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Biomedical subjects

M L Porceddu

Publications and source records attributed to M L Porceddu.

At least 19 recordsLinked to original sources
PubMed1990

Differential effect of aging on 3H-SCH 23390 binding sites in the retina and in distinct areas of the rat brain.

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.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

D1 dopamine receptors in the rat retina: effect of dark adaptation and chronic blockade by SCH 23390.

Chronic administration of SCH 23390 (0.03 mg/kg s.c., three times daily), a selective D1 dopamine (DA) receptor blocker, markedly increased the [3H]SCH 23390 binding in the rat retina. As revealed by the Scatchard plot analysis of saturation data from retinal homogenates, chronic SCH 23390 increased the total number of binding sites by 34% when compared to tissue from solvent-treated rats but failed to change the apparent affinity of [3H]SCH 23390 for its binding sites. The up-regulation of [3H]SCH 23390 binding sites was paralleled by an increase in the sensitivity of retina DA-sensitive adenylate cyclase. In fact, DA (5 X 10(-6) M to 10(-4) M) produced a higher accumulation of cyclic AMP (from 58 to 128%) in the retina of SCH 23390-treated rats as compared to the accumulation (from 35 to 80%) found in tissue from solvent-treated rats. Since dark adaptation decreases dopaminergic function in the rat retina, the influence of environmental lighting on [3H]SCH 23390 binding and DA-sensitive adenylate cyclase activity was studied. After 4 h of dark adaptation the density of [3H]SCH 23390 binding sites was higher (32%) than that from light-adapted rats. On the other hand, dark adaptation failed to change the apparent affinity of [3H]SCH 23390 for its binding sites. Moreover, DA elicited a greater stimulation of adenylate cyclase activity in homogenates of retina from dark-adapted rats. Thus, the maximum adenylate cyclase response to DA resulted higher in the retina of dark-adapted rats (152%) than that found in the retina of light-adapted animals (97%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1987

6-Hydroxydopamine-induced degeneration of nigral dopamine neurons: differential effect on nigral and striatal D-1 dopamine receptors.

Dopamine-sensitive adenylate cyclase and 3H-SCH 23390 binding parameters were measured in the rat substantia nigra and striatum 15 days after the injection of 6-hydroxydopamine into the medial forebrain bundle. The activity of nigral dopamine-sensitive adenylate cyclase and the binding of 3H-SCH 23390 to rat nigral D-1 dopamine receptors were markedly decreased after the lesion. On the contrary, 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine pathway enhanced both adenylate cyclase activity and the density of 3H-SCH 23390 binding sites in striatal membrane preparations. The changes in 3H-SCH 23390 binding found in both nigral and striatal membrane preparations were associated with changes in the total number of binding sites with no modifications in their apparent affinity. The results indicate that: within the substantia nigra a fraction (30%) of D-1 dopamine receptors coupled to the adenylate cyclase is located on cell bodies and/or dendrites of dopaminergic neurons; striatal D-1 dopamine receptors are tonically innervated by nigrostriatal afferent fibers.

Adenylyl Cyclases↗
PubMed1987

Developmental and age-related changes in D1-dopamine receptors and dopamine content in the rat striatum.

The relationship between the postnatal development of dopaminergic (DAergic) nerve endings and the maturation of D1 DA receptors in the rat striatum was analyzed by measuring the content of DA and dihydroxyphenylacetic acid (DOPAC), two biochemical markers of DAergic nerve terminal proliferation, and the ontogenetic changes in [3H]SCH 23390 binding sites. DA-stimulated adenylate cyclase (AC) activity was also measured in order to characterize the coupling of [3H]SCH 23390 binding sites to the responses mediated by the activation of D1 DA receptors. Striatal levels of DA and DOPAC, as well as the density and affinity of [3H]SCH 23390 binding sites and DA-stimulated AC activity were also measured in senescent rats. The striatal content of DA increased slowly after birth, reaching adult levels by postnatal day 60 and remaining constant through adulthood and senescence (up to 20 months of age). The density of [3H]SCH 23390 binding sites increased 14-fold from birth to postnatal day 35, when a peak value was reached, whereas a significant decrease was observed in the striatum of aged rats. In contrast, the affinity of D1 DA receptors for [3H]SCH 23390 remained unchanged from birth through senescence. The stimulation of cyclic AMP formation induced by 100 microM DA increased 4-fold from birth to postnatal day 14, when the maximal responsiveness to DA was observed and then returned to adult levels. No significant alterations were observed in the Km values during development, whereas the stimulatory effect of 100 microM DA on AC activity was significantly decreased in senescent rats.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

3H-SCH 23390 binding sites in the rat substantia nigra: evidence for a presynaptic localization and innervation by dopamine.

Chronic treatment with SCH 23390, a selective D-1 dopamine receptor antagonist, elicited a 32% increase in the density of 3H-SCH 23390 binding sites in nigral membrane preparations but failed to change the apparent KD of the ligand for its binding sites. Haloperidol, a D-2 dopamine receptor antagonist which blocks the dopamine-sensitive adenylate cyclase and (-) sulpiride, a selective D-2 dopamine receptor blocker, which does not block the dopamine-sensitive adenylate cyclase, failed to change both the Bmax and KD of 3H-SCH 23390 binding. Finally, the intrastriatal injection of kainic acid produced a marked decrease of both GAD activity and GABA content and 3H-SCH 23390 binding sites (65%) in the homolateral substantia nigra. The results show that in the rat substantia nigra most of the 3H-SCH 23390 binding sites have a presynaptic localization on the striato-nigral GABAergic afferent terminals and suggest that dopamine released from nigral dendrites exerts a tonic influence on these presynaptic D-1 dopamine receptors.

Animals↗
PubMed1986

Striato-nigral denervation increases type II benzodiazepine receptors in the substantia nigra of the rat.

The degeneration of the striato-nigral projection induced by the injection of kainic acid into the striatum produced a 30% increase in the density of type II benzodiazepine binding sites (measured as the proportion of [3H]flunitrazepam which remained after the addition of 2 X 10(-7) M CL 218872). The lesion did not change the number of type I benzodiazepine binding sites (measured using [3H]ethyl-beta-carboline-3-carboxylate). The increase of type II benzodiazepine binding sites persisted and was markedly enhanced in the substantia nigra, previously lesioned with kainic acid. In fact, the injection of kainic acid into the nigra caused, 3 weeks after the treatment, a 80% decrease in the total number of type I benzodiazepine binding sites, and no change in the number of type II benzodiazepine binding sites. The density of type II sites increased by 70% following a subsequent injection of kainic acid into the striatum, homolateral to the lesioned substantia nigra. The results suggest that type I benzodiazepine binding sites in the nigra are located on kainic acid-sensitive elements (probably intrinsic neurones), while type II benzodiazepine binding sites, the number of which increased after degeneration of the striato-nigral pathway, are localized on kainic acid-resistant structures (probably axons or terminals) that receive an input from striatal afferents and from interneurones in the nigra.

Animals↗
PubMed1985

[3H]SCH 23390 binding sites increase after chronic blockade of D-1 dopamine receptors.

Chronic treatment with SCH 23390, a selective D-1 dopamine receptor antagonist, increased (40%) the density of [3H]SCH 23390 binding sites in striatal membrane preparations but failed to change the apparent KD of the ligand for its binding sites. Haloperidol, which preferentially blocks D-2 receptors, induced only a slight, not significant increase in the total number of [3H]SCH 23390 binding sites. (-)Sulpiride, a selective D-2 receptor blocker, also failed to change either Bmax or KD of [3H]SCH 23390 binding. Thus, chronic blockade of D-1 receptor sites by SCH 23390 can lead to an increase in their total number.

Adenylyl Cyclases↗
PubMed1985

Increase in nigral type II benzodiazepine recognition sites following striatonigral denervation.

In the rat substantia nigra Type II benzodiazepine recognition sites (measured as the portion of [3H]flunitrazepam binding which remain after the addition of 2 X 10(-7) M Cl 218872) represent 50% of the total benzodiazepine recognition sites. The density of Type II sites was increased by 35% following the degeneration of the striatonigral afferents induced by the intrastriatal injection of kainic acid. On the other hand the same lesion failed to change the density of the remaining nigral Type I sites. The results indicate that denervation induces supersensitivity to nigral Type II benzodiazepine recognition sites.

Animals↗
PubMed1985

Sedation and sleep induced by high doses of apomorphine after blockade of D-1 receptors by SCH 23390.

The effect of SCH 23390, a selective blocker of D-1 receptors, on apomorphine-induced behavioural and EEG changes was studied in rats. In control rats, a low dose of apomorphine (50 micrograms/kg s.c.) produced sedation associated with EEG synchronization. A high dose of apomorphine (1 mg/kg s.c.) produced stereotypy associated with EEG desynchronization. At the dose of 1 mg/kg i.p., SCH 23390 decreased motor activity but failed to alter the EEG pattern. The administration of either the low or high dose of apomorphine to SCH 23390-treated rats elicited a marked sedative response associated with EEG synchronization. The EEG synchronization produced by apomorphine (50 micrograms/kg) in SCH 23390-treated rats was prevented by (-)-sulpiride (25 mg/kg i.p.), a D-2 receptor blocker. It is concluded that by preventing the excitatory response to apomorphine SCH 23390 discloses the existence of a population of D-2 receptors mediating sedation and sleep.

Animals↗
PubMed1979

Evidence for a GABAergic projection from the substantia nigra to the ventromedial thalamus and to the superior colliculus of the rat.

Unilateral intranigral infusion of kainic acid (1.5 microgram) produced neuronal loss in the lateral two-thirds of the nigra while sparing axons en passage. Fink-Heimer silver impregnation revealed dense terminal degeneration in the nigra itself (both in the compacta and in the reticulata) and in areas of non-dopaminergic nigral projection such as the ventromedial (VM) nucleus of the thalamus, the superior colliculus and the reticular formation; only spare terminal degeneration was found in areas of dopaminergic projection such as the caudate and septum. In order to clarify the nature of the transmitter of the nigrothalamic and nigrocollicular neurons, the activity of glutamic decarboxylase (GAD), the marker of cholinergic neurons, was measured in the VM and ventrobasal (VB) thalamus and in the nigra of each side, 7 days after unilateral intranigral injection of kainic acid. GAD activity was reduced significantly in the VM-thalamus (-33%), in the superior colliculus (-40%) and in the substantia nigra (-18%) but not in the VB-thalamus of the lesioned side. CAT remained unchanged in these areas. Similar results were obtained in the thalamus and in the superior colliculus after electrocoagulative lesions of the nigra. The results indicate the existence of a nigrothalamic and of a nigrocollicular GABAergic pathway. This projection might play an important role in motor coordination and gaze control.

Animals↗
PubMed1979

Substantia nigra as an out-put station for striatal dopaminergic responses: role of a GABA-mediated inhibition of pars reticulata neurons.

Intranigral administration of kainic acid results in loss of pars reticulata neurons without damage to axons traversing or terminating within the nigra. Unilateral nigral lesions with kainic acid result in an ipsilateral turning upon administration of apomorphine, a dopamine (DA)-receptor agonist and in contralateral turning upon administration of haloperidol, a DA-receptor blocker. Destruction of post-synaptic structures in the striatum of the side contralateral to that injected with kainic acid results in a drastic reduction, abolition or even reversal of the turning effects elicited by apomorphine and haloperidol. Unilateral intranigral microinjection of nanogram amounts of the GABA-receptor antagonists picrotoxin and bicuculline elicits ipsilateral circling upon apomorphine administration. Kainic-induced lesion or microinjection of picrotoxin or bicuculline in the nigra ipsilateral to a 6-OHDA-lesion of nigro-striatal DA-neurons results in reduction, abolition or reversal of the contralateral circling produced by apomorphine. The results indicate that the nigra pars reticulata is a station for dopaminergic impulses originating from the striatum and suggest that the turning behavior in response to striatal DA-receptor stimulation is due to a GABA-mediated inhibition of ipsiversive pars reticulata neurons.

Animals↗
PubMed1979

Opposite turning effects of dainic and ibotenic acid injected in the rat substantia nigra.

Unilateral intranigral administration of kainic and ibotenic acid, two putative stimulants of glutamatergic mechanisms, elicited turning behaviour starting from doses of 10 ng. While the turning produced by kainic acid was ipsilateral, that produced by ibotenic acid was contralateral to the injected side. Previous destruction of dopaminergic neurons on the side of the intranigral injection failed to reduce the turning behaviour. Peripheral treatment with picrotoxin did not reduce the turning in response to ibotenic acid. The results might suggest the existence of excitatory and inhibitory glutamate receptors which control nigral non-dopaminergic neurons mediating turning-behaviour.

Animals↗
PubMed1978

Stimulation of "regulatory" dopamine receptors by bromocriptine (CB-154).

Bromocriptine produces long-lasting hypomotility and decreases brain dihydroxyphenylacetic acid (DOPAC) in mice. These effects are obtained with doses much lower than those which produce hypermotility. The decrease of brain DOPAC is correlated to the hypomotility both on a dose and on a time basis. Potent DA receptor blockers as pimozide, benzperidol and droperidol antagonize the hypomotility and the decrease of brain DOPAC produced by bromocriptine. These effects are obtained with very low doses (0.05-0.3 mg/kg) of neuroleptics which per se do not affect motility or brain DOPAC. The maximal decrease of brain DOPAC produced by bromocriptine is similar to that produced by apomorphine and the combination of these drugs does not result in a further decrease. On the basis of these results it is postulated that bromocriptine decreases DA turnover and produces hypomotility by acting on "regulatory" DA receptors different from the postsynaptic ones of the "terminal" dopaminergic areas.

3,4-Dihydroxyphenylacetic Acid↗