UMLS:C0011570 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies indicate that dopamine modulates the excitability of the respiratory network and its susceptibility to depression by exogenous opioids, but the roles of different subtypes of dopamine receptor in these processes are still uncertain. In this study, D1-dopamine receptor (D1R) involvement in dopaminergic modulation of respiratory rhythm and mu-opioid receptor mediated depression were investigated in pentobarbital-anesthetized cats. Intravenous administration of the D1R blocker SCH-23390 (100-200 microg/kg) slowed phrenic nerve and expiratory neuron respiratory rhythms by prolonging the inspiratory and expiratory phases. Phrenic nerve discharge intensity also increased more gradually during the inspiratory phase. SCH-23390 (150 microg/kg) also enhanced dose-dependent depression of phrenic nerve and expiratory neuron excitability, as well as rhythm disturbances, produced by the mu-opioid receptor agonist fentanyl (2-20 microg/kg, i.v.). The results suggest an important role for the D1-subtype of receptor in respiratory rhythm modulation, and indicate that this type of receptor participates in dopaminergic compensatory mechanisms directed against opioid-mediated network depression.
...
PMID:D1-dopamine receptor blockade slows respiratory rhythm and enhances opioid-mediated depression. 1565 84

Long-term potentiation (LTP) of C-fiber-evoked field potentials in spinal dorsal horn may be relevant to pathological pain. Our previous work has shown that the late phase of the spinal LTP is protein synthesis-dependent. Considerable evidence has accumulated that dopamine D1/D5 receptors are important for late-phase LTP in hippocampus. In this study, the role of D1/D5 receptors in LTP of C-fiber-evoked field potentials in spinal dorsal horn was evaluated in urethan-anesthetized Sprague-Dawley rats. We found the following. 1) Spinal application of SKF 38393, a D1/D5 receptor agonist, induced a slowly developed LTP of C-fiber-evoked field potentials, lasting for >10 h, and the effect was blocked by the D1/D5 antagonist SCH 23390, whereas a D2 receptor agonist (quinpirole) induced depression of C-fiber responses, lasting for 2 h. 2) The potentiation produced by D1/D5 receptor agonist occluded the late phase but not the early phase of the spinal LTP produced by tetanic stimulation. 3) SCH 23390 selectively depressed the late-phase LTP, when applied 40 min before tetanic stimulation. 4) The D1/D5 agonist-induced potentiation is blocked by the protein synthesis inhibitor anisomycin. 5) Activation of protein kinase A by spinal application of 8-Br-cAMP also induced spinal LTP, and the action occluded the potentiation induced by the D1/D5 receptor agonist. These results suggest that the spinal D1/D5 receptors participate in the protein synthesis-dependent late-phase LTP of C-fiber-evoked field potentials in spinal dorsal horn through the cAMP signaling pathway.
...
PMID:Activation of spinal d1/d5 receptors induces late-phase LTP of C-fiber-evoked field potentials in rat spinal dorsal horn. 1582 90

Approximately 70% of tobacco smokers wish to quit, but attempts are often unsuccessful partly due to the aversive nicotine withdrawal syndrome. We investigated the possible involvement of nicotinic and dopaminergic signalling in the central nucleus of the amygdala (CeA) and dorsolateral bed nucleus of the stria terminalis (dlBNST) in the anhedonic depression-like effect of precipitated nicotine withdrawal in rats. Nicotine-dependent rats exhibit elevations in intracranial self-stimulation (ICSS) thresholds compared to control rats after cessation of chronic nicotine administration (spontaneous withdrawal) or systemic or intra-ventral tegmental area (VTA), but not intra-nucleus accumbens (NAcc), administration of nicotinic acetylcholine receptor (nAchR) antagonists while exposed to nicotine (precipitated withdrawal). We examined whether intracerebral administration of the nAChR antagonist dihydro-beta-erythroidine (DHbetaE; 0.6-20 microg total bilateral dose) or the dopamine D1-like receptor antagonist SCH 23390 (2-16 microg total bilateral dose) into the CeA and dlBNST results in withdrawal-like threshold elevations in nicotine-treated rats. Nicotinic acetylcholine and D1-like receptor blockade in the CeA or the dlBNST did not induce differential threshold elevations in nicotine- and saline-treated rats. Further, the highest SCH 23390 dose (16 microg bilateral dose) injected into the dlBNST, but not the CeA, elevated thresholds similarly in both saline- and nicotine-treated rats, suggesting that dopaminergic signalling in the dlBNST may regulate brain reward function under baseline conditions. These results suggest that nACh and D1-like signalling in the CeA and the dlBNST does not develop neuroadaptations with the development of nicotine dependence that may be involved in the depression-like aspects of nicotine withdrawal.
...
PMID:Blockade of nicotinic acetylcholine or dopamine D1-like receptors in the central nucleus of the amygdala or the bed nucleus of the stria terminalis does not precipitate nicotine withdrawal in nicotine-dependent rats. 1656 23

The neuropeptide corticotropin-releasing factor (CRF) is believed to play a role in a number of psychiatric conditions, including anxiety disorders and depression. In the present study, male Sprague Dawley rats were used to examine the behavioral effects of altering dopamine transmission on CRF-enhanced startle, a behavioral assay believed to reflect stress- or anxiety-like states. Systemic administration of the selective dopamine D1 receptor antagonist SCH 23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride] (0, 0.01, 0.05, 0.1, 0.5 mg/kg) dose dependently blocked the effect of CRF (1 microg, i.c.v.) on startle at doses that had no effect on baseline startle response. Immunohistochemical studies showed that most CRF-containing cells in the dorsolateral division of the bed nucleus of the stria terminalis (BSTld), part of the critical brain area mediating CRF-enhanced startle, are surrounded by a dense plexus of tyrosine hydroxylase (TH)-positive fibers. Intra-BSTld injections of the retrograde tracer Fluorogold (FG) into the TH field identified neurons in the major dopaminergic areas (A8-A10), but not the major noradrenergic areas [A5, A6 (locus ceruleus), A7], as a significant source of TH-positive innervation. The majority of FG-filled cells double-labeled for TH were found in the dorsocaudal A10 cell group (A10dc) located in the periaqueductal gray area. Together, these data suggest that neuronal regulation of the BSTld by specific dopaminergic pathways and receptors may be an important mechanism for controlling CRF-dependent moods and affective states. These data also suggest that compounds with D1 receptor antagonist properties might have anxiolytic-like effects that could be useful for treating conditions associated with hyperactive CRF systems.
...
PMID:Behavioral and anatomical interactions between dopamine and corticotropin-releasing factor in the rat. 1659 40

The lateral septal nucleus receives a diffuse dopaminergic input originating from the ventral tegmental area of the brain stem. We examined whether dopamine (DA) modulates synaptic transmission in the slice preparation of the rat dorsolateral septal nucleus (DLSN). Bath application (10-15 min) of DA (30 muM) markedly depressed the amplitude of fast and slow inhibitory postsynaptic potentials (IPSPs) in DLSN neurons, while it produced only a minor depression of the amplitude of excitatory postsynaptic potentials (EPSPs) obtained in the presence of bicuculline. DA (30 muM) depressed the monosynaptic fast IPSP to approximately 50% of control, but did not depress the inward current (I(GABA)) induced by exogenous gamma-aminobutyric acid (GABA). DA decreased the frequency of miniature fast IPSPs (m-fIPSPs) without significantly changing their amplitude. PD 168077, a selective D4 receptor agonist, depressed the fast and slow IPSPs but not the EPSP and decreased the frequency of m-fIPSPs. Both DA and PD 168077 increased the paired-pulse ratio of the monosynaptic fast IPSP. The inhibitory effect of DA on the fast IPSP was significantly attenuated by L-741,742, an antagonist at D4 receptors, but not by SCH 23390 and sulpiride, a D1-like and a D2-like receptor antagonist, respectively. N-ethylmaleimide, a blocker of pertussis toxin (PTX)-sensitive G protein (G(i/o)), attenuated the DA-induced depression of the fast IPSP. N-[2-((p-bromocinnamyl) amino)ethyl]-5-isoquinoline sulfonamide, a protein kinase A (PKA) inhibitor, attenuated the DA-induced depression of the fast IPSP. These results suggest that DA inhibits spontaneous and evoked release of GABA via the D4 receptor-G(i)-protein-PKA system in DLSN neurons.
...
PMID:Dopamine presynaptically depresses fast inhibitory synaptic transmission via D4 receptor-protein kinase A pathway in the rat dorsolateral septal nucleus. 1664 81

In the somatosensory system, the flow of sensory information is regulated at early stages by presynaptic inhibition. Recent findings have shown that the mechanisms generating the primary afferent depolarization (PAD) associated with presynaptic inhibition are complex, with some components mediated by a non-spiking mechanism. How sensory inputs carried by neighbouring afferent fibres interact to regulate the generation of PAD, and thus presynaptic inhibition, is poorly known. Here, we investigated the interaction between neighbouring primary afferents for the generation of PAD in an in vitro preparation of the turtle spinal cord. To monitor PAD we recorded the dorsal root potential (DRP), while the simultaneous cord dorsum potential (CDP) was recorded to assess the population postsynaptic response. We found that the DRP and the CDP evoked by a primary afferent test stimulus was greatly reduced by a conditioning activation of neighbouring primary afferents. This depression had early and late components, mediated in part by GABAA and GABAB receptors, since they were reduced by bicuculline and SCH 50911 respectively. However, with the selective stimulation of C and Adelta fibres in the presence of TTX, the early and late depression of the DRP was replaced by facilitation of the GABAergic and glutamatergic components of the TTX-resistant DRP. Our findings suggest a subtle lateral excitatory interaction between primary afferents for the generation of PAD mediated by a non-spiking mechanism that may contribute to shaping of information transmitted by C and Adelta fibres in a spatially confined scale in analogy with the retina and olfactory bulb.
...
PMID:Heterosynaptic modulation of the dorsal root potential in the turtle spinal cord in vitro. 1698 51

The striatum is critically important in motor, cognitive and emotional functions, as highlighted in neurological disorders such as Huntington's disease (HD) where these functions are compromised. The R6/2 mouse model of HD shows progressive motor and cognitive impairments and alterations in striatal dopamine and glutamate release. To determine whether or not dopamine-dependent neuronal plasticity is also altered in the dorsolateral striatum of R6/2 mice, we compared long term potentiation (LTP) and long term depression (LTD) in striatal slices from R6/2 mice with that seen in slices from wild type (WT) mice. In adult WT mice (aged 8-19 weeks), frequency-dependent bidirectional plasticity was observed. High frequency stimulation (four 0.5 s trains at 100 Hz, inter-train interval 10 s) induced LTP (134+/-5% of baseline), while low frequency stimulation (4 Hz for 15 min) induced LTD (80+/-5% of baseline). LTP and LTD were significantly blocked by the N-methyl-D-aspartic acid (NMDA) receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) (to 93+/-6% and 103+/-8% of baseline respectively), indicating that they are both dependent on NMDA glutamate receptor activation. LTP was significantly blocked by the dopamine D1 receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH-23390) (98+/-8% of baseline), indicating that LTP is dependent on activation of dopamine D(1)-type receptors, whereas LTD was not significantly different (90+/-7%). In adult R6/2 mice (aged 8-19 weeks), LTP was significantly reduced (to 110+/-4% of baseline), while LTD was not significantly different from that seen in WT mice (85+/-6%). These data show that R6/2 mice have impaired dopamine-dependent neuronal plasticity in the striatum. As dopamine-dependent plasticity is a proposed model of striatum-based motor and cognitive functions, this impairment could contribute to deficits seen in R6/2 mice.
...
PMID:Dopamine-dependent long term potentiation in the dorsal striatum is reduced in the R6/2 mouse model of Huntington's disease. 1747 55

Multiple lines of investigation have explored the role of dopaminergic systems in mental depression. Chronic treatment with antidepressant drugs has been reported to alter dopaminergic neurotransmission, most notably a sensitization of behavioural responses to agonists acting at D2/D3 dopamine receptors within the nucleus accumbens. Recent clinical evidences have shown that ropinirole, a D2/D3 dopamine receptor agonist, augments the action of various standard antidepressant drugs in treatment-resistant depression. The present study was undertaken to elucidate the possible mechanism of antidepressant action of ropinirole employing various behavioral paradigms of despair supported by the measurements of neurochemical changes in the tissue contents of dopamine (DA) and serotonin (5-HT) in the whole brain using high-performance-liquid chromatography (HPLC) with electrochemical detectors (ECD). In the mouse forced swim test (FST) or tail-suspension test (TST), ropinirole (1-10 mg/kg, i.p.) produced S-shaped dose-response curve in the percentage decrease in immobility period. Compared with vehicle, ropinirole (10 mg/kg., i.p.) had a significant anti-immobility effect without affecting locomotor activity. The reduction in the immobility period elicited by ropinirole (10 mg/kg, i.p.) in the FST was reversed by dopaminergic and sigma receptor antagonist, haloperidol (0.5 mg/kg, i.p.), and specific D2 dopamine receptor antagonist sulpiride (5 mg/kg i.p.), but not by SCH 23390 (0.5 mg/kg i.p), a D1 dopamine receptor antagonist. Rimcazole (5 mg/kg i.p.) (a sigma receptor antagonist), progesterone (10 mg/kg i.p.) (a sigma receptor antagonistic neurosteroid), BD 1047 (1 mg/kg i.p.) (a novel sigma receptor antagonist with preferential affinity for sigma-1 sites) also reversed the anti-immobility effect of ropinirole (10 mg/kg i.p.). The neurochemical studies of whole brain revealed that ropinirole at 10 mg/kg i.p. did not affect the tissue levels of dopamine but significantly increased serotonin levels. The study indicated that ropinirole possessed anti-immobility activity in FST by altering dopaminergic, serotonergic or sigma receptor function.
...
PMID:Involvement of dopamine (DA)/serotonin (5-HT)/sigma (sigma) receptor modulation in mediating the antidepressant action of ropinirole hydrochloride, a D2/D3 dopamine receptor agonist. 1768 90

Preclinical evidence strongly implicates GABA(B) receptors in the pathophysiology of several psychiatric disorders including anxiety and depression. In the present study, we investigated the effects of the selective GABA(B) receptor agonists baclofen and SKF 97541, the GABA(B) receptor positive allosteric modulator CGP7930 and the GABA(B) receptor antagonist SCH 50911 in the modified forced swimming test (FST) and in the elevated zero maze test (EZM), i.e. in animal models predictive of antidepressant and antianxiety activities, respectively. The classical antidepressant imipramine and the anxiolytic diazepam were employed as control drugs in the FST and in the EZM, respectively. In the FST, baclofen (0.25 mg/kg), SKF 97541 (0.01-0.05 mg/kg) or CGP 7930 (1-3 mg/kg) and SCH 50911 (1-3 mg/kg) showed antidepressant-like activity, significantly decreasing immobility time; these effects were not related to changes in locomotor activity. The antidepressant effects produced by the GABA(B) receptor ligands were compared with that of imipramine (30 mg/kg). In the EZM, CGP 7930 (1 mg/kg) and SCH 50911 (1-3 mg/kg) produced anxiolytic-like effects, significantly increasing time spent in the open areas of the maze; those effects were comparable with the effects of diazepam (1-2 mg/kg). Our results indicate that differential manipulation of GABA(B) receptors can modify behaviors relevant to depression and anxiety. The GABA(B) receptor positive allosteric modulator CGP 7930 and the antagonist SCH 50911 show both antidepressant and anxiolytic profile, while the GABA(B) receptor agonists (baclofen and SKF 97541) produce effects that are characteristic of antidepressant drugs.
...
PMID:Effects of GABAB receptor ligands in animal tests of depression and anxiety. 1819 53

Long-term changes in the efficacy of glutamatergic synaptic transmission in the striatal complex are proposed to underlie motor learning and neuroadaptations leading to addiction. Dopamine and glutamate play key roles in the induction of long-term potentiation (LTP) and long-term depression (LTD) in the dorsal striatum, but their contribution to synaptic plasticity in the ventral striatum (nucleus accumbens, NAc) has been less extensively studied. We have examined the role of dopamine, glutamate and GABA in the induction of LTP in mouse brain slices containing the NAc. High-frequency stimulation of glutamatergic inputs elicited LTP of field excitatory postsynaptic potentials/population spikes (fEPSP/PSs) in the core region of the NAc. GABA did not seem to participate in LTP induction because LTP was not altered in the presence of either a GABA(A)- (bicuculline) or a GABA(B)- (CGP 55845) receptor antagonist. However, the dopamine D1 receptor antagonist SCH 23390, but not the dopamine D2 receptor antagonist sulpiride, impaired LTP. The dopamine reuptake blocker nomifensine also inhibited LTP induction. We found that group I metabotropic glutamate receptors (mGluRs) contribute to LTP induction because the mGluR1 antagonist LY 367385, or the mGluR5 antagonist MPEP, blocked LTP induction. Furthermore, the glutamate reuptake blocker DL-TBOA also impaired LTP. The present results demonstrate that dopamine and glutamate play critical roles in the mechanisms of induction of LTP in the NAc through the activation of dopamine D1 receptors and group I mGluRs. However, LTP is negatively regulated when endogenous levels of dopamine or glutamate are elevated.
...
PMID:Dopamine D1 receptors and group I metabotropic glutamate receptors contribute to the induction of long-term potentiation in the nucleus accumbens. 1827 87

<< Previous 1 2 3 4 5 6 7 8 9 Next >>