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At least 343 records · Page 19Linked to original sources
PubMed1999

Inverse agonist properties of dopaminergic antagonists at the D(1A) dopamine receptor: uncoupling of the D(1A) dopamine receptor from G(s) protein.

The interaction of dopaminergic antagonists with the D(1A) dopamine receptor was assessed in PC2 cells that transiently express this receptor. The maximal binding and dissociation constants for the D(1A) dopamine receptor, using the ligand [(125)I]SCH23982 were 0.38 +/- 0.09 nM and 1 to 4 pmol/mg, respectively, when assessed 48 h after transfection with cDNA encoding the rat D(1A) receptor. Basal adenylyl cyclase activity increased 50 to 60% in membranes of transfected PC2 cells compared with control membranes. The dopaminergic antagonists clozapine, cis-flupenthixol, (+)-butaclamol, haloperidol, chlorpromazine, and fluphenazine inhibited constitutive adenylyl cyclase activity in membranes of cells expressing the D(1A) receptor. SCH23390, a selective D(1) dopamine receptor antagonist, and (-)-butaclamol did not alter basal cyclase activity, whereas dopamine increased enzyme activity in membranes expressing the D(1A) dopamine receptor. The coupling of D(1A) receptors with G(s) proteins was examined by immunoprecipitation of membrane G(salpha) followed by immunoblotting with a D(1A) dopamine receptor monoclonal antibody. Clozapine, cis-flupenthixol, (+)-butaclamol, haloperidol, and fluphenazine but not SCH23390 or (-)-butaclamol decreased D(1A) receptor-G(salpha) coupling by 70 to 80%, and SCH23390 was able to prevent the receptor-G(salpha) uncoupling induced by haloperidol or clozapine. These results indicate that some dopaminergic antagonists suppress basal signal transduction and behave as inverse agonists at the D(1A) dopamine receptor. This action of the dopamine receptor antagonists may contribute to their antidopaminergic properties that seem to underlie their clinical actions as antipsychotic drugs.

Adenylyl Cyclases↗
PubMed2005

Dopamine, dopamine D2 receptor short isoform, transforming growth factor (TGF)-beta1, and TGF-beta type II receptor interact to inhibit the growth of pituitary lactotropes.

The neurotransmitter dopamine is known to inhibit prolactin secretion and the proliferation of lactotropes in the pituitary gland. In this study, we determined whether dopamine and TGFbeta1 interact to regulate lactotropic cell proliferation. We found that dopamine and the dopamine agonist bromocriptine stimulated TGFbeta1 secretion and TGFbeta1 mRNA expression but inhibited lactotropic cell proliferation both in vivo and in vitro. The dopamine's inhibitory action on lactotropic cell proliferation was blocked by a TGFbeta1-neutralizing antibody. We also found that PR1 cells, which express low amounts of the dopamine D2 receptor, demonstrated reduced expression of TGFbeta1 type II receptor and TGFbeta1 mRNA levels and had undetectable levels of TGFbeta1 protein. These cells showed a reduced TGFbeta1 growth-inhibitory response. Constitutive expression of the D2 receptor short isoform, but not the D2 receptor long isoform, induced TGFbeta1 and TGFbeta1 type II receptor gene expression and recovered dopamine- and TGFbeta1-induced growth inhibition in PR1 cells. The constitutive expression of D2 receptor short isoform also reduced the tumor cell growth rate. These data suggest that a TGFbeta1 system may mediate, in part, the growth-inhibitory action of dopamine on lactotropes.

Activin Receptors, Type I↗
PubMed1984

Prolactin secretion from human prolactinomas perifused in vitro: effect of TRH, prostaglandin E1, theophylline, dopamine and dopamine receptor blockers.

To clarify the functional characteristics of prolactin (Prl)-producing adenoma cells, the effect of TRH, prostaglandin E1 (PGE1), theophylline, dopamine and dopaminergic antagonists on Prl secretion was examined in vitro in perifused pituitary adenoma tissues obtained at surgery from 8 patients with prolactinoma. Perifusion with TRH at a concentration of 10(-6) to 10(-5) M resulted in a significant increase in effluent Prl levels in 3 of the 8 adenoma tissues. In the remaining 5 adenomas, TRH produced no effect on Prl release in vitro. On the other hand, PGE1 (10(-5) M) stimulated Prl secretion in 2 of the 4 adenomas examined. Addition of theophylline (5.5 mM) caused a marked increase of effluent Prl levels in all 8 prolactinomas regardless of the reactivity to TRH or PGE1. Dopamine (5 X 10(-7) M) suppressed Prl secretion from adenoma tissue in 5 of 7 patients tested but had no effect in the remaining two adenomas. When perifused simultaneously with dopamine, sulpiride (D2-selective dopamine receptor blocker, 5 X 10(-7) M) blocked the inhibitory effect of dopamine on Prl release in 3 of the 4 dopamine-sensitive prolactinomas. In one adenoma responsive to dopamine but resistant to sulpiride, YM-09151-2 (relatively specific D1-dopamine receptor blocker, 5 X 10(-7) M) antagonized the dopaminergic inhibition of Prl release. When perifused alone, neither sulpiride nor YM-09151-2 affected Prl release from any of the adenoma tissues tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Effects of dopamine and dopamine antagonists on postprandial release of pancreatic polypeptide in dogs and in healthy volunteers.

The effect of dopamine, 0.006, 0.12, 1.2, and 2.4 mg X kg-1 X h1, and the dopamine antagonist sulpiride on postprandial pancreatic polypeptide (PP) release has been studied in dogs. Dopamine reduced PP release, the reduction ranging between 28% and 97% of the integrated PP response after food. The inhibition obtained with dopamine, 0.12 and 2.4 mg X kg-1 X h-1, could be partly reversed (p less than 0.05) by sulpiride, 7.5 mg X kg-1. The concomitant administration of phentolamine, 1.0 mg X kg-1, and propranolol, 0.5 mg X kg -1, partly reversed the inhibition obtained with dopamine, 2.4 mg X kg-1 X h-1 (p less than 0.05). In healthy volunteers basal PP concentration and postprandial PP release were diminished by dopamine, 0.12 mg X kg-1 X h-1 (p less than 0.02). Sulpiride in dogs and haloperidol in volunteers reduced PP release when given without concomitant administration of dopamine. It is concluded that dopamine inhibits postprandial PP release via both dopaminergic and adrenergic receptors.

Adrenergic beta-Antagonists↗
PubMed1999

Dopamine induces neutrophil apoptosis through a dopamine D-1 receptor-independent mechanism.

BACKGROUND: For the normal resolution of an acute inflammatory response, neutrophil (PMN) apoptosis is essential to maintain immune homeostasis and to limit inappropriate host tissue damage. A delay in PMN apoptosis has been implicated in the pathogenesis of the systemic inflammatory response syndrome (SIRS). Dopamine, a biogenic amine with known cardiovascular and neurotransmitter properties, is used in patients with SIRS to maintain hemodynamic stability. We sought to determine whether dopamine may also have immunoregulatory properties capable of influencing PMN apoptosis, function, and activation state in patients with SIRS. METHODS: PMNs were isolated from healthy volunteers and patients with SIRS and treated with varying doses of dopamine and a dopamine D-1 receptor agonist, fenoldopam. PMN apoptosis was assessed every 6 hours with use of propidium iodide DNA staining and PMN function was assessed with use of respiratory burst activity, phagocytosis ability, and CD11a, CD11b, and CD18 receptor expression as functional markers. RESULTS: There was a significant delay in PMN apotosis in patients with SIRS compared with controls. Treatment of isolated PMNs from both healthy controls and patients with SIRS with 10 and 100 mumol/L dopamine induced apoptosis. PMN ingestive and cytocidal capacity were both decreased in patients with SIRS compared with controls. Treatment with dopamine significantly increased phagocytic function. Fenoldopam did not induce PMN apoptosis. CONCLUSION: Our data demonstrate for the first time that dopamine induces PMN apoptosis and modulates PMN function both in healthy controls and in patients with SIRS. These results indicate that dopamine may be beneficial during SIRS through a nonhemodynamic PMN-dependent proapoptotic mechanism.

Adult↗
PubMed1995

Mechanism of the dopamine-releasing actions of amphetamine and cocaine: plasmalemmal dopamine transporter versus vesicular monoamine transporter.

The effects of amphetamine and cocaine were studied in [3H]-dopamine-loaded and superfused COS-7 cells transfected with either the cDNA of the plasmalemmal dopamine transporter ("DAT cells") or the cDNA of the vesicular amine transporter ("VAT cells"), or with both transporters ("DAT/VAT cells"). Amphetamine (0.01-100 microM, added for 4 min of superfusion) led to a concentration-dependent increase in dopamine release in DAT cells, as well as in DAT/VAT cells. The EC50 of the effect of amphetamine on DAT cells was 1.1 +/- 0.6 microM; the effect on DAT/VAT cells did not reach a plateau in the concentration range tested. With longer exposure to amphetamine, dopamine efflux from DAT cells reached a peak and quickly returned to baseline, in spite of the continued presence of the drug, whereas in DAT/VAT cells and in VAT cells the effect was sustained. Cocaine (up to 100 microM) did not exert any effect of its own in DAT cells or VAT cells but inhibited the amphetamine-induced release of dopamine from DAT cells in a competitive manner. In DAT/VAT cells cocaine and its analogue (-)-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane caused an efflux of dopamine resembling that caused by amphetamine but quantitatively much smaller. The rank order of potency was the same as in uptake experiments [(-)-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane > cocaine]. The effect of cocaine was mimicked by the reduction of chloride. The results indicate that there is a plasmalemmal component and a vesicular component in the dopamine-releasing action of amphetamine. The releasing action of cocaine is dependent on the existence of a vesicular pool of the neurotransmitter and seems to be linked to inhibition of the plasmalemmal dopamine transporter.

Amphetamine↗
PubMed2000

Sensitivity of binding of high-affinity dopamine receptor radioligands to increased synaptic dopamine.

PET and SPECT studies have documented that D2 radioligands of moderate affinity, but not radioligands of high affinity, are sensitive to pharmacological challenges that alter synaptic dopamine levels. The objective of this work was to determine whether the brain kinetics of high-affinity radioligands for dopamine D1 ([(3)H]SCH 23390) and D2 ([(123)I]epidepride) receptors were altered by a prolonged elevation of synaptic dopamine induced by the potent cocaine analog RTI-55. Mice were injected intravenously with radioligands either 30 min after or 4 h before intraperitoneal administration of RTI-55 (2 mg/kg). In separate experiments, the pharmacological effects of RTI-55 were assessed biochemically by measuring uptake of dopamine in synaptosomes prepared from RTI-treated mice and behaviorally by monitoring locomotor activity. Consistent with the expected elevation of synaptic dopamine, RTI-55 induced a long-lasting decrement in dopamine uptake measured ex vivo, and a prolonged increase in locomotor activity. RTI-55 injected prior to the radioligands induced a significant (P < 0.05) increase in striatal concentration of [(123)I]epidepride at 15 min, relative to saline-treated controls, but there were no differences between the two groups at later time-points. For [(3)H]SCH 23390, both initial striatal uptake and subsequent clearance were slightly increased by preadministration of RTI-55. Administration of RTI-55 4 h after the radioligands (i.e., when it was presumed that a state of near equilibrium binding of the radioligands had been reached), was associated with a significant reduction of striatal radioactivity for both radiotracers. Our results are consistent with increased competition between dopamine and radioligand for binding to both D1 and D2 receptors after treatment with RTI-55. We suggest that the magnitude of the competition is reduced by failure of the receptor binding of high-affinity radioligands to rapidly attain equilibrium.

Animals↗
PubMed2001

Atypical kinetics for a series of putative dopamine antagonists to reverse the low-magnitude Ca2+ phase in the dopamine-bound D2short receptor state.

Real-time analysis of dopamine:antagonist interactions at the recombinant D2short receptor was performed by measuring time-dependent Ca2+ responses following activation of a chimeric Galphaq/o protein in CHO-K1 cells. Terguride (57%), +-UH 232 (20%) and buspirone (16%) demonstrated dopamine-like intrinsic activity at the presumably unoccupied, dopamine-free receptor; remoxipride, pipamperone and L 741626 being silent at 1 microM. Each of the putative antagonists (1 microM) displayed a transient reversal capacity of the low-magnitude Ca2+ phase in the dopamine-bound receptor state ( E(rev): 68%-92% vs. 1 microM tropapride) with a t1/2 between 8.8 s and 13.9 s upon antagonist addition; this capacity was either almost fully [remoxipride, pipamperone and +-UH 232] or partially [buspirone (31%), terguride (45%) and L 741626 (70%)] lost upon further incubation. The biphasic reversal Ca2+ profile of these dopamine antagonists is different from previously characterised dopamine antagonists which display either full reversal of the low-magnitude Ca2+ response with a fast or slow onset of action, or partial reversal stably present over the entire incubation period. The dynamic Ca2+ data strongly suggest that the dopamine D2short receptor can be blocked via multiple molecular mechanisms.

Animals↗
PubMed2006

L-DOPA inhibits depolarization-induced [3H]GABA release in the dopamine-denervated globus pallidus of the rat: the effect is dopamine independent and mediated by D2-like receptors.

The effect of L-DOPA on [(3)H]GABA release in slices of globus pallidus from 6-OHDA-lesioned rats was studied. Release was evoked by high (15 mM) K(+). The lesion reduced dopamine content and dopamine synthesized from L-DOPA. The inhibition of DOPA decarboxylase blocked dopamine synthesis. Endogenous dopamine released by high K(+) inhibited [(3)H]GABA release in normal but not in lesioned slices. L-DOPA inhibited (IC(50) = 0.44 microM) evoked [(3)H]GABA release. The inhibition was via D2-like receptors but not mediated by dopamine. The turning behavior induced by L-DOPA methyl ester (25 mg/kg, i.p.) was not abolished by the DOPA decarboxylase inhibitor 3-hydroxybenzylhydrazine but in this condition it was abolished by sulpiride. Results suggest that L-DOPA acting as D2-like agonist inhibits GABA release in the rat globus pallidus and induces turning behavior in rats with unilateral lesions of the dopamine innervation. L-DOPA could control Parkinson's disease symptoms acting not only as dopamine precursor but also by itself.

Animals↗
PubMed1996

Rats bred for enhanced apomorphine susceptibility have elevated tyrosine hydroxylase mRNA and dopamine D2-receptor binding sites in nigrostriatal and tuberoinfundibular dopamine systems.

From a Wistar population two rat lines were generated using as criterion the behavioral response to the dopamine agonist apomorphine. Rats of the apomorphine-susceptible (apo-sus) line revealed a vigorous gnawing response to apomorphine administration while the other rat line, the apomorphine-unsusceptible (apo-unsus) line, was selected for lack of response to the drug. In the present study using the 12th and 13th generation of these genetically selected lines, we have investigated whether this difference in apomorphine responsiveness was correlated with changes in dopamine neurochemistry. Therefore, we measured tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine synthesis, as well as dopamine D1 and D2 receptor mRNA levels in discrete brain regions by in situ hybridization. Dopamine (D2/D3) receptor binding was assessed with [125I]iodosulpride in a membrane binding assay and by quantitative autoradiography on tissue sections. [3H]SCH 23390 was used to analyze D1 receptor binding. Apo-sus rats displayed significantly higher TH mRNA levels in the A9 cell group of the substantia nigra pars compacta and in the A12 cell group of the arcuate nucleus. No difference was found in the A10 cell group of the VTA and the A6 cell group of the locus coeruleus. The density of D2/3 binding sites as well as D1 receptor mRNA levels in the striatal projection area of the A9 substantia nigra neurons, were significantly elevated in apo-sus rats. Dopamine D2 receptor mRNA and D1 receptor binding levels in caudate putamen and nucleus accumbens, however, were similar in rats of both lines. In conclusion, high apomorphine susceptibility is related to a potentially enhanced dopamine responsiveness selective for the nigrostriatal and tuberoinfundibular pathways.

Animals↗
PubMedDate not supplied

Dopamine re-uptake inhibitor GBR-12909 induction of aberrant behaviors in animal models of dopamine dysfunction.

Many individuals with mental retardation exhibit chronic aberrant behaviors (CABs) that includes hyperactive, stereotyped, aggressive, and self-injurious behaviors. Brain imaging studies have found that several of these individuals have abnormalities in their dopaminergic neurotransmitter systems that are thought to be responsible in part, for the development of these behaviors. The present study evaluated the effects of a selective dopamine re-uptake blocker, GBR-12909 in three animal models of varying striatal dopamine concentrations. The three animal models included the neonatal 6-hydroxydopamine (6-OHDA)-lesioned rat, a model of dopamine neuronal depletion, the prenatal methylazoxymethanol (MAM)-exposed rat, a model of hyper-dopaminergic innervation and control rats, a model of normal dopaminergic function. The animals were given five daily injections of GBR-12909 and videotaped observations were conducted immediately following the injections and 6h later. The results of the study indicate that the MAM-treated rats exhibited more hyperactive behaviors than either the 6-OHDA or the control animals in response to the GBR-12909 injections. However, the 6-OHDA and control rats exhibited more self-injurious behaviors than the MAM rats. Interestingly, the topography of the self-injurious behavior exhibited differed from that we have previously observed in 6-OHDA lesioned rats following dopamine agonists and resembles the mouthing behaviors seen in some individuals with mental retardation, in particular those with Rett syndrome. These findings indicate the models of varying dopaminergic function interact differently with a dopamine re-uptake blocker than dopamine agonists and that the partially dopamine depleted model may model the behaviors seen in individuals with Rett syndrome.

Animals↗
PubMed2002

A possible substrate for dopamine-related changes in mood and behavior: prefrontal and limbic effects of a D3-preferring dopamine agonist.

Dopamine can induce fascinating, complex human behavioral states, including disinhibition, euphoria, or elaborate stereotypies, whereas dopamine deficiency can cause anxiety or sadness. Limited data suggest that these phenomena may involve dysfunction of orbital frontal cortex, cingulate cortex, or ventral striatum. The dopamine D3 receptor (D3R) has an anatomic distribution that suggests it could mediate these effects, but almost no data directly demonstrate the regional functional effects of D3R activation. We used quantitative positron emission tomography (PET), [15O]water, and the D3-preferring dopamine agonist pramipexole to identify D3-mediated regional cerebral blood flow (rCBF) responses in living primates. We studied seven normal baboons ventilated with 70% nitrous oxide, and analyzed results voxelwise in a common atlas space. At clinically relevant doses, pramipexole produced statistically robust decreases in rCBF in bilateral orbitofrontal cortex, thalamus, operculum, posterior and anterior (subgenual) cingulate cortex, and insula (in decreasing order of significance). Cortical areas related to movement were relatively unaffected, and rCBF did not change in cerebellum or visual cortex. The dose-response curve and duration of pramipexole's effects suggest that these rCBF responses indicate functional effects of a D3-preferring agonist. A D2-preferring agonist studied under the same conditions produced a quantitatively different pattern of responses. We conclude that a dopamine D3 receptor agonist preferentially affects brain activity in prefrontal and limbic cortex, and speculate that dopamine's effects on these regions via D3Rs may mediate some of the known psychiatric complications of dopamine deficiency or excess.

Animals↗
PubMed1996

Inhibition of dopamine synthesis by dopamine D2 and D3 but not D4 receptors.

The goal of the current study was to determine which of the D2-like receptors (D2, D3 or D4) are involved in autoreceptor regulation of dopamine synthesis. We have derived a model system utilizing a mouse mesencephalic cell line, MN9D, which both synthesizes and releases dopamine, to characterize the modulation of tyrosine hydroxylase activity, the rate limiting enzyme in the conversion of tyrosine to dopamine, by the D2-like receptors. Previously, we have shown that stimulation of D2 and D3, but not D4, dopamine receptors transfected into MN9D cells inhibited the release of dopamine. In the current study, we show that quinpirole stimulation of transfected D2 and D3, but not D4, dopamine receptors inhibited K+-stimulated tyrosine hydroxylase activity in a pertussis toxin-sensitive manner, strongly suggesting G-protein coupling as a mechanistic pathway. The D2 receptor effect could be maintained for at least 60 min, whereas the D3 receptor effect desensitized. Treatment with 10 microM forskolin, which raises cyclic AMP levels or with 100 nM okadaic acid, a potent phosphatase inhibitor, had no effect on the D2-or D3-mediated inhibition, suggesting that these effects may be independent of both cyclic AMP- and okadaic acid-sensitive phosphatase activity. Taken together, these data confirm the hypothesis that dopamine D2 and D3 receptors can perform dual roles in autoreceptor regulation.

Animals↗
PubMed1998

Internalization of D1 dopamine receptor in striatal neurons in vivo as evidence of activation by dopamine agonists.

To investigate how dopamine influences the subcellular localization of the dopamine receptors in the striatal dopaminoceptive neurons, we have used immunohistochemistry to detect D1 dopamine receptors (D1R) after modifications of the dopamine environment. In normal rats, D1R are located mostly extrasynaptically at the plasma membrane of the cell bodies, dendrites, and spines. The intrastriatal injection of the full D1R agonist SKF-82958 and the intraperitoneal injection of the same molecule or of amphetamine (which induces a massive release of dopamine in the striatum) induce modifications of the pattern of D1R immunoreactivity in the dorsal and ventral striatum. Whereas normal rats display homogenous staining of the neuropile with staining of the plasma membrane of the cell bodies, either treatment provokes the appearance of an intense immunoreactivity in the cytoplasm and the proximal dendrites. The labeling pattern is heterogeneous and more intense in the striosomes than in the matrix. Analysis of semithin sections and electron microscopy studies demonstrates a translocation of the labeling from the plasma membrane to endocytic vesicles and endosomes bearing D1R immunoreactivity in the cytoplasm of cell bodies and dendrites. Injection of D1R antagonist (SCH-23390) alone or injection of D1R antagonist, together with amphetamine or SKF-82958, do not provoke modification of the immunoreactivity, as compared with normal rat. Our results demonstrate that, in vivo, the acute activation of dopamine receptors by direct agonists or endogenously released dopamine provokes dramatic modifications of their subcellular distribution in neurons, including internalization in the endosomal compartment in the cytoplasm. This suggests that modifications of the localization of neurotransmitter receptors, including extrasynaptic ones, may be a critical event that contributes to the postsynaptic response in vivo.

Animals↗
PubMed1996

Initial increases in extracellular dopamine in the ventral tegmental area provide a mechanism for the development of desipramine-induced sensitization within the midbrain dopamine system.

In an attempt to understand the basis of the changes in the mesolimbic dopamine system that occur in response to chronic treatment with the antidepressant drug, desipramine HCl (DMI), we monitored changes in extracellular dopamine in ventral tegmental area (VTA) and nucleus accumbens septi (NAS) using in vivo microdialysis in freely moving animals. Early in treatment at a time before changes in the responsiveness of the dopamine system are observed, basal levels of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were found to be increased in the VTA of rats treated with 5.0 mg/kg DMI twice daily for 6 days compared to those of saline-treated animals. After 12 days of treatment, and in a second group of animals after 18 days of treatment, basal levels of dopamine, DOPAC, HVA and 5HIAA, and levels in response to challenge with 1.5 mg/kg d-amphetamine sulphate were measured in the NAS. No differences in these measures taken in NAS were found between DMI- and saline-pretreated animals after 12 days of treatment. In DMI-treated animals tested after 18 days, the dopamine response to amphetamine was elevated compared to that of saline-treated animals. Furthermore, although there were no differences in basal levels of dopamine, basal levels of DOPAC and HVA were increased in DMI-treated animals. These findings lend support to the view that the time-dependent sensitization of dopaminergic function brought about by the tricyclic antidepressants may share processes in common with the development of sensitization to the indirect dopamine receptor agonist, amphetamine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Dopamine and non-dopamine psychoses.

The time course of antipsychotic response following the initiation of an antipsychotic drug and functional dopamine receptor sensitivity were explored in a cohort of recently admitted psychotic (mood-incongruent) patients. The distribution of the latencies of antipsychotic response suggested at least two populations. Rapid responders (RRs) had 60% reduction of baseline psychotic symptoms by a mean of 5.5 days of drug treatment. Delayed/nonresponders required 2-7 weeks for a similar reduction of psychotic symptoms. The sensitivity of postsynaptic dopamine receptors was explored using a neuroendocrine probe: growth hormone response to the dopamine agonist, apomorphine (AP). RRs had an exaggerated growth hormone response to AP in comparison to delayed/nonresponders (P less than 0.05). Exaggerated sensitivity of postsynaptic dopamine receptors and rapid antipsychotic response following dopamine receptor blockade in RRs suggest a true functional dopamine hypersensitivity disorder in the RR group. In contrast, lower postsynaptic receptor sensitivity (as reflected by lower growth hormone response to AP) and failure of early response following dopamine receptor blockade focus attention away from dopamine hyperactivity as a relevant etiologic mechanism in delayed/nonresponders. Response rates to neuroleptic drugs and neuroendocrine probes of receptor sensitivity may separate two or more etiologically distinct diseases with schizophrenic-like symptoms.

Antipsychotic Agents↗
PubMed1985

Effects of 6-hydroxydopamine on dopamine and noradrenaline content in dog blood vessels and heart. Evidence for a noradrenaline-independent dopamine pool.

The noradrenaline and dopamine depletion induced by 6-hydroxydopamine (6-OHDA) and pargyline plus 6-OHDA was investigated in the heart, mesenteric, renal, splenic and femoral arteries and saphenous vein of the dog. Catecholamine concentrations in plasma were also analyzed in these two experimental conditions. 6-OHDA and pargyline plus 6-OHDA induced a parallel decrease of the noradrenaline and dopamine content in the main trunk of the mesenteric artery, femoral artery and heart. In the proximal branches of the mesenteric artery, renal and splenic arteries 6-OHDA selectively reduced noradrenaline (by 50%) without changes in dopamine levels. Previous treatment with pargyline abolished this selectivity and depleted the tissue levels of both noradrenaline and dopamine by 75%. The noradrenaline and dopamine levels in the saphenous vein were not significantly reduced by 6-OHDA (15%) and pargyline plus 6-OHDA (40%). 6-OHDA and pargyline plus 6-OHDA increased both noradrenaline and adrenaline concentrations in plasma, without significant changes in dopamine concentrations. The present findings suggest: an independent dopamine presence in the proximal branches of the mesenteric artery, renal artery and splenic artery; that noradrenaline and dopamine are in one and the same structure in the heart, femoral artery and the main trunk of the mesenteric artery; the saphenous vein is more resistant to chemical sympathectomy than arterial blood vessels; the changes in plasma catecholamine concentrations are probably related to a compensatory mechanism initiated at the adrenal medulla.

Animals↗
PubMed2004

Glutamate-dopamine in vivo interaction in the prefrontal cortex modulates the release of dopamine and acetylcholine in the nucleus accumbens of the awake rat.

In the context of the in vivo neurochemical literature this article reviews some recent microdialysis studies in our laboratory of glutamate-dopamine interaction in the prefrontal cortex (PFC) and its possible role in modulating dopamine and acetylcholine release in the nucleus accumbens. A functional glutamate-dopamine interaction in PFC has been reported by microdialysis studies showing that both stimulation and blockade of prefrontal glutamate receptors produce changes of basal and/or stimulated release of dopamine in this area of the brain. These studies suggest that dopamine function in PFC is modulated locally by prefrontal glutamatergic inputs and that glutamate and dopamine can act simultaneously to regulate GABA release in PFC. In particular, dopamine can enhance the increases of extracellular GABA produced by the stimulation of prefrontal glutamate receptors. We report also that the stimulation of prefrontal D2 and mGluI receptors and their interaction changes the release of dopamine and acetylcholine in the nucleus accumbens.

Acetylcholine↗