Control of the Subthalamic Innervation of Substantia Nigra Pars Reticulata by D1 and D2 Dopamine Receptors

2006 ◽  
Vol 95 (3) ◽  
pp. 1800-1811 ◽  
Author(s):  
Osvaldo Ibañez-Sandoval ◽  
Adán Hernández ◽  
Benjamin Florán ◽  
Elvira Galarraga ◽  
Dagoberto Tapia ◽  
...  
Keyword(s):  
Dopamine Receptors ◽  
Receptor Agonist ◽  
Sch 23390 ◽  
Receptor Activation ◽  
Skf 38393 ◽  
Projection Neurons ◽  
Patch Clamp Technique ◽  
D2 Dopamine Receptors ◽  
Endogenous Dopamine ◽  
Whole Cell Patch Clamp

The effects of activating dopaminergic D1 and D2 class receptors of the subthalamic projections that innervate the pars reticulata of the subtantia nigra (SNr) were explored in slices of the rat brain using the whole cell patch-clamp technique. Excitatory postsynaptic currents (EPSCs) that could be blocked by 6-cyano-7-nitroquinoxalene-2,3-dione and d-(−)-2-amino-5-phosphonopentanoic acid were evoked onto reticulata GABAergic projection neurons by local field stimulation inside the subthalamic nucleus in the presence of bicuculline. Bath application of ( RS)-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF-38393), a dopaminergic D1-class receptor agonist, increased evoked EPSCs by ∼30% whereas the D2-class receptor agonist, trans-(−)-4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo(3,4-g)quinoline (quinpirole), reduced EPSCs by ∼25%. These apparently opposing actions were blocked by the specific D1- and D2-class receptor antagonists: R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetra-hydro-1H-3-benzazepinehydrochloride (SCH 23390) and S-(−)-5-anino-sulfonyl- N-[(1-ethyl-2-pyrrolidinyl)-methyl]-2-methoxybenzamide (sulpiride), respectively. Both effects were accompanied by changes in the paired-pulse ratio, indicative of a presynaptic site of action. The presynaptic location of dopamine receptors at the subthalamonigral projections was confirmed by mean-variance analysis. The effects of both SKF-38393 and quinpirole could be observed on terminals contacting the same postsynaptic neuron. Sulpiride and SCH 23390 enhanced and reduced the evoked EPSC, respectively, suggesting a constitutive receptor activation probably arising from endogenous dopamine. These data suggest that dopamine presynaptically modulates the subthalamic projection that targets GABAergic neurons of the SNr. Implications of this modulation for basal ganglia function are discussed.

scholarly journals Localization and function of dopamine receptors in the subthalamic nucleus of normal and parkinsonian monkeys

2014 ◽  
Vol 112 (2) ◽  
pp. 467-479 ◽  
Author(s):  
Adriana Galvan ◽  
Xing Hu ◽  
Karen S. Rommelfanger ◽  
Jean-Francois Pare ◽  
Zafar U. Khan ◽  
...  
Keyword(s):  
Dopamine Receptors ◽  
Subthalamic Nucleus ◽  
Receptor Agonist ◽  
Rhesus Macaques ◽  
Extracellular Recording ◽  
Receptor Activation ◽  
D1 Receptors ◽  
Substantia Nigra Pars Compacta ◽  
D1 And D2 Receptors ◽  
And Function

The subthalamic nucleus (STN) receives a dopaminergic innervation from the substantia nigra pars compacta, but the role of this projection remains poorly understood, particularly in primates. To address this issue, we used immuno-electron microscopy to localize D1, D2, and D5 dopamine receptors in the STN of rhesus macaques and studied the electrophysiological effects of activating D1-like or D2-like receptors in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated parkinsonian monkeys. Labeling of D1 and D2 receptors was primarily found presynaptically, on preterminal axons and putative glutamatergic and GABAergic terminals, while D5 receptors were more significantly expressed postsynaptically, on dendritic shafts of STN neurons. The electrical spiking activity of STN neurons, recorded with standard extracellular recording methods, was studied before, during, and after intra-STN administration of the dopamine D1-like receptor agonist SKF82958, the D2-like receptor agonist quinpirole, or artificial cerebrospinal fluid (control injections). In normal animals, administration of SKF82958 significantly reduced the spontaneous firing but increased the rate of intraburst firing and the proportion of pause-burst sequences of firing. Quinpirole only increased the proportion of such pause-burst sequences in STN neurons of normal monkeys. In MPTP-treated monkeys, the D1-like receptor agonist also reduced the firing rate and increased the proportion of pause-burst sequences, while the D2-like receptor agonist did not change any of the chosen descriptors of the firing pattern of STN neurons. Our data suggest that dopamine receptor activation can directly modulate the electrical activity of STN neurons by pre- and postsynaptic mechanisms in both normal and parkinsonian states, predominantly via activation of D1 receptors.

Dopaminergic control of angiotensin II-induced vasopressin secretion in vitro

1998 ◽  
Vol 275 (4) ◽  
pp. E687-E693 ◽  
Author(s):  
Noreen F. Rossi
Keyword(s):  
Angiotensin Ii ◽  
Sch 23390 ◽  
Receptor Activation ◽  
Significant Rise ◽  
Skf 38393 ◽  
Receptor Subtype ◽  
Adrenergic Blockade ◽  
Adrenergic Antagonist ◽  
Vasopressin Secretion

Because dopamine influences arginine vasopressin (AVP) release, the present studies were designed to ascertain the dopamine receptor subtype that potentiates angiotensin II-induced AVP secretion in cultured hypothalamo-neurohypophysial explants. Dopamine (a nonselective D1/D2 agonist), apomorphine (a D2 ≫ D1 agonist), and SKF-38393 (a selective D1 agonist) dose dependently increased AVP secretion. Maximal AVP release was observed with 5 μM dopamine, 307 ± 66% ⋅ explant−1 ⋅ h−1, 1 μM SKF-38393, 369 ± 41% ⋅ explant−1 ⋅ h−1, and 0.1 μM apomorphine, 374 ± 67% ⋅ explant−1 ⋅ h−1. Selective D1 antagonism with 1 μM SCH-23390 blocked AVP secretion to values no different from basal. Domperidone (D2 antagonist), phenoxybenzamine (nonselective adrenergic antagonist), and prazosin (α1-antagonist) failed to prevent release. D1 antagonism also prevented AVP secretion to 1 μM angiotensin II [angiotensin II, 422 ± 87% ⋅ explant−1 ⋅ h−1vs. angiotensin II plus SCH-23390, 169 ± 28% ⋅ explant−1 ⋅ h−1( P < 0.05)], but D2 and α1-adrenergic blockade did not. In contrast, AT1 receptor inhibition with 0.5 μM losartan blocked angiotensin II- but not dopamine-induced AVP release. AT2antagonism had no effect. Although subthreshold doses of the agonists did not increase AVP secretion (0.05 μM dopamine, 133 ± 44% ⋅ explant−1 ⋅ h−1; 0.01 μM SKF-38393, 116 ± 26% ⋅ explant−1 ⋅ h−1;and 0.001 μM angiotensin II, 104 ± 29% ⋅ explant−1 ⋅ h−1), the combination of dopamine and angiotensin II provoked a significant rise in AVP [420 ± 83% ⋅ explant−1 ⋅ h−1( P < 0.01)]. Similar results were observed with SKF-38393 and angiotensin II, and the AVP response was blocked to basal levels by either D1 or AT1 antagonism. These findings support a role for D1 receptor activation to increase AVP release and mediate angiotensin II-induced AVP release within the hypothalamo-neurohypophysial system. The data also suggest that the combined subthreshold stimulation of receptors that use distinct intracellular pathways can prompt substantial AVP release.

Dopamine D-1/D-5 Receptor Activation Is Required for Long-Term Potentiation in the Rat Neostriatum In Vitro

2001 ◽  
Vol 85 (1) ◽  
pp. 117-124 ◽  
Author(s):  
J.N.D. Kerr ◽  
J. R. Wickens
Keyword(s):  
Receptor Antagonist ◽  
Learning And Memory ◽  
Sch 23390 ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Striatal Neurons ◽  
Theoretical Understanding ◽  
Endogenous Dopamine ◽  
Term Potentiation

Dopamine and glutamate are key neurotransmitters involved in learning and memory mechanisms of the brain. These two neurotransmitter systems converge on nerve cells in the neostriatum. Dopamine modulation of activity-dependent plasticity at glutamatergic corticostriatal synapses has been proposed as a cellular mechanism for learning in the neostriatum. The present research investigated the role of specific subtypes of dopamine receptors in long-term potentiation (LTP) in the corticostriatal pathway, using intracellular recording from striatal neurons in a corticostriatal slice preparation. In agreement with previous reports, LTP could be induced reliably under Mg2+-free conditions. This Mg2+-free LTP was blocked by dopamine depletion and by the dopamine D-1/D-5 receptor antagonist SCH 23390 but was not blocked by the dopamine D-2 receptor antagonist remoxipride or the GABAA antagonist picrotoxin. In dopamine-depleted slices, the ability to induce LTP could be restored by bath application of the dopamine D-1/D-5 receptor agonist, SKF 38393. These results show that activation of dopamine D-1/D-5 receptors by either endogenous dopamine or exogenous dopamine agonists is a requirement for the induction of LTP in the corticostriatal pathway. These findings have significance for current understanding of learning and memory mechanisms of the neostriatum and for theoretical understanding of the mechanism of action of drugs used in the treatment of psychotic illnesses and Parkinson's disease.

Effects of morphine withdrawal on catecholaminergic neurons on heart right ventricle; implication of dopamine receptors

2001 ◽  
Vol 79 (10) ◽  
pp. 885-891 ◽  
Author(s):  
M V Milanés ◽  
M T Marín ◽  
M L Laorden
Keyword(s):  
Right Ventricle ◽  
Receptor Antagonist ◽  
Dopamine Receptors ◽  
Biochemical Analysis ◽  
Sch 23390 ◽  
Receptor Activation ◽  
Morphine Withdrawal ◽  
Dopamine Turnover ◽  
Catecholaminergic Neurons ◽  
The Right

The purpose of our study was to examine the effects of D1-and D2-dopamine receptors blockade on the changes in the ventricular content of catecholamines in rats withdrawn from morphine. Rats were given morphine by subcutaneous (sc) implantation of morphine pellets for 5 days. On the eighth day, morphine withdrawal was induced by sc administration of naloxone (1 mg/kg), and rats were killed 30 min later. Pretreatment with SCH 23390 (dopamine D1, D5 receptor antagonist) 15 min prior to naloxone administration suppressed some the behavioural signs of morphine withdrawal, whereas eticlopride (dopamine D2, D3, D4 receptor antagonist) did not. In addition, biochemical analysis indicate that SCH 23390 completely abolished the withdrawal-induced increase in noradrenaline and dopamine turnover in the right ventricle. By contrast, eticlopride did not block the hyperactivity of catecholaminergic neurons in the heart during morphine withdrawal. These data suggest that the hyperactivity of catecholaminergic neurons in the heart during morphine withdrawal is dependent upon D1 dopamine receptor activation. In addition, our results exclude the involvement of D2 dopamine receptors.Key words: morphine withdrawal, right ventricle, catecholaminergic activity.

Dopamine DA1 receptor agonist, fenoldopam, reverses glycine-induced hyperfiltration in rats

1992 ◽  
Vol 262 (6) ◽  
pp. F1055-F1060 ◽  
Author(s):  
Y. X. Wang ◽  
M. Gellai ◽  
D. P. Brooks
Keyword(s):  
Glomerular Filtration Rate ◽  
Receptor Agonist ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Sch 23390 ◽  
Receptor Activation ◽  
Diabetic Rats ◽  
Glomerular Hyperfiltration ◽  
Filtration Fraction ◽  
Stimulation Of

Stimulation of dopamine DA1 receptors can prevent glomerular hyperfiltration in streptozotocin-induced diabetic rats. In the present study we have therefore investigated whether the DA1 agonist, fenoldopam, can prevent glycine-induced hyperfiltration. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and p-aminohippurate clearances in conscious chronically instrumented rats. Glycine (3.7 mg/min iv; n = 8) significantly increased GFR by 37% (from 1.09 +/- 0.53 to 1.49 +/- 0.11 ml.100 g-1.min-1, P less than 0.01), ERPF by 23% (from 2.96 +/- 0.30 to 3.64 +/- 0.43 ml.100 g-1.min-1, P less than 0.05), and filtration fraction (FF) by 13% (from 0.39 +/- 0.04 to 0.44 +/- 0.05, P less than 0.05). Fenoldopam, at a dose (1 microgram.kg-1.min-1 iv; n = 8) that increased ERPF by 26%, decreased FF by 13%, but did not change GFR, significantly attenuated the glycine-induced hyperfiltration. In the presence of fenoldopam, glycine resulted in only an 8% increase in GFR (from 1.08 +/- 0.07 to 1.17 +/- 0.09 ml.100 g-1.min-1; n = 8). ERPF increased by 20% (from 3.34 +/- 0.24 to 4.00 +/- 0.21 ml.100 g-1.min-1, P less than 0.05), and FF decreased by 13% (from 0.34 +/- 0.03 to 0.29 +/- 0.02, P less than 0.05). Infusion of the DA1-selective antagonist, Sch 23390, abolished the effects of fenoldopam. Thus DA1 receptor activation can prevent glomerular hyperfiltration induced by glycine.

Regulation of endogenous dopamine release in amphibian retina by gamma-aminobutyric acid and glycine

1994 ◽  
Vol 11 (5) ◽  
pp. 1003-1012 ◽  
Author(s):  
Jeffrey H. Boatright ◽  
Nara M. Rubim ◽  
P. Michael Iuvone
Keyword(s):  
Receptor Agonist ◽  
Dopamine Release ◽  
Receptor Activation ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Gaba A ◽  
Endogenous Dopamine ◽  
Endogenous Dopamine Release ◽  
Inhibitory Tone

AbstractEndogenous dopamine release in the retina of the African clawed frog (Xenopus laevis) increases in light and decreases in darkness. The roles of the inhibitory amino acid transmitters gamma-aminobutyric acid (GABA) and glycine in regulating this light/dark difference in dopamine release were explored in the present study. Exogenous GABA, the GABA-A receptor agonist muscimol, the GABA-B receptor agonist baclofen, and the GABA-C receptor agonist cis-aminocrotonic acid (CACA) suppressed light-evoked dopamine overflow from eyecups. The effects of GABA-A and -B receptor agonists were selectively reversed by their respective receptor-specific antagonists, whereas the effect of CACA was reversed by the competitive GABA-A receptor antagonist bicuculline. The benzodiazepine diazepam enhanced the effect of muscimol on light-evoked dopamine release. Both GABA-A and -B receptor antagonists stimulated dopamine release in light or darkness. Bicuculline was more potent in light than in darkness. These data suggest that retinal dopaminergic neurons are inhibited by GABA-A and -B receptor activation in both light and darkness but that GABA-mediated inhibitory tone may be greater in darkness than in light.Exogenous glycine inhibited light-stimulated dopamine release in a concentration-dependent and strychnine-sensitive manner. However, strychnine alone did not increase dopamine release in light or darkness, nor did it augment bicuculline-stimulated release in darkness. Additionally, both strychnine and 7-chlorokynurenate, an antagonist of the strychnine-insensitive glycine-binding site of the N-methyl-D-aspartate subtype of glutamate receptor, suppressed light-evoked dopamine release. Thus, the role of endogenous glycine in the regulation of dopamine release remains unclear.

Dopamine D1 receptor analogues act centrally to stimulate prolactin secretion in ewes

1993 ◽  
Vol 137 (3) ◽  
pp. 457-464 ◽  
Author(s):  
J. D. Curlewis ◽  
I. J. Clarke ◽  
A. S. McNeilly
Keyword(s):  
Receptor Agonist ◽  
Sch 23390 ◽  
Prolactin Secretion ◽  
D1 Receptor ◽  
Skf 38393 ◽  
Plasma Prolactin ◽  
Intravenous Injections ◽  
Inhibiting Factors ◽  
Prolactin Response ◽  
The Brain

ABSTRACT It is well known that prolactin secretion is inhibited by dopamine acting via the pituitary dopamine D2 receptor. Dopamine D1 receptor analogues also affect prolactin levels although the mechanisms and physiological significance are poorly understood. The present study of the ewe was undertaken to characterize the effects of the D1 receptor agonist SKF 38393 and antagonist SCH 23390 on prolactin in this species and to determine whether the prolactin response to both drugs requires an intact hypothalamo-pituitary axis. Ovariectomized ewes were injected intravenously with vehicle, 0·2, 2 or 20 mg SKF 38393 (D1 agonist) or SCH 23390 (D1 antagonist). At the 20 mg dose, plasma prolactin concentrations were significantly (P <0·01) increased by each drug and returned within an hour to control levels. When injected directly into the lateral ventricles of the brain (intracerebroventricular (i.c.v.) injection), a 100-fold lower dose of SKF 38393 (0·2 mg; P <0·05) was sufficient to stimulate prolactin secretion. In contrast, i.c.v injection of SCH 23390 (0·02 and 0·2 mg) had no effect on prolactin levels and at no dose was there evidence for suppression of prolactin levels. These results are in accord with earlier studies in the rat which suggested that the D1 agonist stimulated prolactin secretion via a direct effect on central dopamine D1 receptors whereas the D1 antagonist interacted with the pituitary dopamine D2 receptor to increase prolactin secretion. In a further experiment this hypothesis was tested in hypothalamo-pituitary disconnected ewes which were infused with dopamine (0·5 μg/kg per min) for 3 h. After 2 h of the dopamine infusion, animals were challenged with intravenous injections of the vehicle, 20 mg SKF 38393, 20 mg SCH 23390 or 2 mg domperidone (dopamine D2 antagonist). Infusion of dopamine was followed by a significant (P <0·05) decline in prolactin concentrations so that after 2 h prolactin levels were 40% of the preinfusion value. Following injection of the vehicle, SCH 23390 or SKF 38393, prolactin levels continued to decline for the remainder of the experiment. As expected, injection of domperidone was followed by a significant (P <0·05) increase in prolactin to reach peak levels after 30 min. These results demonstrate that peripheral injections of the dopamine D1 agonist SKF 38393 or antagonist SCH 23390 increase prolactin secretion in the ewe. The prolactin response to either drug requires an intact hypothalamo-pituitary axis indicating that SKF 38393 and SCH 23390 act at some central site(s) which is linked with hypothalamic secretion of prolactin-releasing or -inhibiting factors. Journal of Endocrinology (1993) 137, 457–464

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