Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of neurones in the substantial nigra and ventral tegmentum was recorded extracellularly in vitro. Dopamine produced depression of spontaneous firing in a dose-dependent manner. Antagonism of these neuronal responses to dopamine by metoclopramide, SCH 23390 and clozapine was examined. Metoclopramide antagonised the responses to dopamine in the manner expected; SCH 23390 had little effect on the response to dopamine as would be predicted for a selective dopamine "D1" antagonist. Clozapine did not produce the expected antagonism of the response to dopamine. The results at the single neurone level are compared with behavioural and biochemical data.
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PMID:Sensitivity of neuronal dopamine response in the substantia nigra and ventral tegmentum to clozapine, metoclopramide and SCH 23390. 329 79

The effects of both activation and blockade of dopamine (DA) D1 receptors on long-term depression (LTD) of synaptic transmission were examined in CA1 neurons of rat hippocampal slices. Low frequency stimulation (LFS) consisting of 450 pulses at 1 Hz induced LTD (-14.3%, mean, n = 10) in the slope of the field excitatory postsynaptic potential. SKF-38393 (3-10 microM), an agonist of DA D1 receptors, significantly enhanced LFS-induced LTD (-31.1%, n = 11). SCH-23390 (2 microM), an antagonist of DA D1 receptors, blocked the induction of LTD by LFS (2.5%, n = 6). These results indicate that DA D1 receptors play an important role in the modulation of LFS-induced LTD in rat hippocampal CA1 neurons.
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PMID:Activation of dopamine D1 receptors enhances long-term depression of synaptic transmission induced by low frequency stimulation in rat hippocampal CA1 neurons. 760 7

Selective CCKA and CCKB receptor agonists and antagonists were used to study the involvement of endogenous cholecystokinin in the behavioural changes that occur in mice in the forced-swimming test (Porsolt's test). The CCKB receptor antagonist, L-365,260 ((3R)-(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl)-3-methylphenylurea), but not the CCKA receptor antagonist, devazepide ((3S)-(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin -3-yl)- 1H-indole-2-carboxamide), elicited an antidepressant-type response (a decrease in the duration of immobility) that was suppressed by previous treatment with either CCK-8 (H-Asp-Tyr(OSO3H)-Met-Gly- Trp-Met-Asp-Phe-NH2) or the selective CCKB receptor agonist BC-264 (Boc-Tyr(SO3H)-gNle-mGly-Trp-N(Me)-Nle-Asp-Phe- NH2). The L-365,260 effect was also prevented by the dopamine receptor antagonist, SCH-23,390 (a dopamine D1-selective receptor antagonist: R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl- 2,3,4,5-tetrahydro-1H-3-benzazepine) and sulpiride (a dopamine D2-selective receptor antagonist: (-)-5-(aminosulfonyl)-N-[(1-ethyl-2-pyrrolidinyl) methyl]-2-metoxybenzamide). On the other hand, co-administration of subthreshold doses of L-365,260 and nomifensine (an atypical antidepressant that selectively blocks dopamine re-uptake mechanisms, 1,2,3,4-tetrahydro-2-methyl-4-phenyl-8-isoquinolinamine) led to a potent antidepressant-type response. These results indicate that blocking of CCKB receptors could result in an increase of extracellular dopamine contents in some brain areas involved in depression and suggest a potential use of CCKB receptor antagonists, alone or combined with antidepressants, in the treatment of depressive syndromes.
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PMID:The CCKB receptor antagonist, L-365,260, elicits antidepressant-type effects in the forced-swim test in mice. 781 46

We compared the effect of two selective dopamine D1 receptor agonists, SKF 38393 ((+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol.HCl) and A68930 ((1R,3S)-1-aminomethyl-5,6-dihydroxy-3-phenylisochroman.HCl), and that of imipramine in the behavioural despair model of depression. The dopamine D1 receptor agonists and imipramine showed an anti-immobility effect. Moreover we found that the 'antidepressant' effect of imipramine in the behavioural despair test was antagonized by SCH 23390, a selective dopamine D1 receptor blocker. The results further support the hypothesis that dopamine D1 receptor stimulation plays an important role in the mechanism of action of antidepressants and suggest that dopamine D1 receptor agonists might be considered as potential antidepressant drugs.
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PMID:Antidepressant-like effect of selective dopamine D1 receptor agonists in the behavioural despair animal model of depression. 781 61

The efficacy of d-amphetamine to support a selective bilateral intra-accumbens self-administration response was examined. Bilateral intra-accumbens infusions of d-amphetamine were made contingent upon the acquisition of a lever-pressing response. Two identical levers were available within the operant chamber. Depression of the drug lever resulted in the intra-accumbens delivery of 1 microgram d-amphetamine; responses upon the second, control lever were recorded but had no programmed consequences. Animals were not 'primed' with non-contingent infusions of d-amphetamine at any time during these experiments. Nonetheless, animals readily acquired a selective response upon the drug lever. Removal of the d-amphetamine moiety from the infusate resulted in a large decline in responding, and the abolition of the selectivity of the response for the drug lever. Adulteration of the infusate with either the D1 dopamine receptor antagonist SCH-23390 or the D2 dopamine receptor antagonist sulpiride enhanced the rate of response selectively upon the drug lever. Reductions in the dose of d-amphetamine also increased the rate of response. The effect of co-adulteration of the infusate with both SCH-23390 and sulpiride together was purely additive. The implications of these data for the methodology of intracranial drug self-administration, and the relationship between D1 and D2 dopamine receptors within the nucleus accumbens are discussed.
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PMID:Bilateral intra-accumbens self-administration of d-amphetamine: antagonism with intra-accumbens SCH-23390 and sulpiride. 785 6

The locomotor stimulatory effects of the dopamine D1 receptor partial agonist SKF 38393 were examined in male C57B1/6J mice. Non-habituated mice showed marked dose-related (3-300 mg/kg, SC) locomotor stimulation. The time-course effect was biphasic at very high doses (100-300 mg/kg), with dose-related locomotor depression followed by dose-related long-term hyperlocomotion. For all doses, locomotor effects were detectable throughout the 4-h test period. To determine whether these effects were mediated by D1 receptor stimulation, effects of SKF 38393 were assessed in combination with behaviorally inactive and active doses (0.1 and 0.2 mg/kg, respectively) of the selective D1 receptor antagonist SCH 39166. Both doses of SCH 39166 attenuated the hyperlocomotion induced by 30 mg/kg of the agonist to a similar degree. However, neither dose was able to reverse either the depressant or the stimulatory effects of 300 mg/kg SKF 38393. These results demonstrate effects of the prototypical D1 agonist previously unobserved, and raise questions concerning the nature of agonist/antagonist interactions at the D1 receptor subtype.
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PMID:Biphasic locomotor effects of the dopamine D1 agonist SKF 38393 and their attenuation in non-habituated mice. 787 Sep 1

1. The effects of selective dopamine receptor compounds on the spontaneous activity of single neostriatal neurons were examined extracellularly. 2. Intravenous administration of quinpirole, the D2 agonist, elicited a dose-dependent depression in discharge rate. 3. Quinpirole-evoked depression was reversed by the D2 antagonist eticlopride, but not the D1 antagonist SCH 23390. 4. The partial D1 agonist, SKF 38393 induced depression and excitation in equal proportion. 5. A dose of 0.25 mg/kg SCH 23390 blocked SKF 38393-induced depression but not excitation. 6. SKF 38393-induced excitation was antagonized by eticlopride and in some cases by a higher dose of SCH 23390.
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PMID:Effects of selective dopamine receptor compounds on single, spontaneously-active neostriatal neurons. 789 58

Electrophysiological experiments were conducted in vivo to characterize the involvement of dopamine in effects of cocaine at the cellular level. L-DOPA (preceded by carbidopa) evoked excitation and depression equally at 0.25 mg/kg; however, at 0.5 and 1.0 mg/kg depression in the basal rate of discharge predominated. Cocaine evoked similar responses. At 0.25 and 0.5 mg/kg excitation and depression were elicited in about equal proportion, while at 1.0 mg/kg depression was predominant. Cocaine-induced neuronal changes were reversible by haloperidol. In experiments with specific dopamine antagonists, cocaine-induced neuronal depression was blocked with the D1 antagonist, SCH 23390 at a dose of 0.25 mg/kg. The D2 antagonist, eticlopride, did not alter cocaine-induced depression in any specific manner. Excitation, following cocaine, was not altered by intervention with SCH 23390, yet it was blocked with the D2 antagonist eticlopride at a dose of 0.25 mg/kg. The duration of these changes was consistent with the observed duration of the psychotropic actions of cocaine.
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PMID:Cocaine and dopaminergic actions in rat neostriatum. 841 44

The effects of both the activation and the blockade of D1 or D2 dopamine receptors on long-term depression (LTD) of synaptic transmission, and the involvement of NMDA and GABA receptors in LTD, were investigated in CA1 neurons of rat hippocampal slices. Low-frequency stimulation (LFS, 450 pulses at 1 Hz) produced LTD of the slope of field EPSPs (-14.3%, mean, n = 10). The induction of LTD was blocked by the NMDA receptor antagonist, AP5 (1.4%, n = 7), by the D1 receptor antagonist, SCH-23390 (3.5%, n = 8), or by the D2 receptor agonist, LY-171555 (4.4%, n = 8). Either the activation of D1 receptors by SKF-38393 or the blockade of D2 receptors by sulpiride produced significantly larger LTD than the control LTD (-31.1%, n = 11; -30.6%, n = 9, respectively). Although LTD was blocked by picrotoxin, a GABAA receptor/Cl- channel antagonist (4.9%, n = 8), LTD was produced by LFS in the medium containing both SKF-38393 and picrotoxin (-27.3%, n = 7). These results indicate that: (1) the induction of LTD by LFS in hippocampal CA1 neurons is under the influence of both NMDA and GABA receptors; (2) both D1 and D2 receptors are involved in the modulation of LTD in that the activation of D1 receptors enhances LTD, while that of D2 receptors inhibits LTD, and (3) while the induction of LTD is blocked by picrotoxin, this effect is superseded by SKF-38393.
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PMID:Roles of dopamine receptors in long-term depression: enhancement via D1 receptors and inhibition via D2 receptors. 872 42

1. Whole-cell patch clamp recordings were made from nucleus accumbens neurones in slices of rat ventral forebrain. In the presence of picrotoxin (50 microM), the amplitude of 6-cyano-7-nitroquinoxaline-2, 3-dione-sensitive glutamate EPSCs, recorded at holding potentials between -80 and -90 mV, was reversibly reduced by 56 +/- 11% (n = 6) by dopamine (30 microM). The selective dopamine D1 receptor agonists SKF 38393 (10 microM) and SKF 81297A (10 microM), but not the selective D2 receptor agonist quinpirole (10 microM), also reversibly depressed the EPSC by 36-48%. The depression of the EPSC by dopamine was completely blocked by the D1 receptor antagonist SCH 23390 (1 microM), whereas the D2 antagonist (-)-sulpiride (1 microM) was without effect. 2. EPSCs were reversibly depressed by the dopamine mimetic psychostimulants cocaine (1-20 microM) and amphetamine (10-30 microM) by 40 +/- 16 and 62 +/- 9%, respectively, but only in about half of the cells tested (11/23 and 6/13, respectively). Their actions were completely reversed by SCH 23390 (1 microM), indicating that endogenous dopamine can also depress the EPSC via D1 receptors. 3. No discernable effects of dopamine, SKF 81297A, SKF 38393, quinpirole, cocaine or amphetamine were observed on membrane conductance or holding current (at holding potentials of -80 to -90 mV), suggesting that the depression of the EPSC was solely due to an action on presynaptic D1 receptors. 4. In contrast, agents that elevate intracellular levels of adenosine-3':5'-cyclic monophosphate (cAMP) (forskolin (1-10 microM), 3-isobutyl-1-methylxanthine (0.1-1 mM), rolipram (10 microM), and dibutyryl cAMP (0.5-1 mM)) caused a reversible increase in the EPSC amplitude (by 21-150%). Furthermore, in the presence of forskolin (10 microM), the ability of dopamine to depress synaptic transmission was unaffected. 5. Together these data suggest that both exogenous dopamine and dopamine released from intrinsic nerve terminals attenuate glutamate receptor-mediated synaptic transmission in the nucleus accumbens by presynaptic D1 receptor activation. The transduction mechanism underlying this effect does not appear to involve the formation of cAMP.
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PMID:Endogenous and exogenous dopamine depress EPSCs in rat nucleus accumbens in vitro via D1 receptors activation. 873 May 90


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