in vivo (Jäkälä et al 1995 electrophysiological evidence has suggested that activation of serotonin (5-hydroxytryptamine; 5-HT) subtype 2 receptors can suppress thalamocortical oscillations. Therefore, since the amount of HVSs increases with age (Buzsáki et al 1988(Buzsáki et al , 1990aSirviö et al 1989;Riekkinen Jr et al 1991a), and age-related deÞciences in both cholinergic (Wu et al 1988;Riekkinen Jr et al 1992) and serotonergic (Allen et al 1983;Brunello et al 1988) markers are observed in rat brain, impaired functioning of both of these ascending systems could contribute to the age-related electrophysiological abnormalities in the thalamocortical systems (see e.g. Sirviö et al 1994).…”

Section: Introductionmentioning

confidence: 98%

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Activation of acetylcholine receptors and 5-HT 2 receptors have additive effects in the suppression of neocortical high-voltage spindles in aged rats

et al. 1997

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We investigated if activation of the muscarinic or nicotinic acetylcholine receptors and serotonin (5-hydroxytryptamine; 5-HT) subtype 2 receptors would have additive or synergistic effects on the suppression of thalamocortically generated rhythmic neocortical high-voltage spindles (HVSs) in aged rats. The 5-HT2 receptor antagonist, ketanserin, at a moderate dose (5 mg/kg) prevented the ability of a muscarinic acetylcholine receptor agonist, (oxotremorine 0.1 mg/kg), and a nicotinic acetylcholine receptor agonist (nicotine 0.1 mg/kg), to decrease HVSs. At a higher dose (20 mg/kg), ketanserin completely blocked the decrease in HVSs produced by moderate doses of muscarinic acetylcholine receptor agonists (pilocarpine 1 mg/kg and oxotremorine 0.1 mg/kg), and by a high dose of nicotine (0.3 mg/kg), though not that produced by high doses of pilocarpine (3 mg/kg) and oxotremorine (0.9 mg/kg). The ability of a 5-HT2 receptor agonist, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.1-1.0 mg/kg), to suppress HVSs was non-significantly modulated by the nicotinic acetylcholine receptor antagonist, mecamylamine (1-15 mg/kg), and the muscarinic acetylcholine receptor antagonist, scopolamine (0.03-0.3 mg/kg). The effects of the drugs on behavioral activity could be separated from their effects on HVSs. The results suggest that activation of the muscarinic or nicotinic acetylcholine receptors plus 5-HT2 receptors has additive effects in the suppression of thalamocortical oscillations in aged rats.

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

Cited by 39 publications

References 42 publications

Changes of lymphocyte beta‐adrenergic receptors and platelet serotonin reuptake sites in aging and dementias

Changes of lymphocyte beta‐adrenergic receptors and platelet serotonin reuptake sites in aging and dementias

Age-dependent loss of corticosterone modulation of central serotonin 5-HT1A receptor binding sites

Activation of acetylcholine receptors and 5-HT 2 receptors have additive effects in the suppression of neocortical high-voltage spindles in aged rats

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