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D Lévesque

Publications and source records attributed to D Lévesque.

At least 37 records · Page 2Linked to original sources
PubMed1997

Dopamine D3 receptor antisense reduces neuropeptide mRNA levels in rat nucleus accumbens.

We have investigated the effects of a dopamine D3 receptor antisense oligodeoxynucleotide (ODN), on neurotensin and dynorphin mRNA levels in rat nucleus accumbens. Intracerebroventricular injections of ODNs were made into the lateral ventricle (5 and 10 microg h(-1), for 5 days). Receptor autoradiography of dopamine D2 and D3 receptor subtypes was performed. Dynorphin and neurotensin mRNA levels were evaluated by in situ hybridization. Dopamine D3 receptor levels were significantly decreased in nucleus accumbens shell (NAS) of rats that received the D3 antisense ODN. Dynorphin and neurotensin mRNA levels were also significantly decreased in the NAS after D3 antisense ODN treatments. Our results show that D3 receptors may regulate neuropeptide gene expression and demonstrate that an antisense strategy could be useful to identify molecular targets under control of specific dopamine receptor subtypes.

Animals↗
PubMed1996

Aminotetralin drugs and D3 receptor functions. What may partially selective D3 receptor ligands tell us about dopamine D3 receptor functions?

The dopamine D3 receptor gene was identified by Sokoloff and colleagues in 1990. This finding rapidly gained the interest of the scientific community because this unexpected dopamine receptor subtype may play an important role in the antipsychotic activity of neuroleptic drugs. It recognizes most neuroleptics with a high affinity, and its brain distribution is restricted mainly to the ventral part of the striatal complex. However, the characterization and the subsequent identification of functions of the D3 receptor were hampered initially by at least four important factors that are still partially unresolved: (1) the absence of selective drugs that can discriminate between the D2 and D3 receptor subtype functions in vivo, (2) the lack of apparent coupling with GTP-dependent proteins, (3) the absence of effects on second messenger systems, and (4) the low level of expression of this receptor in brain tissue; these factors have contributed to tempering the interest of scientists. However, this situation has begun to change with the identification of [3H]7-hydroxy-N,N-(di-n-propyl)-2-aminotetralin ([3H]7-OH-DPAT), the first selective ligand for the dopamine D3 receptor. Although its binding selectivity for the D3 versus the D2 receptor is somewhat artificial, the potentially important impact of identification of a function for the D3 receptor encouraged scientists to use this aminotetralin compound for in vivo studies with, however, limited success. This commentary is focused on the impact and controversies generated by the use of 7-OH-DPAT and its congeners, on new conceptual views that may arise from this research, and on what partially selective D3 receptor ligands may tell us about dopamine D3 receptor functions.

Animals↗
PubMed1995

A paradoxical regulation of the dopamine D3 receptor expression suggests the involvement of an anterograde factor from dopamine neurons.

The effects of interruption of dopaminergic transmission or sustained blockade of dopamine receptors by neuroleptics on the dopamine D3 receptor in the shell of the nucleus accumbens were investigated in rats. In this brain area the D3 receptor is abundant and may mediate antipsychotic drug effects. The D3 receptor density and mRNA abundance were evaluated with 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin and by quantitative PCR or image analysis of in situ hybridization signals, respectively. Unilateral dopamine neuron degeneration by 6-hydroxydopamine or sections triggered, after a few days, a marked decrease (up to 50%) in D3 receptor binding and mRNA in the nucleus accumbens. In contrast, a 2-week treatment with the neuroleptic haloperidol (20 mg/kg) had no effect on D3 receptor density and mRNA but enhanced D2 receptor density and mRNA level by > 50%. In addition, tolerance to the haloperidol-induced change of neurotensin mRNA mediated by the D2 receptor developed, but there was no tolerance to the opposite change mediated by the D3 receptor. Reserpine, a monoamine-depleting drug with antipsychotic activity, did not modify D3 receptor mRNA. These observations reinforce the idea that the D3 receptor may be an important target for neuroleptics whose antipsychotic actions, but not extrapyramidal motor actions, do not display tolerance. The D3 receptor mRNA level was also decreased by a unilateral injection in dopamine cell body areas of colchicine, a drug blocking the anterograde axonal transport, or by baclofen, a type A gamma-aminobutyric acid receptor agonist reducing dopamine neuron activity, but not by sustained blockade of D1-like and D2-like, neurotensin, or cholecystokinin receptors. We therefore propose that an anterograde factor present in mesolimbic dopaminergic neurons, but distinct from dopamine and known peptide cotransmitters, plays a positive role on transcription of the D3 receptor gene.

Animals↗
PubMed1995

A functional test identifies dopamine agonists selective for D3 versus D2 receptors.

The functional potency of a series of dopamine agonists for increasing mitogenesis, measured by incorporation of [3H]thymidine, was established in transfected cell lines expressing human D2 or D3 receptors. The functional selectivity of agonists markedly differs from their binding selectivity. (+)7-OH-DPAT, pramipexole, quinerolane and PD 128,907, the most D3 receptor-selective compounds in binding studies, were 7, 15, 21 and 54 times more potent, respectively, at the D3 than at the D2 receptor in the functional test. Bromocriptine displayed a 10-fold functional selectivity toward the D2 receptor. The known behavioural actions of D3 selective agonists support a role for the D3 receptor in motor inhibitions, which should be taken into account for the treatment of motor dysfunctions by dopamine agonists.

Animals↗
PubMed1995

Phenotypical characterization of neurons expressing the dopamine D3 receptor in the rat brain.

We have established the cellular distribution of the dopamine D3 receptor using tritiated 7-hydroxy-N-N-di-n-propyl-2-aminotetralin and a complementary RNA probe to visualize autoradiographically the protein in binding studies and the gene transcripts by in situ hybridization, respectively. Studies with these two markers confirm the restricted expression of the D3 receptor in few brain areas, i.e. mainly the ventral striatal complex, the substantia nigra-ventral tegmental area and the cerebellum. In nucleus accumbens, the D3 receptor was mainly expressed in medium-sized neurons of the rostral pole and ventromedial shell subdivisions, but not of the core or septal pole, i.e. accumbal subdivisions expressing the D2 receptor. In the ventromedial shell, about 60% of the D3 receptor-expressing neurons were neurotensin neurons, presumably projecting to the ventral pallidum. In the islands of Calleja, both D3 receptor binding and messenger RNA were abundant in the entire population of granule cells. These cells are known to make sparse contacts with dopaminergic axons and also to express the D1 receptor. In the mesencephalon, low levels of D3 messenger RNA were detected in few dopamine neurons of substantia nigra pars lateralis and ventral tegmental area. In addition, some D3 receptor binding but not messenger RNA was detected in medial substantia nigra and lateral ventral tegmental area, where the receptor is presumably located presynaptically on afferents. In the archicerebellum, Purkinje cell perikarya in lobules 9 and 10 expressed the D3 receptor messenger RNA, whereas binding sites were found in the molecular layer, where corresponding dendrites but no known dopaminergic projection from mesencephalon are found. The occurrence of D3 receptor gene expression in some brain areas receiving low dopamine innervation supports the hypothesis that this receptor may mediate non-synaptic actions of dopamine.

Animals↗
PubMed1995

The dopamine D3 receptor and schizophrenia: pharmacological, anatomical and genetic approaches.

Antipsychotic drug therapy mainly rests on the use of antagonists of dopamine D2-like (D2, D3 and D4) receptors, for which all clinically active compounds have high affinity. The D3 receptor has a restricted expression in brain limbic areas, associated with cognitive functions and motivated behavior. D3 selective agonists and antagonists reveal an inhibitory role on motor behaviors for the D3 receptor, opposite to that of the D2 receptor. An opposing role for D2 and D3 receptors is also suggested by the contrasted effects of D2/D3 antagonists on neurotensin expression in discrete subdivisions of nucleus accumbens, where D2 and D3 receptors are selectively expressed. Tolerance to the motor but not to the therapeutic effects of neuroleptics is observed after repeated administration, which upregulates the D2, but not the D3 receptor in animals. In genetic association studies, an excess of homozygosity for both alleles of the BalI polymorphism at the D3 receptor gene was found in schizophrenic patients, suggesting that this gene may have subtle influence on the liability to develop schizophrenia. These results suggest the D3 receptor as an important target for antipsychotic drug action, and D3 receptor selective antagonists as promising therapeutic agents.

Animals↗
PubMed1994

Opposing roles for dopamine D2 and D3 receptors on neurotensin mRNA expression in nucleus accumbens.

Using in situ hybridization histochemistry in rat nucleus accumbens, we show that the dopamine D3 receptor mRNA is expressed in the ventromedial part of the shell subdivision, where its gross distribution matches that of neurotensin mRNA. In addition, hybridization studies at the cellular level show that a large fraction of the neurotensin neurons co-express the D3 receptor mRNA in this restricted area. In contrast, the dopamine D2 receptor mRNA is expressed mainly in the core and marginally in the shell, at the level of the cone. In rats treated by haloperidol and sulpiride, two D2-like receptor antagonists, but not by SCH 23390, a D1-like receptor antagonist, proneurotensin mRNA was increased in the D2 receptor mRNA-rich areas but decreased in the D3 receptor mRNA-rich areas. This suggests that the D2 and D3 receptors control neurotensin mRNA expression negatively and positively, respectively.

Animals↗
PubMed1994

Functional coupling of the human dopamine D3 receptor in a transfected NG 108-15 neuroblastoma-glioma hybrid cell line.

Transfection of a human dopamine D3 receptor cDNA in a neuroblastoma-glioma hybrid cell line (NG 108-15) provided clonal cell lines stably expressing up to 600 fmol per mg protein of [125I]iodosulpiride binding sites. Dopamine and several agonists distinguished two receptor-affinity states in membranes. In the case of dopamine, the high-affinity state (Ki = 0.9 nM, 30% of total binding) was completely converted into a low-affinity state (Ki = 57 nM) in the presence of 10 microM guanosine-5'-O-(3-thiotriphosphate). In addition to these two sites, a site with a very low affinity for dopamine was evidenced in whole cells. The dopamine D3 receptor mediated two responses: c-fos activation, as measured by the appearance of Fos-like immunoreactivity, and increased mitogenesis, as measured by incorporation of [3H]thymidine. The Fos-like immunoreactivity appeared within 30 min, lasted 2 h and was blocked by the partially selective dopamine D3 receptor compound (+)-UH 232 (cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin). The mitogenic effect, which occurred after a lag time (over 2 h stimulation), was produced with subnanomolar potency and full intrinsic activity by several compounds previously identified as dopamine D2 receptor agonists, e.g. quinpirole, (+)-7-OH-DPAT ((+)-7-hydroxy-2-(di-n-propylamino)tetralin) and RU 24926 (N-n-propyl-di-beta(3-hydroxyphenyl)-ethylamine), and was reversibly blocked by (+)-UH 232 (Ki = 9 nM). Talipexole (B-HT 920, 5-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepin) was identified as a partial agonist at the dopamine D3 receptor. Dopamine D3 receptor-mediated mitogenesis was potentiated by a phorbol ester and was abolished by pretreatment with pertussis toxin. A mitogenic effect of same amplitude was elicited by bradykinin or carbachol, both acting through constitutive receptors. Bradykinin markedly activated inositol phosphate turnover, and had no effect on forskolin-stimulated cyclic AMP accumulation. Carbachol inhibited forskolin-stimulated cyclic AMP accumulation and had no effect on inositol-phosphate turnover. Quinpirole had no effect on any of these second messenger pathways. Thus, in transfected NG 108-15 cells, the dopamine D3 receptor is coupled to a pertussis toxin-sensitive G protein and mediates two possibly unrelated biological effects, through initial biochemical events that remain to be identified.

Animals↗
PubMed1993

Modulation by estradiol and progesterone of the GTP effect on striatal D-2 dopamine receptors.

Agonist binding properties of rat striatal D-2 dopamine (DA) receptors were investigated after in vivo or in vitro estradiol or progesterone exposures in order to elucidate the mechanism of action of steroid hormones on DA receptors. Chronic estradiol treatment of ovariectomized rats (10 micrograms, twice each day, for 2 weeks) increased lateral striatum total receptor density and left unchanged the proportion and affinity of the agonist high- and low-affinity states of this receptor in the striatum. In addition, when GTP was added in DA competition for [3H]spiperone binding experiments, D-2 receptors in the medial part of the striatum from estrogen-treated animals were more sensitive to GTP than those in the lateral part, whereas GTP had equal activity in both parts of the striatum in vehicle-treated rats. With apomorphine, but not with DA competition for [3H]spiperone binding, addition of estradiol (1 nM) to striatal homogenates of intact male rats prevented the expected shift of the high- to the low-affinity state of D-2 receptors, normally induced by GTP (100 microM) under these conditions. This effect of estradiol was not observed in the presence of 4 mM MgCl2, while in vitro progesterone (100 nM) had no effect in either the absence or presence of MgCl2. In addition, in vivo chronic progesterone treatment of ovariectomized rats left striatal [3H]spiperone density and affinity unchanged. Moreover, 1 nM estradiol increased the IC50 of GTP for inhibition of [3H]N-propylnorapomorphine binding to the high-affinity state of striatal D-2 receptors. This effect was also observed but decreased by 2-fold in the presence of MgCl2. Our data suggest that estradiol in vivo and in vitro interferes with the effect of GTP on striatal D-2 DA receptors.

Animals↗
PubMed1993

Study of the clinical utility of radioreceptor assay in outpatients with schizophrenia receiving high doses of neuroleptics.

A radioreceptor assay (RRA) was used to determine the neuroleptic plasma levels of 32 outpatients with schizophrenia receiving a high dose of neuroleptics (the equivalent of 18 mg or more of oral haloperidol per day) and undergoing a 50% partial and progressive reduction (ten percent each month for five months) in their medication. Plasma levels of neuroleptics were measured three times: before (T1) and immediately after the 50% reduction (T2) and five months later (T3). A linear correlation was observed between neuroleptic plasma levels obtained by RRA and the neuroleptic doses prescribed at T1 and T3. Furthermore, neuroleptic plasma levels were significantly lower at T3 than at T1. Concurrent evaluations of psychopathology were done using the Brief Psychiatric Rating Scale, and the results indicated that no correlation exists between neuroleptic plasma levels and the total rating scale scores at T1 but a significant correlation was observed at T3.

Adult↗
PubMed1992

Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin.

We have identified 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin ([3H]7-OH-DPAT) as a selective probe for the recently cloned dopamine D3 receptor and used it to assess the presence of this receptor and establish its distribution and properties in brain. In transfected Chinese hamster ovary (CHO) cells, it binds to D3 receptors with subnanomolar affinity, whereas its affinity is approximately 100-, 1000-, and 10,000-fold lower at D2, D4, and D1 receptors, respectively. Specific [3H]7-OH-DPAT binding sites, with a Kd of 0.8 nM and a pharmacology similar to those at reference D3 receptors of CHO cells, were identified in rat brain. D3 receptors differ from D2 receptors in brain by their lower abundance (2 orders of magnitude) and distribution, restricted to a few mainly phylogenetically ancient areas--e.g., paleostriatum and archicerebellum--as evidenced by membrane binding are autoradiography studies. Native D3 receptors in brain are characterized by an unusually high nanomolar affinity for dopamine and a low modulatory influence of guanyl nucleotides on agonist binding. These various features suggest that D3 receptors are involved in a peculiar mode of neurotransmission in a restricted subpopulation of dopamine neurons.

Animals↗
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

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↗
PubMed1991

Psychopharmacological evidence for a role of the ATP-sensitive potassium channel in the substantia nigra of the rat.

Recent evidence suggests that an ATP-sensitive potassium channel is present in the brain. From ligand binding studies it has been inferred that this relatively unfamiliar channel is particularly densely distributed in areas associated with motor control. The aim of this study was thus to examine whether pharmacological agents, specific for the ATP-sensitive channel in other tissues, had effects on a particular motor behaviour associated with the substantia nigra: the effects of microinfusion into the substantia nigra of diverse potassium channel blocking agents were examined on the initiation of circling behaviour in the normal rat. Application of tolbutamide and quinine, but not tetraethylammonium, caused circling behaviour in the presence of a systemically administered challenge of amphetamine. However, in the case of application of tolbutamide, the direction of circling was dependent on whether the site of infusion was in the pars compacta or pars reticulata. On the other hand, the effects of quinine were the same, irrespective of site of application within the substantia nigra, i.e. in the same direction, as seen after injection of tolbutamide into the pars compacta. Quinine and tolbutamide are different chemical species which both, unlike tetraethylammonium, principally block the ATP-sensitive potassium channel. It therefore seems that an ATP-sensitive potassium channel in the pars compacta cells of the substantia nigra could play a selective role in modifying the net activity of the nigrostriatal pathway and hence the control of movement.

Adenosine Triphosphate↗
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

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

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↗