Dopamine receptor sensitivity in brain and retina of rats during aging

Govoni, Stefano; Loddo, P.; Spano, PierFranco; Trabucchi, M.

doi:10.1016/0006-8993(77)90695-3

Cited by 112 publications

(15 citation statements)

References 13 publications

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“…In addition, the density of 3H-SCH 23390 binding sites is significantly higher in the retina of aged rats than in 3-month-old controls. Our finding that the density of 3H-SCH 23390 binding sites is reduced in the substantia nigra and tuberculum olfactorium of senescent rats is in agreement with a previous report on the age-related decrease in the responsiveness to DA of adenylate cyclase activity in these two brain areas (Govoni et al, 1977).…”

Section: Discussionsupporting

confidence: 93%

“…Different laboratories have also reported age-related decreases in the responsiveness to DA of adenylate cyclase activity in several areas of the rat brain (Govoni et al, 1977;Schmidt and Thornberry, 1978;Giorgi et al, 1987b). Therefore, a concomitant reduction in the density of D-1 DA receptors can be expected to occur in the brain of senescent rats.…”

Section: Introductionmentioning

confidence: 95%

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Differential effect of aging on3H-SCH 23390 binding sites in the retina and in distinct areas of the rat brain

Giorgi

Porceddu

Pepitoni

et al. 1990

J. Neural Transmission

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The effects of age on the binding parameters of the selective D-1 dopamine (DA) receptor antagonist 3H-SCH 23390 were studied in membrane preparations from rat striatum, substantia nigra, olfactory tubercle, prefrontal cortex and retina. When compared with 3-month-old animals, there was a significant decrease in the density of 3H-SCH 23390 binding sites in the striatum (-25%), substantia nigra (-24%), and olfactory tubercle (-23%), but not in the prefrontal cortex of senescent (23-month-old) rats. The affinity of 3H-SCH 23390 for D-1 DA receptors did not change with age in any of the brain areas analyzed. In contrast, the density of 3H-SCH 23390 binding sites was higher (+53%) in the retina of aged rats that in 3-month-old controls. Confirming previous studies, we observed that light deprivation induced a significant increment in the density of 3H-SCH 23390 binding sites in the retina of adult rats (+31%) but not in the retina of aged animals. The ability of light exposure to activate DAergic neurons in the rat retina was not altered by normal aging. In fact, a similar increase in the concentration of DOPAC was observed in the retina of light-adapted adult and senescent rats when compared to their respective dark-adapted controls (+94% and +95%, respectively). The results indicate that aging has a differential effect on D-1 DA receptors in the retina and different areas of the rat brain. Finally, the age-related increment in the density of retinal D-1 DA receptors does not appear to depend on presynaptic mechanisms, since DA metabolism is increased by light to the same extent in young and aged rats.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 95%

Differential effect of aging on3H-SCH 23390 binding sites in the retina and in distinct areas of the rat brain

Giorgi

Porceddu

Pepitoni

et al. 1990

J. Neural Transmission

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“…Along this line, particular attention has been given to dopaminergic transmission. An agerelated decline of this system is one of the most consistent findings in different labora tories [Finch, 1973;Govoni et al, 1977Govoni et al, , 1980Henry and Roth, 1986;Jonec and Finch, 1975]. The impairment of dopamin ergic transmission is of particular interest since the deficits measured in rodents and the correlated physiological and motor be havior patterns are similar to those observed in humans and make the animal model rele vant to the age-related changes in man.…”

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confidence: 84%

The Central Dopaminergic System: Susceptibility to Risk Factors for Accelerated Aging

et al. 1988

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The synaptic deficit of brain dopaminergic activity involves a complex pattern of changes both at presynaptic and at postsynaptic level. The aged dopaminergic nuclei present a reduced number of dopamine terminals, a decreased ability to synthesize and reuptake dopamine and defective recognition sites both in terms of absolute number of D₂ receptors and of transducing mechanisms linked to D₁ receptors. These changes suggest that the dopaminergic system may be particularly sensitive during aging to environmental, iatrogenic and toxic factors, which may easily make the elderly develop symptoms of central dopamine deficiency.

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“…Recently, we demonstrated an age-related decrease in the sensitivity to dopamine stimula tion of adenylate cyclase in striatum, substantia nigra (22) and dopaminergic areas of the limbic system of senescent rats (10). The involvement of the dopaminergic system in the events characterizing old age is a further indication of the pharmacological relevance of tire bio chemical changes induced by ergot alkaloids in this system.…”

mentioning

confidence: 93%

Ergot Alkaloids and Cyclic Nucleotides in the CNS

et al. 1978

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Ergotamine and dihydroergotamine show a higher blocking effect towards the dopamine-induced stimulation of adenylate cyclase activity than to the apomorphine-induced stimulation. This could reflect a possible specificity of the compound to dopaminergic receptor. Bromocriptine blocks in a more competitive way the activation of adenylate cyclase induced in vitro by dopamine, but increases the levels of cAMP in rat striatum in vivo. This effect is blocked by haloperidol and reserpine when given together with bromocriptine. On the base of the biochemical observation and various behavioral data the drug has been used in the treatment of parkinsonism with contrasting results and of Huntington’s chorea. Moreover, bromocriptine induces a marked decrease of cGMP levels in cerebellum such as haloperidol and chloropromazine while apomorphine and other dopaminergic drugs increase the levels of cGMP. At the dose of 1 mg/kg, bromocriptine as well as DH-ergotoxine markedly reduces the levels of striatal DOPAC.

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Dopamine receptor sensitivity in brain and retina of rats during aging

Cited by 112 publications

References 13 publications

Differential effect of aging on3H-SCH 23390 binding sites in the retina and in distinct areas of the rat brain

Differential effect of aging on3H-SCH 23390 binding sites in the retina and in distinct areas of the rat brain

The Central Dopaminergic System: Susceptibility to Risk Factors for Accelerated Aging

Ergot Alkaloids and Cyclic Nucleotides in the CNS

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