Biomedical subjects

T Di Paolo

Publications and source records attributed to T Di Paolo.

At least 19 recordsLinked to original sources

PubMed1992

Chronic estradiol treatment increases anterior pituitary but not striatal D2 dopamine receptor mRNA levels in rats.

The effect of chronic 17 beta-estradiol treatment (10 micrograms, twice each day, for 2 weeks) of ovariectomized rats on D2 dopamine (DA) receptor mRNA levels was investigated in striatum and anterior pituitary gland tissues. We used 32P-labeled probes specific for D2 receptor and beta-actin mRNAs in Northern blot analysis. The ratio of D2 DA receptor mRNA/beta-actin mRNA level was significantly increased in the anterior pituitary of estradiol-treated rats compared to vehicle-treated animals. The D2 DA receptor mRNA/beta-actin mRNA ratio in the striatum was not affected by estradiol treatment. However, the medial portion of the striatum showed a significantly lower ratio compared to the lateral portion of the striatum in both vehicle- and estradiol-treated rats. Thus, the estradiol effect on anterior pituitary D2 receptors may implicate transcriptional regulation, whereas our results do not support this hypothesis for the estradiol action on striatal D2 receptors.

Actins↗

PubMed1992

Changes of rat striatal neuronal membrane morphology and steroid content during the estrous cycle.

It is well documented that sex steroids affect striatal dopamine systems. However, the mechanism(s) of these hormonal effects in the striatum is still not well understood. We now report that gonadal steroid hormones during the estrous cycle affect the morphology and steroid hormone content of the rat striatum. Rats displaying at least two consecutive estrous cycles were included in this study as well as a group of female rats ovariectomized two weeks before being killed. The striatum was dissected from one half of each brain and used for morphological studies. From the other half of each brain, the striatum was dissected and steroid hormone concentrations in striatum and the remainder of the brain were determined. Tissues and serum concentrations of 17 beta-estradiol, progesterone and prolactin were measured by specific radioimmunoassays. Serum 17 beta-estradiol and prolactin concentrations peaked in proestrus, while progesterone was high in diestrus and proestrus. 17 beta-Estradiol levels were higher in the striatum than in the rest of the brain; both were also shown to fluctuate during the estrous cycle and with a pattern similar to that observed in serum. Progesterone serum levels showed a similar pattern of changes during the estrous cycle to progesterone concentrations in the striatum and the rest of the brain. The ultrastructure of the striatal dendritic membranes was studied by freeze-fracture. A significant difference in the content of intramembranous particles in dendritic shafts, which are mainly contacted by dopaminergic synapses, was found during the estrous cycle. The numerical density of large (greater than 10 nm) intramembranous particles was increased in diestrus I and II and in the afternoon of proestrus compared to estrus, the morning of proestrus and ovariectomized rats. In contrast, the numerical density of small (less than 10 nm) intramembranous particles was decreased in cycling animals compared to ovariectomized rats and fell in the afternoon of proestrus and then progressively increased in the following days to peak in the morning of proestrus. A negative correlation between steroid concentrations and small intramembranous particle density was observed, while the correlation was positive for large particles. No changes were observed in the membranes of dendritic spines, the main postsynaptic target for cortical afferents. In summary, this is the first report that concentrations of 17 beta-estradiol and progesterone in the striatum fluctuate during the estrous cycle. This is associated with estrous cycle-dependent changes of intramembranous particle density of striatal dendritic membranes. Our data therefore indicate that the striatum is a brain region hormonally modulated under physiological conditions.

Animals↗

PubMed1992

Effects of adrenalectomy and glucocorticoids on rat brain dopamine receptors.

The effects of adrenalectomy (ADX) and dexamethasone (DEX) treatment on brain dopamine (DA) receptors of ovariectomized (OVX) rats were investigated by autoradiography using binding of the D1 and D2 antagonists ligands [3H]SCH 23390 and [3H]spiperone, respectively. Fourteen days after ADX, D1 receptors decreased in the middle striatum (M.CPu) and in the dorsal area of the posterior striatum (P.CPu). A more pronounced decrease was observed in the substantia nigra (SN) and no significant changes occurred in the anterior striatum (A.CPu), globus pallidus (GP) and accumbens (Acb). D2 receptors decreased in the M.CPu and dorsal area of the P.CPu and remained unchanged in the A.CPu as compared to OVX rats. Twenty-eight days after ADX, D1 and D2 receptors decreased in the A.CPu (D2), in the M.CPu (D2) and substantially in the SN (D1). DEX treatment (14 days, 0.5 mg/kg, b.i.d., IM, starting 14 days after ADX) reversed these effects in the A.CPu (D2), M.CPu (D2) and SN (D1) when compared to ADX+OVX rats. DEX also increased the density of D1 receptors in Acb, A.CPu and M.CPu when compared to OVX rats. Striatal homogenates of rats treated chronically with ACTH and corticosterone had an increased density of D1 receptors while these treatments alone left these receptors unchanged, thus suggesting either a minor role or no role of the changes in ACTH levels following glucocorticoids manipulations. Our results suggest that the adrenals play a role in the modulation of DA receptors activity in the rat brain.

Adrenalectomy↗

PubMed1992

Effect of chronic estradiol treatment on brain dopamine receptor reappearance after irreversible blockade: an autoradiographic study.

Quantitative autoradiography was used to investigate dopamine receptor repopulation kinetics after irreversible dopamine receptor inactivation with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). The striatum and substantia nigra of two groups of ovariectomized female rats were compared. One group of rats was pretreated with estradiol (10 micrograms, twice daily, for 2 weeks), and another group received the vehicle. Striatal D1 dopamine receptors had larger degradation and production rate constants, compared with D2 receptors. The D2 receptor degradation rate constant increased rostro-caudally in the striatum of vehicle-treated rats, whereas this was not observed for estradiol-treated animals. A trend similar to that for D2 receptors was observed for the D1 receptor degradation rate constant in the striatum of vehicle-treated rats, whereas in estradiol-treated animals this constant decreased rostro-caudally. In the anterior and the middle parts of the striatum D2 receptor recovery parameters were not affected by chronic estradiol treatment, but in the posterior part estradiol-treated rats had lower receptor degradation and production rate constants. In the anterior part of the striatum, chronic estradiol treatment did not affect the recovery parameters of D1 receptors, whereas lowered receptor degradation and production rate constants were observed in the middle and posterior parts. D1 receptor recovery parameters in the substantia nigra were not affected by chronic estradiol treatment. After EEDQ administration to vehicle-treated rats, striatal dopamine levels decreased gradually, to reach a minimum 4 days later, and returned to control values after 7 days. In estradiol-treated rats, however, dopamine levels increased 2 days after EEDQ. Levels of the dopamine metabolites dihydroxyphenylacetic acid and homovanillic acid increased in the striatum after EEDQ administration in vehicle-treated rats. Even greater increases that lasted longer were observed in estradiol-treated rats after EEDQ. Striatal levels of serotonin and its metabolite 5-hydroxyindoleacetic acid were not significantly affected by EEDQ or estradiol administration. In summary, estradiol decreased striatal D1 and D2 receptor degradation rate constants, with the greatest effect being observed in the caudal part of the striatum. EEDQ dopamine receptor inactivation also revealed an increase of dopamine and its metabolites in the striatum after estradiol treatment.

Adrenergic alpha-Antagonists↗

PubMed1992

Levodopa-induced dyskinesia: facts and fancy. What does the MPTP monkey model tell us?

Levodopa-induced dyskinesia, one of the most frequent long-term side effects of antiparkinsonian therapy, is often attributed to denervation supersensitivity of dopamine receptors and perhaps more specifically the D-1 receptor. The available evidence based not only on clinico-pathological studies in patients but also on results of experiments performed on methyl-phenyl-tetrahydropyridine (MPTP)-treated monkeys suggests that the mechanisms may be more complex than heretofore believed. Thus it appears that no single receptor is the sole culprit, that some form of denervation supersensitivity is probably involved but not in the form of increased density of dopamine receptors. Moreover, other neurotransmitter systems must be considered such as GABA, excitatory aminoacids and peptides. The MPTP monkey model remains very useful for predicting the potential of new drugs for inducing dyskinesia. Such trials however must be performed in drug-naive animals.

Animals↗

PubMed1991

Modulation of dopamine receptor agonist binding sites by cations and estradiol in intact pituitary and 7315a tumors.

The effects of Na+, K+, Mg2+ and Ca2+ on the agonist binding sites of D2 dopamine (DA) receptors were studied in 7315a pituitary tumors. The agonist high and low affinity states of the D2 receptors were investigated with apomorphine competition for [3H]spiperone binding at 25 degrees. In the tumor, all cations markedly increased the affinity of the high affinity binding site, while the affinity of the low affinity binding site was increased only by Na+. The proportion of high to low affinity states was not affected significantly by K+ and Ca2+, whereas it was decreased by Na+ and increased by Mg2+; none of these cations affected the total density of the D2 receptors. The in vitro regulation of D2 receptors by 17 beta-estradiol (E2) was next studied in 7315a tumors and bovine intact adenohypophysis. In intact anterior pituitary, a partial conversion of the high to the low affinity state was obtained in the presence of GTP, while in tumoral pituitary, a complete conversion was observed. Addition of 1 nM E2 to the in vitro incubation mixture prevented these conversions and resulted in a partial return of the high affinity state of the D2 receptors to their control values in both normal and tumoral pituitary. In another experiment, using increasing concentrations of E2 (0.01 to 100 nM) and GTP (10(-8) to 10(-3) nM) on [3H]n-propylnorapomorphine [( 3H]NPA) binding to the D2 receptors in bovine intact adenohypophysis, 1 and 10 nM E2 doubled the IC50 of GTP to decrease [3H]NPA binding. The results show that agonist high and low affinity states of D2 receptors in 7315a tumors are regulated normally by cations. In addition, E2 inhibited the effect of GTP on the agonist sites of the D2 receptors in both intact anterior pituitary tissue and 7315a tumors.

Animals↗

PubMed1991

Regional changes of striatal dopamine receptors following denervation by 6-hydroxydopamine and fetal mesencephalic grafts in the rat.

Young adult female rats received a 6-hydroxydopamine lesion in the left substantia nigra and, 3 weeks later, some of them were grafted with a cell suspension from the ventral mesencephalon of rat embryos (14-15 days old). Six months after transplantation, some grafted rats, following injection of amphetamine, had switched to turning only toward the intact side (type 1), whereas others turned toward the intact side only during the first half of the test (type 2). Levels of dopamine, dihydroxyphenylacetic acid and homovanillic acid were, respectively, 2%, 15% and 35% of the intact side in the denervated striatum of 6-hydroxydopamine rats. Dopamine concentrations were restored to 13% and 10% of the intact side in the grafted striatum of type 1 and type 2 animals, respectively. Levels of homovanillic acid were unchanged following grafts whereas those of dihydroxyphenylacetic acid increased by 209% and 247% in the grafted striatum of type 1 and type 2 animals, respectively. The ratios of dihydroxyphenylacetic acid/dopamine as well as homovanillic acid/dopamine were low in the intact striatum whereas they increased in the denervated striatum with or without graft. The tyrosine hydroxylase immunoreactivity decreased by about 80% in the denervated striatum of 6-hydroxydopamine rats. In type 1 rats, tyrosine hydroxylase immunoreactivity revealed that the graft was localized in the dorsomedial part of the denervated striatum, whereas in type 2 animals, it was also in the medial striatum but it overlapped the dorsal and ventral parts of it equally. D1 as well as D2 dopamine receptors were measured throughout the striatum (9.0-7.6 rostral-caudal coordinates), by autoradiography, using [3H]SCH 23390 (D1 antagonist) and [3H]spiperone (D2 antagonist) binding. Supersensitive D2 receptors were normalized in the dorso- and ventromedial parts of the grafted striatum. D2 receptor density was higher in type 2 than in type 1 rats, more specifically at 8.6-8.2 rostral-caudal coordinates, where the graft was. D1 receptor supersensitivity was modest compared to D2 receptors in the striatum of 6-hydroxydopamine rats and decreased following grafts. DA receptors changes in the striatum, following fetal mesencephalic grafts, may explain the behavioral recovery seen in grafted rats.

Amphetamine↗

PubMed1991

Decrease of behavioral and biochemical denervation supersensitivity of rat striatum by nigral transplants.

The effect of fetal mesencephalic transplants on dopamine receptor supersensitivity has been studied behaviorally and biochemically in rats with a unilateral lesion of the nigrostriatal pathway. Female rats were lesioned with 6-hydroxydopamine in the left substantia nigra. At least one month later they were tested with apomorphine (0.25 mg/kg, s.c.), amphetamine (5 mg/kg, s.c.), LY 171555 (D2 agonist) (0.5 mg/kg, i.p.) and CY 208243 (D1 agonist) (0.5 mg/kg, s.c.). A suspension containing approximately 1.5 x 10(6) cells from the ventral mesencephalon of rat embryos was distributed in three sites in a triangular fashion in the center of the denervated striatum. Six months later, grafted dopamine neurons reinnervated the medial part of the dorsal striatum, increased the dopamine level and reversed the rotational asymmetry evoked by amphetamine. Apomorphine given four months post-transplant still elicited contraversive circling but the number of turns was reduced. Circling evoked six months post-transplant by CY 208243 or LY 171555 was significantly less in grafted rats than in lesioned non-grafted rats. The density of dopaminergic receptors in the striatum of grafted and lesioned rats was examined by autoradiography by means of in vitro binding with [3H]SCH 23390 for D1 receptors and [3H] spiperone for D2 receptors. The results show that intrastriatal nigral transplants decrease the supersensitivity of the D2 receptors and to a lesser extent of the D1 receptors. Normalization of D2 receptors may explain the decrease of behavioral supersensitivity following administration of apomorphine and D2 agonist in grafted rats. D1 receptors were less affected by the lesion and also less normalized than D2 receptors by the transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Dopamine receptor reappearance after irreversible receptor blockade: effect of chronic estradiol treatment of ovariectomized rats.

It is well established that estrogen modulates central dopamine functions; however, the mechanism of this interaction is still poorly understood. We have used peripheral N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) administration to induce irreversible blockade of dopamine receptors in ovariectomized female rats, which were pretreated with estradiol (10 micrograms, twice each day for 2 weeks) or its vehicle, in order to investigate the effect of estradiol on dopamine receptor repopulation kinetics. As previously observed, chronic estradiol treatment increased both striatal D1 and D2 dopamine receptor densities and left affinities unchanged. Anterior pituitary D2 dopamine receptor density remained unchanged. One day after EEDQ administration, a similar decrease (80%) of [3H]SCH 23390 and [3H]spiperone binding to striatum of estradiol- and vehicle-treated animals was observed. Anterior pituitary D2 dopamine receptor specific binding was reduced by about 50% the day after EEDQ. Recovery after EEDQ administration showed that both receptor production rate and degradation rate constants of anterior pituitary D2 and striatal D1 receptors were slowed after chronic estradiol treatment, whereas recovery rates for striatal D2 dopamine receptors were unaffected. EEDQ administration in vehicle-treated rats did not significantly affect plasma prolactin levels, whereas the combination of estradiol pretreatment and EEDQ administration led to increased plasma prolactin levels, compared with estradiol-treated animals that did not receive EEDQ. This suggests that only a fraction of anterior pituitary dopamine receptors are required for a maximal inhibition of prolactin secretion. Estradiol affected both striatal D1 and D2 dopamine receptor densities but only D1 dopamine receptor repopulation kinetics, suggesting that it may act by different mechanisms on each dopamine receptor. Alternatively, estradiol may affect dopamine receptor interaction. Thus, the present study raises the possibility that a biochemical D1/D2 receptor interaction affects dopamine receptor biosynthesis, turnover, and/or gene expression and that estradiol may influence this dopamine receptor interaction in the striatum.

Adrenergic alpha-Antagonists↗

PubMed1990

Modulation of dopamine receptors by cations in 7315a, MtTW15 and estradiol-induced pituitary tumors.

Modulation of dopamine (DA) receptors by cations (Na+, K+, Mg2+, Ca2+) was compared in 7315a, MtTW15, and estradiol valerate-induced (EV-T) pituitary tumors, and intact adenohypophysis. In 7315a tumors, the affinity of [3H]spiperone binding measured at 25 degrees remained unchanged in the presence of each cation individually or all these cations together (IONS) compared to the affinity obtained using a buffer without ions; the density (Bmax) was not affected by monovalent cations or Mg2+ and was decreased by Ca2+ or IONS. When binding experiments were done at 37 degrees, monovalent cations increased affinity whereas divalent cations or IONS did not modify it, and none of these cations affected Bmax values. In MtTW15 tumors, the affinity of [3H]spiperone binding measured at 25 degrees was not changed by Na+ or IONS and was decreased by K+ or divalent cations; the density was decreased by K+ and unchanged by all the other cations. When binding experiments were done at 37 degrees, Na+ increased the affinity, whereas all the other cations did not affect it: the density was unaffected by all the cations studied. In EV-T assayed at 37 degrees, the affinity was increased by monovalent cations or Mg2+ and was unchanged by Ca2+; monovalent cations did not affect the density of [3H]spiperone binding and divalent cations increased it. In binding experiments performed at 25 degrees and 37 degrees, choline chloride did not change the affinity or the density of [3H]spiperone binding to DA receptors in the three pituitary tumors investigated, suggesting that the effect of cations was specific and not due to differences in ionic strength. In the rat normal anterior pituitary, Na+ increased the affinity of [3H]spiperone for the DA receptors, whereas the affinity was unchanged by Ca2+; the density of [3H]spiperone binding was unaffected by these cations. Our results suggest that DA receptors in 7315a and MtTW15 tumors are regulated abnormally by sodium, potassium, magnesium and calcium. In contrast, DA receptors in EV-T are regulated normally by monovalent cations and abnormally by divalent cations as compared to these receptors in intact pituitary tissue.

Animals↗

PubMed1990

Effects of chronic treatment of MPTP monkeys with bromocriptine alone or in combination with SKF 38393.

Eight monkeys developed a severe parkinsonian syndrome after i.v. administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Treatment with bromocriptine (5 mg/kg) relieved the parkinsonian symptoms, but the efficacy of this treatment appeared to decrease slightly with time. The addition of SKF38393 (5 mg/kg) to the bromocriptine treatment in four monkeys prevented and even reversed the tendency to decreased efficacy with an increased response in three out of four animals. Neither of these two treatments induced dyskinesia in these monkeys. Dopamine D1 and D2 receptors, assayed in the caudate nucleus, the putamen and nucleus accumbens with [3H]SCH 23390 and [3H]spiperone binding respectively, were not significantly different in MPTP monkeys treated with bromocriptine or with bromocriptine plus SKF38393. Monkeys in the two treatment groups had a similar extent of denervation of the striatum and accumbens as assessed by the content of dopamine and its metabolites. These results suggest that in MPTP monkeys, the behavioral response to the D2 agonist bromocriptine can be enhanced by concomitant activation of the D1 receptors while this combination of agonists does not induce dyskinesia. The addition of the D1 agonist does not appear to cause further alteration of the D1 or D2 receptors.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1990

Effect of chronic treatment of MPTP monkeys with dopamine D-1 and/or D-2 receptor agonists.

A severe parkinsonian syndrome developed in four monkeys after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). One monkeys subsequently remained untreated, and each of the three others were treated daily for at least one month with Sinemet, bromocriptine or SKF 38393. An intact control monkey (not MPTP-treated) was also included in the experiment. Sinemet and bromocriptine relieved the parkinsonian symptoms, whereas SKF 38393 was ineffective. The animal treated with Sinemet developed dyskinesia while those treated with bromocriptine or SKF 38393 did not. MPTP decreased dopamine levels by more than 99% in the striatum of all monkeys. Striatal D-1 and D-2 dopamine receptor densities as evaluated by autoradiography of [3H]SCH 23390 and [3H]spiperone binding were increased by 66 and 51%, respectively, after MPTP. Sinemet, bromocriptine or SKF 38393 treatment decreased D-2 receptor density, respectively, by 17, 84 and 35% and D-1 receptor density by 28, 33 and 6% vs. that in MPTP-treated animals. Our results suggest that dopamine receptor changes could be implicated in the loss of efficacy and in the side-effects of these treatments.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1990

Effect of the rat estrous cycle at ovariectomy on striatal D-1 dopamine receptors.

We have investigated the effect of the surgical suppression of gonadal steroid hormones by ovariectomy on striatal D-1 dopamine (DA) receptors, in relation with the stage of the estrous cycle at the time of surgery. Plasma levels of 17 beta-estradiol and progesterone declined rapidly to a minimum one and two days after ovariectomy, respectively. Ovariectomy of female rats in proestrus led to an increased density of striatal D-1 DA from the first to the fourth day following surgery with a return to control values on the 7th day. Rats ovariectomized (OVX) in estrus showed an increased striatal D-1 DA receptor density from the second to the fourth day following surgery with a return to control values 7 days following ovariectomy. Striatal D-1 DA receptor density of rats OVX in diestrus remained constant up to 7 days after surgery. The affinity of striatal D-1 DA receptors remained unchanged in all cases. Therefore, this report illustrates that steroid hormonal fluctuations as occurring during the 4-day estrous cycle of the rat can modulate striatal D-1 DA receptors.

Animals↗

PubMed1990

Effect of estradiol and progesterone on rat striatal dopamine uptake sites.

Striatal dopamine (DA) uptake sites labelled with [3H]GBR-12935 binding were investigated in ovariectomized (OVX) rats acutely treated with 17 beta-estradiol (E2) or progesterone (P). One injection of E2 (100 ng, SC) to OVX rats increased plasma levels of this steroid after 15 min while plasma prolactin (PRL) levels remained unchanged. The E2 injection left striatal [3H]GBR-12935 binding affinity unchanged while the maximum density increased 15 and 30 min after the injection (+24% and +18%, respectively). One injection of P (110 micrograms, SC) to OVX rats increased this steroid plasma level from 15 to 120 min while plasma PRL levels remained unchanged. [3H]GBR-12935 binding density and affinity remained unchanged up to 120 min after the injection. Thus, acutely, E2 but not P, modulated striatal DA uptake sites in OVX rats. The effect of E2 appeared in coincidence with the peak of this steroid plasma concentration. This increase was rapid and is probably nongenomic and suggests a causal effect relationship as well as a presynaptic site of action of E2.

Animals↗

PubMed1990

A physiological dose of estradiol with progesterone affects striatum biogenic amines.

The acute effect of estradiol and progesterone on dopamine and serotonin metabolism in rat striatum was studied. One subcutaneous injection of 17 beta-estradiol (300 ng) and progesterone (150 micrograms) into intact male rats increased plasma levels of these steroids, while testosterone, corticosterone, and estrone remained unchanged. Dehydroepiandrosterone, androstane-3 beta, 17 beta-diol and dihydrotestosterone remained undetectably low. Prolactin decreased and androstane-3 alpha, 17 beta-diol, and 17-OH progesterone increased, but less than estradiol and progesterone. Peak levels of striatal dopamine, dihydroxyphenylacetic acid, and homovanillic acid were observed 15-45 min after steroid injection with a return to control values after 45-60 min, while serotonin and 5-hydroxyindoleacetic acid levels were slightly decreased. An injection of estradiol (70 ng) with progesterone (70 micrograms) to ovariectomized female rats left plasma prolactin levels unchanged, while striatum dopamine and serotonin as well as their metabolite concentrations peaked 15-60 min after steroid injection and returned to control values after 45-75 min. To allow for a better comparison of the action of these steroids, the effect of estradiol or progesterone alone and in combination on the brain of ovariectomized rats was compared in the same experiment. A similar increase in metabolites of dopamine levels was observed after these steroids alone or in combination, while dopamine levels were increased only after progesterone alone or in combination with estradiol. An injection of estradiol or progesterone to ovariectomized rats led to peak steroid concentrations at approximately the same time in the brain and plasma. In addition, plasma and brain steroid levels were significantly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Decreased dopamine in the retinas of patients with Parkinson's disease.

Dopamine and it metabolites dihydroxyphenylacetic acid and homovanillic acid were measured in the retinas of eight patients with Parkinson's disease who died. They were divided into two groups according to their last dose of levodopa therapy. One group of three patients had not received levodopa therapy for at least 5 days before death, and the other group of five patients had received therapy 2-15 hours before death. Each patient was matched with controls for delay between death and freezing. In the three patients without levodopa therapy, the retinal dopamine content was lower than normal. In the five patients who received levodopa therapy before death, the retinal dopamine content was similar to that in the controls. This study is the first direct evidence to the authors' knowledge that retinal dopamine concentration is decreased in Parkinson's disease, as it is in the nigrostriatal pathway.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1989

Retinal dopamine sensitivity to MPP+ toxicity: electrophysiological and biochemical evaluation.

This study concerns the effect of intravitreal injection of 1-methyl-4-phenylpyridinium ion (MPP+) on the electroretinograms (ERG) and on the levels of retinal dopamine (DA) in rabbits. The right eye was injected intravitreously with MPP+ while the other received only the vehicle and served as control. The administration of 7, 40, 70 or 700 micrograms MPP+ resulted in a dose-related decrease of the amplitude of the a and b-waves as well as the oscillatory potentials (OPs) of the ERG, down to extinction. In contrast, the retinal DA content was decreased only with the 700 micrograms MPP+ dose. Fluorescein angiography demonstrated abnormalities in the retinal circulation of all MPP+-treated eyes. These observations indicate that MPP+ causes lesions to the retinal vessels at doses non-toxic to the retinal dopaminergic neurons. These data suggest that intravitreal injection of MPP+ cannot be used to study the physiological role of retinal DA.

1-Methyl-4-phenylpyridinium↗

PubMed1989

Striatal D1 dopamine receptor density fluctuates during the rat estrous cycle.

Striatal D1 dopamine (DA) antagonist binding sites were investigated in intact female and male rats, ovariectomized (OVX) animals and during the 4-day estrous cycle. The affinity of the striatal D1 receptor as labelled with [3H]SCH 23390 remains unchanged in intact male, female rats during the estrous cycle and OVX animals. By contrast, ovariectomy decreased striatal D1 receptor density by 17% (P less than 0.01) compared to intact female rats while a small but significant higher density was observed in intact male compared to female rats (10% higher, P less than 0.05). The density of striatal D1 DA receptor was higher on the day of diestrus I (DI) and diestrus II (DII) (P less than 0.01 vs OVX) and fluctuates throughout the estrous cycle with a maximum on the day of DII (P less than 0.05 vs proestrus PM). Our results show for the first time that striatal D1 DA receptors fluctuate during the estrous cycle and can be modulated by gonadal steroids.

Animals↗