SEARCH · PubMed Health

Results for “DOPAMINE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources

PubMed1988

3- and 4-O-sulfoconjugated and methylated dopamine: highly reduced binding affinity to dopamine D2 receptors in rat striatal membranes.

The binding properties of 3- and 4-O-sulfo-conjugated dopamine (DA-3-O-S, DA-4-O-S) as well as 3-O-methylated dopamine (MT) to rat striatal dopamine D2 receptors were investigated. 3H-spiperone was used as a radioligand in the binding studies. In saturation binding experiments (+)butaclamol, which has been reported to bind to dopaminergic D2 and serotoninergic 5HT2 receptors, was used in conjunction with ketanserin and sulpiride, which preferentially label 5HT2 and D2 receptors, respectively, in order to discriminate between 3H-spiperone binding to D2 and to 5HT2 receptors. Under our particular membrane preparation and assay conditions, 3H-spiperone binds to D2 and 5HT2 receptors with a maximal binding capacity (Bmax) of 340 fmol/mg protein in proportions of about 75%:25% with similar dissociation constants KD (35 pmol/l; 43 pmol/l). This result was verified by the biphasic competition curve of ketanserin, which revealed about 20% high (KD = 24 nmol/l) and 80% low (KD = 420 nmol/l) affinity binding sites corresponding to 5HT2 and D2 receptors, respectively. Therefore, all further competition experiments at a tracer concentration of 50 pmol/l were performed in the presence of 0.1 mumol/l ketanserin to mask the 5HT2 receptors. DA competition curves were best fitted assuming two binding sites, with high (KH = 0.12 mumol/l) and low (KL = 18 mumol/l) affinity, present in a ratio of 3:1. The high affinity binding sites were interconvertible by 100 mumol/l guanyl-5-yl imidodiphosphate [Gpp(NH)p], resulting in a homogenous affinity state of DA receptors (KD = 2.8 mumol/l).2+ off

Animals↗

PubMed1976

Differential actions of dopamine agonists and antagonists on the gamma-butyrolactone-induced in mouse brain dopamine.

gamma-Butyrolactone (GBL) increased the dopamine concentration in the forebrain of the mouse. Apomorphine dose-dependently antagonized the GBL effect, while piribedil was less effective. Haloperidol prevented the antagonism of GBL by apomorphine but pimozide was ineffective in blocking apomorphine. After chronic treatment with haloperidol or pimozide, there was no alteration of the maximum GBL-induced increase in dopamine nor was there any significant change in the antagonism by apomorphine, although a trend toward increased sensitivity to apomorphine was noted in the group withdrawn from haloperidol. These results suggest that in the mouse, haloperidol is a more effective antagonist of presynaptic dopamine autoreceptors than pimozide, while apomorphine is a better presynaptic agonist than piribedil.

4-Butyrolactone↗

PubMed1984

Unilateral striatal dopamine denervation: reduced motor inhibitory effects of dopamine antagonists revealed in models of asymmetric and circling behaviour.

Circling and asymmetric behaviours to apomorphine (dopamine agonist/antagonist) challenge were studied in rats with unilateral striatal electrolesions or 6-hydroxydopamine (6-OHDA) lesions, each induced by combined lesions at 3 striatal locations, to allow an assessment of drug action on 'normal' receptors in the intact striatum or 'supersensitive' receptors in the lesioned striatum respectively. The minimally effective dose of 6-OHDA (given in the presence of DMI and tranylcypromine) to cause functional change was 3 X 8 micrograms, with 3 X 32 micrograms providing maximal change. Electrolesions were shown histologically to be confined to striatal tissue, and dopamine depletions caused by 6-OHDA were selective for the striatum. Temporal differences were recorded for onset of asymmetry and circling behaviour, both between behaviours and between lesions. Thus, asymmetry developed during the 2nd-4th days after 6-OHDA lesion but circling developed more abruptly on postoperative days 10-12. In contrast, both asymmetry and circling behaviours were apparent from the first day following electrolesion. The dose-dependent effects of apomorphine were apparent at much lower doses in 6-OHDA lesioned than electrolesioned rats. This potency difference was also demonstrated for two further dopamine agonists, 2-di-n-propylamino-5,6-dihydroxytetralin and SK & F 38393. In contrast, the agonist-induced asymmetric and circling behaviours of electrolesioned rats were some 9-44 times more sensitive than those of 6-OHDA lesioned rats to antagonism by the neuroleptic agents haloperidol, alpha-flupenthixol and oxiperomide, although tiapride antagonism was very similar in both the electrolesioned and 6-OHDA-lesioned rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1983

Failure of 2 Hydroxyestradiol to interact with dopamine inhibition of human prolactin secretion in vitro and with dopamine receptors of prolactin-secreting adenomas.

The ability of 2-Hydroxyestradiol, a catecholestrogen, and 17 beta Estradiol to interact with the dopamine inhibition of prolactin and with dopamine receptors has been tested on dispersed human prolactin-secreting cells obtained from ten pituitary adenomas. There is a 80% inhibition of prolactin secretion obtained by addition of dopamine in a superfusion system. This inhibition is not affected by preexposure to the steroids, or by their introduction into the perifusion medium. Moreover 2 Hydroxyestradiol and 17 beta Estradiol do not interact with the binding of 3H Domperidone to DA receptors.

Adenoma↗

PubMed1988

Acute reduction of dopamine levels alters responses of basal ganglia neurons to selective D-1 and D-2 dopamine receptor stimulation.

Extracellular single unit recording techniques were used to investigate dopamine agonist-induced changes in the tonic activity of globus pallidus neurons in normal control rats, and in rats in which dopamine levels were acutely reduced by alpha-methyl-para-tyrosine (AMPT) pretreatment. Systemic administration of the nonselective D-1/D-2 agonist apomorphine consistently induced large increases in the firing rates of globus pallidus neurons, as shown previously. The D-1 agonist SKF 38393 frequently induced no change in pallidal cell firing rates with doses up to 20 mg/kg; however, firing rates of 40% of the cells were stimulated by more than 20% of baseline and 14% were partially inhibited after 20 mg/kg SKF 38393. Following AMPT pretreatment, SKF 38393 induced only increases and no changes in activity; no decreases were observed. The D-2 agonist quinpirole typically increased pallidal neuron activity in a dose-dependent manner but was markedly less effective at stimulating pallidal neuron activity than apomorphine. In AMPT-treated rats, quinpirole's effects were significantly attenuated. Consistent with previous results, most cells showed large rate increases when SKF 38393 and quinpirole were coadministered to normal rats; these increases were similar in magnitude to those induced by apomorphine. In contrast to the observation that AMPT treatment altered the responses of globus pallidus neurons to individually administered quinpirole and SKF 38393, neither the increases in pallidal cell activity induced by apomorphine nor those induced by coadministration of SKF 38393 and quinpirole were significantly attenuated in AMPT-treated rats. The results support the idea that stimulation of both D-1 and D-2 receptors appears to be required to induce apomorphine-like changes in basal ganglia output. Moreover, the effects of individually administered D-1 and D-2 agonists observed in normal rats appear to depend upon the degree to which the complementary receptor subtype is stimulated by endogenous dopamine.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1993

Effects of stimulation of dopamine D1 receptors on the cortical EEG in rats: different influences by a blockade of D2 receptors and by an activation of putative dopamine autoreceptors.

The effects of a stimulation of dopamine D1 receptors by using (+/-)SKF 38393 on the cortical EEG in rats which were chronically implanted with electrodes were studied. Administration of SKF 38393 (3 or 9 mg/kg, s.c.) produced alterations suggesting an arousal in the EEG: the power in all of the frequency bands decreased to a level of 70-80% of baseline activity, which effect was dose- and time-dependent. In behaviour, episodes of intensive grooming (face-washing) alternated with those of lack of spontaneous motility and occasionally chewing movements were noted. In contrast, apomorphine (0.5 mg/kg, s.c.) produced a selective increase in power in the alpha 1 band, accompanied by stereotyped sniffing and licking. The effects of SKF 38393 (9 mg/kg) were completely blocked by pretreatment with the selective antagonist at D1 dopamine receptors, SCH 23390 (0.2 mg/kg, i.p.). The application of haloperidol (0.1 mg/kg, i.p.), which is mainly a D2 blocker, failed to influence the alterations induced by SKF 38393 (9 kg/kg, s.c.). In a further experimental group, the effects produced by stimulation of D1 receptors (SKF 38393 9 mg/kg), followed by activation of putative dopamine autoreceptors by a small dose of apomorphine (0.05 mg.kg, s.c.) were studied: in this case, the effects of SKF 38393 were abolished and typical effects of small doses of apomorphine were manifest, such as hypokinesia and sedation, accompanied by large increases of power in all of the frequency bands, except beta 2. The results suggest that stimulation of D1 receptors produces some desynchronization in the EEG.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1989

Inhibition of lipopolysaccharide-induced alpha/beta-interferon synthesis by dopamine and the dopamine-1 agonist fenoldopam.

In vitro incubation of Listeria monocytogenes-immune spleen cells in the presence of dopamine or fenoldopam, a dopamine-1 (D1) agonist, inhibited alpha/beta-interferon (IFN) synthesis induced by the mitogen lipopolysaccharide (LPS), in a manner that appeared to be concentration dependent. In addition, the inhibitory effect of dopamine and fenoldopam on the synthesis of IFN was prevented by incubating immune spleen cells in the presence of haloperidol, a D1 antagonist.

Animals↗

PubMed1995

Dopamine agonists used in the treatment of Parkinson's disease and their selectivity for the D1, D2, and D3 dopamine receptors in human striatum.

1. It has been suggested that an ideal antiparkinsonian treatment requires stimulation of both D1 and D2 dopamine receptors. Bromocriptine and lisuride are regarded as pure D2 receptor agonists, whereas pergolide and apomorphine are thought to stimulate both D1 and D2 receptors. 2. The aim of this study was to compare the affinities of bromocriptine, lisuride, pergolide, and apomorphine for the D1, D2, and D3 receptors in postmortem human striatum. The dissociation constants (Ki values) of the dopamine agonists were determined from competition binding experiments with selective radioligands. 3. The Ki values of the orally administered agonists--bromocriptine, pergolide, and lisuride--for the D2 receptors were proportional to their optimal doses against parkinsonism. Ki(D1)/Ki(D2) ratios were 23 for lisuride, 67 for pergolide, 60 for bromocriptine, and 2.6 for apomorphine. Ki(D3)/Ki(D2) ratios were 0.4 for lisuride, 1 for pergolide, 5.4 for bromocriptine, and 21 for apomorphine. 4. The present results support the hypothesis that the antiparkinsonian effect of dopamine agonists is mediated primarily by D2 receptors. Apomorphine is a mixed D1/D2 agonist, but pergolide has no more D1 agonist properties than bromocriptine and lisuride. The role of the D3 receptors is unknown, but their activation might either be associated with the generation of psychiatric side-effects or dyskinesias, or alternatively add to antiparkinsonian activity.

Aged↗

PubMed1993

Persistent effects of subchronic toluene exposure on spatial learning and memory, dopamine-mediated locomotor activity and dopamine D2 agonist binding in the rat.

The effects of subchronic inhalation exposure to toluene (80 ppm, for 4 weeks, 5 days/week, 6 h/day) was studied on spatial learning (postexposure days 3-6) and memory (postexposure day 14) using a water maze, on spontaneous and apomorphine-induced (1 mg/kg, subcutaneously (s.c.)) locomotor activity (postexposure day 17) and on the binding parameters of the dopamine D2 agonist S(-)[N-propyl-3H(N)]propylnorapomorphine ([H]NPA) in membrane preparations of the neostriatum of the rat. Toluene treatment was found to cause a statistically significant impairment in acquisition and retention of the spatial learning task. Furthermore, toluene significantly increased (2-fold) apomorphine-induced locomotion and caused a trend for a 50-60% increase in motility without any significant effect on rearing. Spontaneous locomotion, motility and rearing were not affected by toluene. Toluene treatment produced a significant 30-40% increase in the Bmax values of [3H]NPA and a trend for a 20-30% increase in the KD values. These results indicate that subchronic exposure to toluene in low concentrations causes a slight but persistent deficit in spatial learning and memory, a persistent increase in dopamine-mediated locomotor activity and an increase in the number of dopamine D2 receptors in the rat.

Administration, Inhalation↗

PubMed1994

Are the dopaminergic cells of the lamprey retina interplexiform cells? A dopamine, tyrosine hydroxylase and dopamine beta-hydroxylase immunocytochemical study.

The distribution of dopaminergic cells in the retina of sea lamprey Petromyzon marinus L. was studied with antisera against dopamine and tyrosine hydroxylase. Both antisera consistently labelled cells and processes located in the inner nuclear and inner plexiform layers. No dopamine-immunoreactive processes were observed in the external retina. The ellipsoids of photoreceptors and small bodies close to the external limiting membrane were also labelled with the tyrosine hydroxylase antiserum. It is concluded that the dopaminergic cells of the lamprey retina are amacrine cells. In addition, the presence of dopamine-beta-hydroxylase-like-immunoreactive fibres of central origin is reported for the first time.

Animals↗

PubMed1994

Prenatal ontogeny of D2 dopamine receptor and dopamine transporter gene expression in the rat mesencephalon.

This work demonstrates the early prenatal expression (by gestational day 14) of dopamine D2 receptor and dopamine transporter mRNAs by immature dopaminergic cells of the rat mesencephalon using in situ hybridization. Our results indicate that mRNAs are detectable 3 days before the appearance of functional D2 presynaptic receptors and detectable dopamine release at striatal terminals.

Animals↗

PubMed2003

Inhibition by arachidonic acid and other fatty acids of dopamine uptake at the human dopamine transporter.

It is known that arachidonic acid, in addition to promoting release of dopamine, can inhibit its transport. The present study provides preliminary information on structure-activity relationships for uptake inhibition by rotating disk voltammetry in human embryonic kidney-293 cells expressing the human dopamine transporter. Except for anandamide, all other fatty acids studied at a pretreatment concentration of 80 microM caused significant reductions in Vmax but not Km. Increasing saturation of the hydrocarbon tails (partial saturation: oleic acid, linoleic acid; full saturation: arachidic acid, stearic acid, stearic acid ethyl ester) removed inhibitory activity incrementally, suggesting a role for cis-unsaturation (folding/bending of hydrocarbon tails). The relative lack of effect of 5,8,11,14-eicosatetraynoic acid also supports the idea that less linear structures are less inhibitory on dopamine uptake. Esterification of the free carboxylic group (arachidonic acid ethyl ester) prevented most of the inhibitory activity, arguing against mere membrane lipid disruption. Finally, the endogenous cannabinoid anandamide greatly reduced uptake Vmax accompanied by a small decrease in Km, a potentially important effect on dopaminergic neurotransmission.

Arachidonic Acid↗

PubMed2000

Dopamine uptake by mouse neuroblastoma N1E-115 cells stably expressing human dopamine transporter is differentially inhibited by anti-idiotypic ab2beta antibodies mimicking the configuration of cocaine.

We have successfully constructed a mouse neuronal N1E-115 cell line stably expressing a fully functional human dopamine transporter (hDAT). Previous studies in our laboratory have produced several anti-idiotypic Ab2beta antibodies that mimic the configuration of the cocaine molecule at their antigen-combining site. In the present study, we observed that some anti-idiotypic Ab2beta antibodies inhibited dopamine uptake by the hDAT-transfected line. Each antibody showed a different level of inhibition (between 40% and 90%). These findings suggest that the internal images of these antibodies can be used as analog peptides that may compete with cocaine for its binding site on the transporter but not impair dopamine uptake as much as cocaine does.

Animals↗

PubMed1998

Effects of dopamine antagonists and accumbens dopamine depletions on time-constrained progressive-ratio performance.

Four experiments were conducted to determine the effects of dopamine (DA) antagonists and DA depletions on progressive-ratio responding for food reinforcement. On this schedule, ratio requirement increased by one response after each reinforcer was obtained, and rats were tested in 30-min sessions. Response rates and highest ratio completed were reduced in a dose-related manner by systemic injections of the D1 antagonist SCH 23390, and also by the D2 antagonists haloperidol and raclopride. Drug-treated rats also showed reductions in time to complete the last ratio, demonstrating that they had stopped responding before the end of the session. DA depletions produced by injections of 6-OHDA directly into the nucleus accumbens substantially decreased both the number of responses and the highest ratio completed. The deficits in response number and highest ratio completed induced by DA depletions persisted through the first 3 weeks of postsurgical testing, with some recovery by the fourth week. However, the deficits resulting from dopamine depletions were largely a manifestation of a decrease in response rate; although time to complete the last ratio was significantly reduced by dopamine depletions in the first few days of testing, rats recovered on this measure by the fifth day after surgery. Although previous work has shown that performance on several schedules (e.g., continuous, low value ratios, variable interval) is relatively unaffected by accumbens DA depletions, the present data demonstrate that such depletions do produce a substantial and persistent impairment of progressive ratio response output. Rats with accumbens DA depletions appear to have deficits in maintaining the high work output necessary for responding at large ratio values. The relative sparing of responding on some simple schedules, together with the present progressive ratio results, suggest that rats with accumbens DA depletions remain directed toward the acquisition and consumption of food, but they show deficits in work output for food.

Animals↗

PubMedDate not supplied

Volume transmission of dopamine may modulate light-adaptive plasticity of horizontal cell dendrites in the recovery phase following dopamine depletion in goldfish retina.

We investigated the recovery of light-adaptive spinule formation following dopamine depletion with intraocular injection of 6-hydroxydopamine (6-OHDA) and subsequent neogeneration of dopamine interplexiform cells (DA-IPC) at the marginal zone. DA-IPCs were gone by 2 weeks postinjection and appeared at the marginal zone by 6 weeks postinjection, at which time DA-IPC neurites grew toward the central retina, reaching within 0.5 mm of the central retina by 1 year. Retinas from day time, light-adapted fish at 2 weeks, 4 weeks, 3 months, and 1 year postinjection with 6-OHDA were processed for pre-embedding tyrosine hydroxylase immunoreactivity (TOH-IR) and compared to sham-injected and control retinas at the electron-microscopical (EM) level. Only 6-OHDA fish that tilted markedly toward the injected eye were used for these experiments. The tilt mimics the dorsal light reaction, indicating a 2-2.5 log unit increase in the photopic sensitivity of the 6-OHDA eye. Spinule formation was reduced by about 60% in the 2- and 4-week 6-OHDA retinas, but returned to control levels throughout the entire retina of 3-month and 1 year 6-OHDA retinas even though the central region of these retinas contained no detectable TOH-IR. Intraocular injection with 10 microM SCH 23390 (a D1 antagonist) reduced light-adaptive spinule formation by 50% both in control eyes as well as those eyes that were 3 months post 6-OHDA injected. The full return of spinule formation with only partial reinnervation of the retina with DA-IPC processes and their subsequent inhibition by SCH 23390 indicates that dopamine diffused large distances within the retina to regulate this synaptic plasticity (i.e. displayed volume transmission). Also, since all 6-OHDA injected fish displayed an increased photopic sensitivity in the injected eye when sacrificed, we suggest that horizontal cell spinules are not required for photopic luminosity coding in the outer retina.

Adaptation, Ocular↗

PubMed2000

Release and elimination of dopamine in vivo in mice lacking the dopamine transporter: functional consequences.

In mice lacking the dopamine transporter (DAT), the amplitude of dopamine (DA) release and the kinetics of dopamine elimination were measured in vivo using carbon fibre electrodes combined with amperometry. DA release was evoked by electrical stimulation of the medial forebrain bundle. The amplitude of DA release per pulse was lower (7% in striatum and 21% in nucleus accumbens) than in wild-type mice. Inhibition of monoamine oxidases (MAOs) by pargyline, but not of catechol-O-methyltransferase (COMT) by tolcapone, slowed down DA elimination in knockout mice. As DA half-life was two orders of magnitude higher in these mice, the DA diffusion distance was 10-times higher than in wild-types (100 and 10 microm, respectively). In knockout mice, alpha-methyl-p-tyrosine induced a much faster decline of DA release and haloperidol was less effective in potentiating DA release. Therefore, DA release was more dependent on DA synthesis than in normal animals but was less influenced by D2 autoregulation. Dopaminergic neurons exhibit two kinds of discharge activity, i.e. single spikes and bursts of 2-6 action potentials. In wild-type mice, stimuli mimicking bursts evoked significant increases in extracellular DA over its basal level sustained by tonic activity. However, in mice lacking the DAT, low frequency firing resulted in consistently high extracellular DA levels that could not be distinguished from DA levels achieved by high frequency firing. Therefore, the burst firing activity cannot be specifically translated into phasic changes in extracellular DA. This deficit might contribute to the difficulties of these mice in spatial cognitive function.

Animals↗

PubMed2000

Electrophysiological and behavioural evidence for an antagonistic modulatory role of adenosine A2A receptors in dopamine D2 receptor regulation in the rat dopamine-denervated striatum.

It has been shown that striatal adenosine A2A receptors can antagonistically interact with dopamine D2 receptors at the membrane level leading to a decrease in the affinity and efficacy of D2 receptors. Extracellular recordings and rotational behaviour were employed to obtain a correlate to these findings in an animal model of Parkinson's disease (PD). The recordings were performed in rats with unilateral 6-hydroxydopamine (6-OHDA)-induced catecholamine depletion. While recording in the dopamine-depleted striatum, local applications of the dopamine D2 agonist quinpirole reduced neuronal activity. However, when the adenosine A2A antagonist MSX-3 was applied simultaneously with quinpirole, the inhibition of neuronal firing seen after quinpirole alone was significantly potentiated (P< 0.001, n = 11). In contrast, local application of CGS 21680 attenuated the effect of quinpirole. The doses of MSX-3 and CGS 21680 used to achieve the modulation of quinpirole action had no effect per se on striatal neuronal firing. Furthermore, rotational behaviour revealed that MSX-3 dose-dependently increased the number of turns when administrated together with a threshold dose of quinpirole while no enhancement was achieved when MSX-3 was combined with SKF 38393. MSX-3 alone did not induce rotational behaviour. In conclusion, this study shows that low ineffective doses of MSX-3 enhance the effect of quinpirole on striatal firing rate, while the A2A agonist exerts the opposite action. This mechanism gives a therapeutic potential to A2A antagonists in the treatment of PD by enhancing D2 receptor function.

Adenosine↗

PubMed1981

Dopamine receptor binding in inbred mice: strain differences in mesolimbic and nigrostriatal dopamine binding sites.

Dopamine receptors were examined by Scatchard analysis in the striatal and olfactory tubercle regions of 11 inbred mouse strains. Simultaneous determinations of the binding characteristics of 3H-labeled 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN), a dopaminergic agonist, and [3H]spiroperidol, a dopaminergic antagonist, were examined. Among the 11 strains, the equilibrium dissociation constant (Kd) for agonist binding did not vary in either the striatum or the olfactory tubercle. Similarly, no strain differences were observed in the Kd for spiroperidol in either region, although the Kd for spiroperidol in the olfactory tubercle was uniformly higher than that in the striatum. Measurement of receptor concentrations revealed strain differences of up to 2-fold for both [3H]ADTN and [3H]spiroperidol binding sites. Within each brain region, the densities of agonist and antagonist binding sites correlated significantly. However, between brain regions there was no correlation in the density of agonist or antagonist binding sites, which suggests that mesolimbic and nigrostriatal dopamine neurons may be under independent genetic control. Analysis of [3H]spiroperidol displacement by clofluperol, aceperone, cinanserin, and mianserin in four inbred mouse strains revealed that 88-90% of the striatal spiroperidol sites are dopaminergic, with the remainder being serotonergic. In contrast, 53-66% of the olfactory tubercle [3H]spiroperidol binding sites are dopaminergic and 34-47% are serotonergic. These data suggest that genetic differences in serotonin receptors and dopamine receptors may exist among inbred mouse strains.

Animals↗