scholarly journals Risperidone and 5-HT2A Receptor Antagonists Attenuate and Reverse Cocaine-Induced Hyperthermia in Rats

2020 ◽  
Vol 23 (12) ◽  
pp. 811-820
Author(s):  
Tsuyoshi Okada ◽  
Katsutoshi Shioda ◽  
Akiko Makiguchi ◽  
Shiro Suda
Keyword(s):  
In Vivo Microdialysis ◽  
D1 Receptor ◽  
D1 Receptors ◽  
Receptor Antagonists ◽  
Induced Hyperthermia ◽  
Definitive Therapy ◽  
Before And After ◽  
Sch 23 390 ◽  
Related Mortality

Abstract Background Cocaine (benzoylmethylecgonine) is one of the most widely used illegal psychostimulant drugs worldwide, and mortality from acute intoxication is increasing. Suppressing hyperthermia is effective in reducing cocaine-related mortality, but a definitive therapy has not yet been found. In this study, we assessed the ability of risperidone to attenuate acute cocaine-induced hyperthermia and delineated the mechanism of its action. Methods Rats were injected i.p. with saline, risperidone, ketanserin, ritanserin, haloperidol, or SCH 23 390 before and after injection of cocaine (30 mg/kg) or with WAY-00 635, SB 206 553, or sulpiride before cocaine injection; thereafter, the rectal temperature was measured every 30 minutes for up to 4 hours. In vivo microdialysis was used to reveal the effect of risperidone on cocaine-induced elevation of dopamine (DA), serotonin (5-HT), and noradrenaline concentrations in the anterior hypothalamus. For post-administration experiments, saline or risperidone (0.5 mg/kg) were injected into rats, and cocaine (30 mg/kg) was injected 15 minutes later. For every 30 minutes thereafter, DA, 5-HT, and noradrenaline levels were measured for up to 240 minutes after cocaine administration. Results Risperidone, 5-HT2A receptor antagonists, and D1 receptor antagonistic drugs prevented and reversed cocaine-induced hyperthermia. In contrast, receptor antagonists for 5-HT1A, 5-HT2B/2C, and D2 did not alter cocaine-induced hyperthermia. Risperidone treatment further attenuated cocaine-induced elevation of DA. Conclusions Our results indicate that risperidone attenuates cocaine-induced hyperthermia primarily by blocking the activities of the 5-HT2A and D1 receptors and may be potentially useful for treating cocaine-induced acute hyperthermia in humans.

In vivo microdialysis measurement of histamine in rat blood effects of compound 48/80 and histamine receptor antagonists

1993 ◽  
Vol 29 (2) ◽  
pp. 105-109 ◽  
Author(s):  
Eiichi Sakurai ◽  
Eri Gunji ◽  
Yukisumi Iizuka ◽  
Noboru Hikichi ◽  
Kazutaka Maeyama ◽  
...  
Keyword(s):  
Histamine Receptor ◽  
In Vivo Microdialysis ◽  
Receptor Antagonists ◽  
Rat Blood ◽  
Histamine Receptor Antagonists

scholarly journals Inhibition of cholinergic interneurons potentiates corticostriatal transmission in D1 receptor-expressing medium-sized spiny neurons and restores motor learning in parkinsonian condition

2021 ◽  
Author(s):  
Gwenaelle Laverne ◽  
Jonathan Pesce ◽  
Ana Reynders ◽  
Christophe Melon ◽  
Lydia Kerkerian-Le Goff ◽  
...  
Keyword(s):  
Motor Learning ◽  
Long Term Potentiation ◽  
D1 Receptor ◽  
Skill Learning ◽  
D1 Receptors ◽  
Projection Neurons ◽  
Cholinergic Interneurons ◽  
Term Potentiation ◽  
The Impact

Striatal cholinergic interneurons (CINs) respond to salient or reward prediction-related stimuli after conditioning with brief pauses in their activity, implicating them in learning and action selection. This pause is lost in animal models of Parkinson′s disease. How this signal regulates the functioning of the striatum remains an open question. To address this issue, we examined the impact of CIN firing inhibition on glutamatergic transmission between the cortex and the medium-sized spiny projection neurons expressing dopamine D1 receptors (D1 MSNs). Brief interruption of CIN activity had no effect in control condition whereas it increased glutamatergic responses in D1 MSNs after nigrostriatal dopamine denervation. This potentiation was dependent upon M4 muscarinic receptor and protein kinase A. Decreasing CIN firing by opto/chemogenetic strategies in vivo rescued long-term potentiation in some MSNs and alleviated motor learning deficits in parkinsonian mice. Taken together, our findings demonstrate that the control exerted by CINs on corticostriatal transmission and striatal-dependent motor-skill learning depends on the integrity of dopaminergic inputs.

scholarly journals Investigation of proteins important for microcirculation using in vivo microdialysis after glucose provocation: a proteomic study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexandra Högstedt ◽  
Simon Farnebo ◽  
Erik Tesselaar ◽  
Bijar Ghafouri
Keyword(s):  
Healthy Subjects ◽  
In Vivo Microdialysis ◽  
Vascular Effects ◽  
Microvascular Changes ◽  
Before And After ◽  
Proteomic Study ◽  
Time Periods ◽  
Tissue Compartments ◽  
Different Tissues

AbstractInsulin has metabolic and vascular effects in the human body. What mechanisms that orchestrate the effects in the microcirculation, and how the responds differ in different tissues, is however not fully understood. It is therefore of interest to search for markers in microdialysate that may be related to the microcirculation. This study aims to identify proteins related to microvascular changes in different tissue compartments after glucose provocation using in vivo microdialysis. Microdialysis was conducted in three different tissue compartments (intracutaneous, subcutaneous and intravenous) from healthy subjects. Microdialysate was collected during three time periods; recovery after catheter insertion, baseline and glucose provocation, and analyzed using proteomics. Altogether, 126 proteins were detected. Multivariate data analysis showed that the differences in protein expression levels during the three time periods, including comparison before and after glucose provocation, were most pronounced in the intracutaneous and subcutaneous compartments. Four proteins with vascular effects were identified (angiotensinogen, kininogen-1, alpha-2-HS-glycoprotein and hemoglobin subunit beta), all upregulated after glucose provocation compared to baseline in all three compartments. Glucose provocation is known to cause insulin-induced vasodilation through the nitric oxide pathway, and this study indicates that this is facilitated through the interactions of the RAS (angiotensinogen) and kallikrein-kinin (kininogen-1) systems.

Effect of bupropion on hippocampal neurotransmitters and on peripheral hormonal concentrations in the rat

2003 ◽  
Vol 95 (2) ◽  
pp. 652-656 ◽  
Author(s):  
M. F. Piacentini ◽  
R. Clinckers ◽  
R. Meeusen ◽  
S. Sarre ◽  
G. Ebinger ◽  
...  
Keyword(s):  
Significant Variation ◽  
Dopaminergic System ◽  
In Vivo Microdialysis ◽  
Sampling Time ◽  
Microdialysis Probe ◽  
Blood Samples ◽  
Before And After ◽  
Freely Moving ◽  
Vena Femoralis

The purpose of the present study was to administer an acute dose of the dual dopamine norepinephrine reuptake blocker bupropion in freely moving rats and to monitor the extracellular neurotransmitter concentrations in the hippocampus via in vivo microdialysis and the peripheral hormonal concentrations via catheterization. A microdialysis probe was inserted in the hippocampus, and samples for serotonin, dopamine, and norepinephrine were collected every 20 min before and after the injection of 17 mg/kg of bupropion, for a total sampling time of 180 min. A catheter was placed in the vena femoralis of the second group of rats, and blood samples were collected before and after bupropion injection for quantification of growth hormone, prolactin, corticosterone, adrenocorticotropin hormone, and β-endorphins. All neurotransmitter levels (dopamine, norepinephrine, and serotonin) significantly increased after bupropion injection. This was accompanied by a significant decrease in prolactin concentrations, whereas the other hormones showed no statistically significant variation. It can, therefore, be concluded that, although bupropion has dual reuptake proprieties, the observed effects both at the central and at the peripheral level seem to be ruled by the dopaminergic system.

Refining deep brain stimulation to emulate optogenetic treatment of synaptic pathology

Science ◽  
2015 ◽  
Vol 347 (6222) ◽  
pp. 659-664 ◽  
Author(s):  
Meaghan Creed ◽  
Vincent Jean Pascoli ◽  
Christian Lüscher
Keyword(s):  
Deep Brain Stimulation ◽  
Adaptive Behavior ◽  
Brain Stimulation ◽  
Metabotropic Glutamate Receptors ◽  
Behavioral Sensitization ◽  
Low Frequency ◽  
D1 Receptor ◽  
D1 Receptors ◽  
Deep Brain

Circuit remodeling driven by pathological forms of synaptic plasticity underlies several psychiatric diseases, including addiction. Deep brain stimulation (DBS) has been applied to treat a number of neurological and psychiatric conditions, although its effects are transient and mediated by largely unknown mechanisms. Recently, optogenetic protocols that restore normal transmission at identified synapses in mice have provided proof of the idea that cocaine-adaptive behavior can be reversed in vivo. The most efficient protocol relies on the activation of metabotropic glutamate receptors, mGluRs, which depotentiates excitatory synaptic inputs onto dopamine D1 receptor medium-sized spiny neurons and normalizes drug-adaptive behavior. We discovered that acute low-frequency DBS, refined by selective blockade of dopamine D1 receptors, mimics optogenetic mGluR-dependent normalization of synaptic transmission. Consequently, there was a long-lasting abolishment of behavioral sensitization.

scholarly journals Characterization of in vivo Pharmacokinetic Properties of the Dopamine D1 Receptor Agonist DAR-0100A in Nonhuman Primates Using PET with [11C] NNC112 and [11C] Raclopride

2010 ◽  
Vol 31 (1) ◽  
pp. 293-304 ◽  
Author(s):  
Mark Slifstein ◽  
Raymond F Suckow ◽  
Jonathan A Javitch ◽  
Thomas Cooper ◽  
Jeffrey Lieberman ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
D1 Receptor ◽  
D1 Receptors ◽  
Detectable Effect ◽  
Positron Emission ◽  
Pharmacokinetic Properties ◽  
D1 Agonist ◽  
Different Doses

DAR-0100A, the active enantiomer of dihydrexidine, is a potent dopamine D1 agonist under investigation for treatment of cognitive impairment and negative symptoms of schizophrenia. We measured the dose–occupancy relationship for DAR-0100A at D1 receptors using positron emission tomography (PET) imaging in baboons with [11C] NNC112 and its binding to D2 with [11C] raclopride. Two baboons were scanned with [11C] NNC112 at baseline and after three different doses of DAR-0100A. Two baboons were scanned with [11C] raclopride at baseline and after one dose of DAR-0100A. Occupancy (ΔBPND) was computed in the striatum and cortex. A clear relationship was observed between plasma concentration of DAR-0100A and ΔBPND. ΔBPND was larger in the striatum than in the cortex, consistent with reports showing that 25% of [11C] NNC112 BPND in the cortex is attributed to 5-HT2A. Plasma EC50 estimates ranged from 150 to 550 ng/mL according to the constraints on the model. There was no detectable effect of DAR-0100A on [11C] raclopride BPND. These data suggest that at doses likely to be administered to patients, occupancy will not be detectable with [11C] NNC112 PET and binding of DAR-0100A to D2 will be negligible. This is the first demonstration with PET of a significant occupancy by a full D1 agonist in vivo.

Investigation of the SSRI augmentation properties of 5-HT2 receptor antagonists using in vivo microdialysis

2006 ◽  
Vol 50 (6) ◽  
pp. 726-732 ◽  
Author(s):  
Laura J. Boothman ◽  
Stephen N. Mitchell ◽  
Trevor Sharp
Keyword(s):  
In Vivo Microdialysis ◽  
Receptor Antagonists

Radiolabeled r-Hirudin as a Measure of Thrombin Activity at, or within, the Rabbit Aorta Wall In Vitro and In Vivo

1994 ◽  
Vol 71 (04) ◽  
pp. 499-506 ◽  
Author(s):  
Mark W C Hatton ◽  
Bonnie Ross-Ouellet
Keyword(s):  
Rabbit Aorta ◽  
Balloon Injury ◽  
Recombinant Hirudin ◽  
Aorta Wall ◽  
Thrombin Activity ◽  
Before And After ◽  
The Matrix

SummaryThe behavior of 125I-labeled recombinant hirudin towards the uninjured and de-endothelialized rabbit aorta wall has been studied in vitro and in vivo to determine its usefulness as an indicator of thrombin activity associated with the aorta wall. Thrombin adsorbed to either sulfopropyl-Sephadex or heparin-Sepharose bound >95% of 125I-r-hirudin and the complex remained bound to the matrix. Binding of 125I-r-hirudin to the exposed aorta subendothelium (intima-media) in vitro was increased substantially if the tissue was pre-treated with thrombin; the quantity of l25I-r-hirudin bound to the de-endothelialized intima-media (i.e. balloon-injured in vitro) correlated positively with the quantity of bound 131I-thrombin (p <0.01). Aortas balloon-injured in vivo were measured for thrombin release from, and binding of 125I-r-hirudin to, the de-endothelialized intimal surface in vitro; 125I-r-hirudin binding correlated with the amount of active thrombin released (p <0.001). Uptake of 125I-r-hirudin by the aorta wall in vivo was proportional to the uptake of 131I-fibrinogen (as an indicator of thrombin activity) before and after balloon injury. After 30 min in the circulation, specific 125I-r-hirudin binding to the uninjured and de-endo- thelialized (at 1.5 h after injury) aorta wall was equivalent to 3.4 (± 2.5) and 25.6 (±18.1) fmol of thrombin/cm2 of intima-media, respectively. Possibly, only hirudin-accessible, glycosaminoglycan-bound thrombin is measured in this way.

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