Combined treatment of scopolamine and group III mGluR antagonist, CPPG, exerts antidepressant activity without affecting anxiety-related behaviors

2020 ◽  
Vol 224 ◽  
pp. 113034 ◽  
Author(s):  
Mohaddeseh Ebrahimi-Ghiri ◽  
Fatemeh Khakpai ◽  
Mohammad-Reza Zarrindast
Keyword(s):  
Combined Treatment ◽  
Antidepressant Activity ◽  
Group Iii ◽  
Mglur Antagonist

scholarly journals Interaction of Mechanisms Involving Epoxyeicosatrienoic Acids, Adenosine Receptors, and Metabotropic Glutamate Receptors in Neurovascular Coupling in Rat Whisker Barrel Cortex

2007 ◽  
Vol 28 (1) ◽  
pp. 111-125 ◽  
Author(s):  
Yanrong Shi ◽  
Xiaoguang Liu ◽  
Debebe Gebremedhin ◽  
John R Falck ◽  
David R Harder ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Combined Treatment ◽  
Neurovascular Coupling ◽  
Epoxyeicosatrienoic Acids ◽  
Synthesis Inhibitor ◽  
Metabotropic Glutamate ◽  
Whisker Stimulation ◽  
Mglur Antagonist

Adenosine, astrocyte metabotropic glutamate receptors (mGluRs), and epoxyeicosatrienoic acids (EETs) have been implicated in neurovascular coupling. Although A2A and A2B receptors mediate cerebral vasodilation to adenosine, the role of each receptor in the cerebral blood flow (CBF) response to neural activation remains to be fully elucidated. In addition, adenosine can amplify astrocyte calcium, which may increase arachidonic acid metabolites such as EETs. The interaction of these pathways was investigated by determining if combined treatment with antagonists exerted an additive inhibitory effect on the CBF response. During whisker stimulation of anesthetized rats, the increase in cortical CBF was reduced by approximately half after individual administration of A2B, mGluR and EET antagonists and EET synthesis inhibitors. Combining treatment of either a mGluR antagonist, an EET antagonist, or an EET synthesis inhibitor with an A2B receptor antagonist did not produce an additional decrement in the CBF response. Likewise, the CBF response also remained reduced by ∼50% when an EET antagonist was combined with an mGluR antagonist or an mGluR antagonist plus an A2B receptor antagonist. In contrast, A2A and A3 receptor antagonists had no effect on the CBF response to whisker stimulation. We conclude that (1) adenosine A2B receptors, rather than A2A or A3 receptors, play a significant role in coupling cortical CBF to neuronal activity, and (2) the adenosine A2B receptor, mGluR, and EETs signaling pathways are not functionally additive, consistent with the possibility of astrocytic mGluR and adenosine A2B receptor linkage to the synthesis and release of vasodilatory EETs.

scholarly journals The Retino-Hypothalamic Ultrastructural Changes in Traumatic Optic Neuropathy

2021 ◽  
Vol 5 (8) ◽  
Author(s):  
Moyseyenko N
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Optic Neuropathy ◽  
Ganglion Cells ◽  
Neuroprotective Effect ◽  
Combined Treatment ◽  
Ultrastructural Changes ◽  
Traumatic Optic Neuropathy ◽  
Optic Nerves ◽  
Group Iii ◽  
Group I

Aim: To study the retino-hypothalamic ultrastructural changes in traumatic optic neuropathy’s pathogenesis and treatment. Methods: Four groups of mature rabbits were included in this experiment, 30 in each group, 120 in total. The traumatic crush to the optic nerves was reproduced by surgical clips to 90 mature rabbits. The first group (I) included intact/control animals, the second (II) included animals with traumatic optic neuropathy and two other traumatized groups (III and IV) who were given two different doses of treatment. The animals in group III were given infusions of Methylprednisolone 30mg/kg/day for three days. The group IV animals received infusion of 15mg/kg/ day of Methylprednisolone for 3 days in combination with phosphine electric stimulation (PES), starting from the third until the 13th day of the experiment. The electrical pulse which was used on the affected side of the animal was 800 mА and 300 mА on the opposite side. The morphological analysis of the retina and suprachiasmatic nucleus of the hypothalamus of all the four groups of animals included electron microscopy of the semi-thin and ultrathin sections. This analysis was performed a month following the initial injury while the animals were removed from the experiment. The levels of cortisol and adrenocorticotropic hormone (ACTH) in the blood of all experimental animals was tested up to one month following the injury to the optic nerves. Results: We found that trauma to the orbital part of the optic nerve causes collocative necrosis of ganglion cells and swelling of the nerve fiber layer of the ipsilateral retina. In addition, such traumatic damage causes structural changes in the suprachiasmatic nucleus of the hypothalamus. Combined treatment of methylprednisolone with phosphine electro stimulation in traumatized rabbits reduced the thickness of the retina, reduced the cytokaryometric indices and the regeneration processes of bipolar and ganglion cells of the retina. Histopathologically we found an increased number of neurosecretory granules in the suprachiasmatic nucleus of the hypothalamus. ACTH levels in the blood of the group III rabbits were found to be lower, while the cortisol levels higher, and these hormone levels in the IV group rabbits were quite similar to those of the group which was not treated. Conclusion: The combined treatment of traumatic optic neuropathy in rabbits with phosphine electrostimulation and methylprednisolone can be considered a useful treatment, having a beneficial neuroprotective effect.

Loss of Long-Lasting Potentiation Mediated by Group III mGluRs in Amygdala Neurons in Kindling-Induced Epileptogenesis

1997 ◽  
Vol 78 (6) ◽  
pp. 3475-3478 ◽  
Author(s):  
Volker Neugebauer ◽  
N. Bradley Keele ◽  
Patricia Shinnick-Gallagher
Keyword(s):  
Electrical Stimulation ◽  
Synaptic Transmission ◽  
Learning And Memory ◽  
Metabotropic Glutamate Receptors ◽  
Long Term Potentiation ◽  
Group Iii ◽  
Brain Functions ◽  
Group Ii ◽  
Mglur Antagonist

Neugebauer, Volker, N. Bradley Keele, and Patricia Shinnick-Gallagher. Loss of long-lasting potentiation mediated by group III mGluRs in amygdala neurons in kindling-induced epileptogenesis. J. Neurophysiol. 78: 3475–3478, 1997. Long-lasting modifications of synaptic transmission can be induced in the amygdala by electrical stimulation as done in the long-term potentiation (LTP) model of learning and memory and the kindling model of epilepsy. The present study reports for the first time a long-lasting potentiation (LLP) of synaptic transmission that is induced pharmacologically by the activation of group III metabotropic glutamate receptors (mGluRs) in basolateral amygdala (BLA) neurons. In whole cell voltage-clamp mode, BLA neurons were recorded in brain slices from control rats and rats with amygdala-kindled seizures. The group III mGluR agonist l-2-amino-4-phosphonobutyrate (l-AP4, 10 μM) induced LLP of monosynaptic excitatory postsynaptic currents (EPSCs) evoked by electrical stimulation in the lateral amygdala (maximum 258 ± 50% of predrug control; means ± SE) in control ( n = 7) but not in kindled neurons( n = 6). LLP was measured 15 min after the superfusion of l-AP4, lasted for >45 min, and was not accompanied by postsynaptic membrane changes. l-AP4 induced LLP was prevented by the group III mGluR antagonist (S)-2-methyl-2-amino-4-phosphonobutyrate (MAP4; 100 μM, n = 6) but not the group II mGluR antagonist (2S,3S,4S)-2-methyl-2-carboxycyclopropylglycine (MCCG; 100 μM, n = 3). LLP was not observed after superfusion of the group II mGluR agonist (2S,3S,4S)-2-(carboxycyclopropyl)glycine (l-CCG; 1.0 and 10 μM) in either control ( n = 13) or kindled ( n = 10) neurons. If the underlying mechanisms and the functional significance of pharmacologically induced LLP are similar to those of LTP, the loss of l-AP4 induced LLP in kindled neurons may be a neurobiological correlate of learning and memory deficits in kindled animals and long-term alterations of brain functions in patients with epilepsies.

MYOCARDIAL SALVAGE BY COMBINED TREATMENT WITH RECOMBINANT SINGLE-CHAIN UROKINASE-TYPE PLASMINOGEN ACTIVATOR AND RECOMBINANT HUMAN SUPEROXIDE DISMUTASE IN A CANINE CORONARY THROMBOSIS MODEL*

1987 ◽  
Author(s):  
U Finke ◽  
J Schneider ◽  
E Friderichs ◽  
L Flohé ◽  
H Giertz
Keyword(s):  
Combined Treatment ◽  
Myocardial Salvage ◽  
Single Chain ◽  
Reperfusion Arrhythmias ◽  
Group Iii ◽  
Thrombosis Model ◽  
Group I ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Group Ii

Recanalization of thrombotic coronary occlusion with fibrinolytic treatment is a promising approach to salvage jeopardized ischemic myocardium. However, the success of thrombolytic treatment of myocardial infarction may be curtailed by the risk inherent to reperfusion. Cell damage upon reoxygenation after an ischemic period is tentatively attributed to the formation of oxygen-derived free radicals. Improved myocardial salvage is therefore expected from coadministration of a free radical scavenger and fibrinolytic treatment. We tested this hypothesis in a canine model of left anterior circumflex coronary artery (LCX) thrombosis. Thrombolysis was achieved with the fibrin- selective single-chain urokinase-type plasminogen activator of recombinant origin (r-scu-PA). As enzymatic scavenger of oxygen radicals recombinant human superoxide dismu-tase (r-HSOD) was used. The three experimental groups were: group I (n=4) did not receive any treatment after LCX thrombosis; in group II (n=9) at 100 min after LCX thrombosis r-scu-PA (20 μg/kg/min i.v. for 30 min) was infused; dogs in group III (n=8) received concomitant treatment with r-scu-PA and r-HSOD (10 mg/kg i.v. for 60 min). Infarct size as percent of the risk zone was 38.2 ± 4.1 in group I, 25.3 ± 3.7 in group II (p ≤ 0.05 vs group I) and 14.9 ± 3.2 in group III (p ≤ 0.05 vs group II). Incidence of reperfusion arrhythmias and increase in plasma CK were significantly diminished by r-HSOD when compared to dogs receiving r-scu-PA only. There were no significant differences in hemodynamic parameters between the groups. In conclusion, in terms of infarct size reduction, suppression of reperfusion arrhythmias and attenuation of intracellular enzyme release the combined treatment with r-scu-PA and r-HSOD yielded a significant higher myocardial salvage versus thrombolytic treatment alone in a canine LCX thrombosis model.* This work is part of the doctoral dissertation of Miss U. Fincke

scholarly journals Evaluation of antidepressant activity of tramadol in albino mice using forced swim model

2019 ◽  
Vol 8 (3) ◽  
pp. 415
Author(s):  
Ramachandra K. ◽  
Jayalakshmi M. D.
Keyword(s):  
Animal Studies ◽  
Antidepressant Activity ◽  
Antidepressant Effect ◽  
10Mg Dose ◽  
Group Iii ◽  
Forced Swim ◽  
Group I ◽  
Immobility Time ◽  
Albino Mice ◽  
Group Ii

Background: The fact that tramadol can be used as an antidepressant, has been already proved by some animal studies. The objective of the present study was to evaluate antidepressant activity of tramadol in albino mice using forced swim model.Methods: Forced swimming test (FST) model was used to evaluate the antidepressant effect. Mice in the group "I" were given normal saline. Mice in the group II were given imipramine. Mice in the group III were given tramadol 10mg/kg. Mice in the group IV were given tramadol 20mg/kg. Mice in the group V were given tramadol 40mg/kg. All doses in all groups were given by intra peritoneum route.Results: The average values of immobility in group I were higher significantly compared to group III, IV and V. The values of group I and group II were found to be comparable. It was found that the baseline mean value was 196.33 which reduced to 5.16 with the effect of imipramine where imipramine was given to those mice. But in tramadol 10mg group, it was highest, and it came down to 40.66 and as the dose of tramadol was increased, the immobility time reduced from 40.66 at 10mg dose to 31.33 at 20mg dose and finally to 13.33mg at 40mg dose.Conclusions: Considering the results of two different animal models of depression it can be concluded that Tramadol has antidepressant activity at 10mg, 20mg, 40mg which was almost similar to Imipramine.

scholarly journals Antiinflammatory therapy of neurotrophic corneal diseases

2019 ◽  
Vol 12 (4) ◽  
pp. 77-82
Author(s):  
E. V. Yani ◽  
E. N. Orlova ◽  
V. A. Golikova
Keyword(s):  
Combined Treatment ◽  
Eye Drops ◽  
Test Results ◽  
Antiinflammatory Therapy ◽  
Group Iii ◽  
Group I ◽  
New Directions ◽  
Neurotrophic Keratitis ◽  
Anti Inflammatory ◽  
Group Ii

Clinical data on new directions in combined treatment of neurotrophic keratitis, including anti-inflammatory therapy are presented.Purpose. To compare the effectiveness of bromfenac 0.09 %, nepafenac 0.1 % and indomethacin 0.1 % eye drops in the treatment of neurotrophic keratitis (NK).Materials and methods. 22 NK patients, aged 34 to 78, were divided into three groups. Group I received bromfenac 0.09 %, group II, nepafenac 0.1 %, and group III, indomethacin 0.1 %. Ophthalmic tests included visometry, biomicroscopy, corneal sensitivity determination, as well as diagnostic tests to determine indicators of tear production (Schirmer test, Norn test, LIPCOF test), and measuring lacrimal meniscus height.Results. Between visits V2 and V3, patients of group III showed an increase in conjunctival irritation to an average of 2.3 points, while groups I and II revealed the condition of the conjunctiva at 0.9 and 1.1 points, respectively. The lesion area was evaluated in points (max = 20) and averaged on V1 6.8 points in group I, 5.9 points in group II and 7.2 points in group III. Keratopathy in group I which was estimated at 3.8 points before V2, dropped to 1.4 points by V3. In group III it was 1.7 points by V3. In group II, keratopathy showed only 4.1 points by V3. The average Norn test on the day of treatment showed 2.7 seconds in group I, 2.5 seconds in group II, and 3.1 seconds in group III. No significant increase in Schirmer's test results in all groups was recorded.Conclusion. The use of non-steroidal anti-inflammatory eye drops of various groups — bromfenac 0.09%, nepafenac 0.1 % and indomethacin 0.1 % — gave a positive result in NK therapy. However, bromfenac 0.09% instillations administered once a day produce a higher anti-inflammatory effect then the same quantity of nepafenac 0.1% and indomethacin 0.1 % instillations.

scholarly journals Astrocyte activation of presynaptic metabotropic glutamate receptors modulates hippocampal inhibitory synaptic transmission

2004 ◽  
Vol 1 (4) ◽  
pp. 307-316 ◽  
Author(s):  
QING-SONG LIU ◽  
QIWU XU ◽  
JIAN KANG ◽  
MAIKEN NEDERGAARD
Keyword(s):  
Synaptic Transmission ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Group Iii ◽  
Inhibitory Synaptic Transmission ◽  
Metabotropic Glutamate ◽  
Group Ii ◽  
Mglur Antagonist

In the CNS, fine processes of astrocytes often wrap around dendrites, axons and synapses, which provides an interface where neurons and astrocytes might interact. We have reported previously that selective Ca2+ elevation in astrocytes, by photolysis of caged Ca2+ by o-nitrophenyl-EGTA (NP-EGTA), causes a kainite receptor-dependent increase in the frequency of spontaneous inhibitory post-synaptic potentials (sIPSCs) in neighboring interneurons in hippocampal slices. However, tetrodotoxin (TTX), which blocks action potentials, reduces the frequency of miniature IPSCs (mIPSCs) in interneurons during Ca2+ uncaging by an unknown presynaptic mechanism. In this study we investigate the mechanism underlying the presynaptic inhibition. We show that Ca2+ uncaging in astrocytes is accompanied by a decrease in the amplitude of evoked IPSCs (eIPSCs) in neighboring interneurons. The decreases in eIPSC amplitude and mIPSC frequency are prevented by CPPG, a group II/III metabotropic glutamate receptor (mGluR) antagonist, but not by the AMPA/kainate and NMDA receptor antagonists CNQX/CPP. Application of either the group II mGluR agonist DCG IV or the group III mGluR agonist L-AP4 decreased the amplitude of eIPSCs by a presynaptic mechanism, and both effects are blocked by CPPG. Thus, activation of mGluRs mediates the effects of Ca2+ uncaging on mIPSCs and eIPSCs. Our results indicate that Ca2+-dependent release of glutamate from astrocytes can activate distinct classes of glutamate receptors and differentially modulate inhibitory synaptic transmission in hippocampal interneurons.

scholarly journals Effect of hyaluronate and splinting alone versus combined treatment (splinting and hyaluronate) on thumb carpometacarpal osteoarthritis

2020 ◽  
Vol 2 (1) ◽  
pp. 35-40
Author(s):  
Salvatore Denaro ◽  
Salvatore Boccaccio ◽  
Antonino Zocco
Keyword(s):  
Grip Strength ◽  
Rating Scale ◽  
Combined Treatment ◽  
Numeric Rating Scale ◽  
Group Iii ◽  
Pain Disability ◽  
Group I ◽  
Group Ii ◽  
Thumb Carpometacarpal ◽  
Carpometacarpal Osteoarthritis

Thumb carpometacarpal osteoarthritis can lead to global hand dysfunctions and its symptoms are pain and inability. The purpose of this study is to determine the effectiveness of hyaluronate in relieving these symptoms, and to compare it to orthosis and combined treatment (orthosis and hyaluronate). We enrolled 39 patients, evaluated at the baseline by using numeric rating scale (NRS) for pain, Disability of the Arm, Shoulder and Hand (DASH) and Dreiser Scale for disability degree, and Digital Hydraulic Pinch Gauge for grip strength. Eligible participants were randomly assigned to one of the three treatments: injection of hyaluronate (group I), combined treatment (hyaluronate and orthosis, Group II) and orthosis (hard-resting splint, Group III). Patients of Group I and Group II were injected by low molecular weight Hyaluronate once a week for three consecutive weeks. Injections were performed by means of the so-called blind technique. The data analysis indicated a significant decrease (P<0.01) of pain at week 4, further manifested at week 26 by all groups treated. The same occurred for functional symptoms, and grip strength. This improvement appears more evident in group I that received HA.

scholarly journals The effectiveness of treatment of cervical spine pathologies associated with undifferentiated connective tissue dysplasia in children

2020 ◽  
Vol 24 (5) ◽  
pp. 312-316
Author(s):  
S. M. Sharkov ◽  
Eugenia E. Tabe
Keyword(s):  
Cervical Spine ◽  
Connective Tissue ◽  
Standard Treatment ◽  
Combined Treatment ◽  
Structural Features ◽  
Treatment Modalities ◽  
Group Iii ◽  
Group I ◽  
Spine Pathology ◽  
Connective Tissue Dysplasia

Introduction. The article background a necessity to timely perform conservative treatment of cervical spine pathologies associated with undifferentiated connective tissue dysplasia in children. Their treatment should consider all structural features of the cervical spine, its blood supply and concomitant pathologies which may be identified by diagnostic algorithms of multidisciplinary approach. Material and methods. In 2018-2020, 177 children with cervical spine pathologies associated with undifferentiated connective tissue dysplasia were conservatively treated in Morozovskaya Children’s City Clinical Hospital. All children were randomized into 3 groups which were prescribed different treatment modalities. In Group I, patients had standard treatment (exercise therapy, isometric gymnastics, massage, apparatus therapy); in Group II, head holders were added to standard treatment; in Group III, medicamentous therapy was added to standard treatment and head holders (magnesium lactate dihydrate and pyridoxine hydrochloride, levocarnitine). The instrumental examination revealed that all studied children had phenotypic signs of syndromes of undifferentiated connective tissue dysplasia and signs of pathology in the cervical spine. The average follow-up period was 24 months (6 months - 2 years). The average age of patients was 10 ± 3 years (5-17 years). Results and discussion. In order to assess the effectiveness of treatment, a comparative analysis of findings obtained at objective examinations was made before treatment and in 6 and 12 months after it. The examinations included: measurements of linear blood flow velocity in the vertebral arteries with ultrasound Doppler of the brachycephalic vessels; X-ray measurements of the cervical spine (Cruvelier joint and various displacements in vertebrae). The analysis performed has shown that the best results were registered in Group III. Conclusion. Findings obtained after catamnestic and instrumental examinations have showed that the complex treatment of cervical spine pathology, associated with undifferentiated connective tissue dysplasia in children, should include not only standard treatment (physical exercise trainings, massage, apparatus therapy) but also cervical orthoses and medicamentous therapy. Such a combined treatment has more pronounced therapeutic effect.

Combined effects of niacin and chromium treatment on heart of hyperlipidemic rats

2010 ◽  
Vol 30 (10) ◽  
pp. 1561-1566 ◽  
Author(s):  
M Mutluhan Döger ◽  
Bahar B Sokmen ◽  
Refiye Yanardag
Keyword(s):  
Combined Treatment ◽  
Heart Tissue ◽  
Protein Carbonyl ◽  
Group Iv ◽  
Albino Rats ◽  
Gamma Glutamyl Transferase ◽  
Group Iii ◽  
Group I ◽  
Glutamyl Transferase ◽  
Serum Paraoxonase

The present study was undertaken to investigate the effects of the combination of niacin and chromium(III)-chloride on heart glutathione (GSH), lipid peroxidation (LPO) levels, serum paraoxonase (PON), gamma-glutamyl transferase (GGT) activities and protein carbonyl contents (PCC) of hyperlipidemic rats. In this study, female Swiss albino rats were used. They were divided into four groups. The animals of the first group (group I) were fed with pellet chow. The rats (group II) were fed with a lipogenic diet consisting of 2% cholesterol, 0.5% cholic acid and 20% sunflower oil added to the pellet chow, and given 3% alcoholic water for 60 days. The rats (group III) were fed with the same lipogenic diet and treated by gavage technique with CrCl3 6H2O to a dose of 250 µg/kg and 100 mg/kg niacin for 45 days, 15 days after experimental animals were done hyperlipidemic. Group IV was fed with pellet chow and treated with 250 µg/kg CrCl3 6H2O and 100 mg/kg niacin for 45 days. On the 60th day, the heart tissue and blood samples were taken from animals. As a result, heart LPO, serum GGT activity and serum PCC were increased; serum PON activity and heart GSH levels were decreased in hyperlipidemic rats. Treatment with combined niacin and chromium reversed these effects. In conclusion, the combined treatment with niacin and chromium might induce a protective effect on heart tissue.

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