scholarly journals Region-specific and dose-specific effects of chronic haloperidol exposure on [3H]-Flumazenil and [3H]-Ro15-4513 GABAA receptor binding sites in the rat brain

2019 ◽  
Author(s):  
Alba Peris-Yague ◽  
Amanda Kiemes ◽  
Diana Cash ◽  
Marie-Caroline Cotel ◽  
Nisha Singh ◽  
...  
Keyword(s):  
Rat Brain ◽  
Drug Exposure ◽  
Dorsal Hippocampus ◽  
Specific Binding ◽  
Receptor Autoradiography ◽  
Post Mortem ◽  
Sprague Dawley ◽  
Quantitative Receptor Autoradiography ◽  
Chronic Haloperidol

AbstractPost-mortem studies suggest that schizophrenia is associated with abnormal expression of specific GABAA receptor (GABAAR) α subunits, including α5GABAAR. Positron emission tomography (PET) measures of GABAAR availability in schizophrenia, however, have not revealed consistent alterations in vivo. Animal studies using the GABAAR agonist [3H]-muscimol provide evidence that antipsychotic drugs influence GABAAR availability, in a region-specific manner, suggesting a potential confounding effect of these drugs. No such data, however, are available for more recently developed subunit-selective GABAAR radioligands. To address this, we therefore combined a rat model of clinically relevant antipsychotic drug exposure with quantitative receptor autoradiography. Haloperidol (0.5 and 2 mg/kg/day) or drug vehicle were administered continuously to adult male Sprague-Dawley rats via osmotic mini-pumps for 28 days. Quantitative receptor autoradiography was then performed post-mortem using the GABAAR subunit-selective radioligand [3H]-Ro15-4513 and the non-subunit selective radioligand [3H]-flumazenil. Chronic haloperidol exposure increased [3H]-Ro15-4513 binding in the CA1 sub-field of the rat dorsal hippocampus (p<0.01; q<0.01; d = +1.3), which was not dose-dependent. [3H]-flumazenil binding also increased in most rat brain regions (p<0.05; main effect of treatment), irrespective of the haloperidol dose. These data confirm previous findings that chronic haloperidol exposure influences the specific binding of non-subtype selective GABAAR radioligands and is the first to demonstrate a potential effect of haloperidol on the binding of a α1/5GABAAR-selective radioligand. Although caution should be exerted when extrapolating results from animals to patients, our data support a view that exposure to antipsychotics may be a confounding factor in PET studies of GABAAR in the context of schizophrenia.

Androgens augment proximal tubule transport

2004 ◽  
Vol 287 (3) ◽  
pp. F452-F459 ◽  
Author(s):  
Albert Quan ◽  
Sumana Chakravarty ◽  
Jian-Kang Chen ◽  
Jian-Chun Chen ◽  
Samer Loleh ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Specific Binding ◽  
Extracellular Volume ◽  
Renin Angiotensin System ◽  
Angiotensin Receptors ◽  
Sprague Dawley ◽  
Angiotensin System ◽  
Renin Angiotensin

The proximal tubule contains an autonomous renin-angiotensin system that regulates transport independently of circulating angiotensin II. Androgens are known to increase expression of angiotensinogen, but the effect of androgens on proximal tubule transport is unknown. In this in vivo microperfusion study, we examined the effect of androgens on proximal tubule transport. The volume reabsorptive rate in Sprague-Dawley rats given dihydrotestosterone (DHT) injections was significantly higher than in control rats given vehicle injections (4.57 ± 0.31 vs. 3.31 ± 0.23 nl·min−1·mm−1, P < 0.01). Luminally perfusing with either enalaprilat (10−4 M) to inhibit production of angiotensin II or losartan (10−8 M) to block the angiotensin receptor decreased the proximal tubule volume reabsorptive rate in DHT-treated rats to a significantly greater degree than in control vehicle-injected rats. The renal expression of angiotensinogen was shown to be higher in the DHT-treated animals, using Northern blot analysis. The expression of angiotensin receptors, determined by specific binding of angiotensin II, was not different in the two groups of animals. Brush-border membrane protein abundance of the Na/H exchanger, a membrane transport protein under angiotensin II regulation, was also higher in DHT-treated rats vs. control rats. Rats that received DHT had higher blood pressures than the control rats but had no change in their glomerular filtration rate. In addition, serum angiotensin II levels were lower in DHT-treated vs. control rats. These results suggest that androgens may directly upregulate the proximal tubule renin-angiotensin system, increase the volume reabsorptive rate, and thereby increase extracellular volume and blood pressure and secondarily decrease serum angiotensin II levels.

Comparative studies on tryptophan binding to hepatic nuclear envelopes in Sprague-Dawley and Lewis rats

1994 ◽  
Vol 267 (2) ◽  
pp. R502-R507 ◽  
Author(s):  
H. Sidransky ◽  
E. Verney
Keyword(s):  
Inflammatory Diseases ◽  
Specific Binding ◽  
Quantitative Difference ◽  
Sprague Dawley ◽  
Lewis Rats ◽  
Sprague Dawley Rats ◽  
Nuclear Rna ◽  
Eosinophilia Myalgia Syndrome

Since Lewis rats are susceptible to many inflammatory diseases and have been used in an experimental model of the eosinophilia-myalgia syndrome, we investigated whether Lewis rats would respond to L-tryptophan as have Sprague-Dawley rats reported earlier. In this comparative study using females of both strains, we observed a decrease in the affinity of in vitro L-tryptophan binding to hepatic nuclei and nuclear envelopes of Lewis rats compared with Sprague-Dawley rats. However, in vivo stimulatory effects of administering L-tryptophan on hepatic polyribosomal aggregation, protein synthesis, and nuclear RNA release were similar in both strains. In vitro [3H]tryptophan binding to hepatic nuclear envelopes, using L-tryptophan implicated in cases of the eosinophilia-myalgia syndrome, revealed less specific binding than when using nonimplicated L-tryptophan in both strains. The possible significance of the quantitative difference in the binding affinity of L-tryptophan to hepatic nuclei of Lewis rats compared with those of Sprague-Dawley rats is as yet undetermined.

Effect of Hyperbaric Oxygen Treatment on Nitric Oxide and Oxygen Free Radicals in Rat Brain

2000 ◽  
Vol 83 (4) ◽  
pp. 2022-2029 ◽  
Author(s):  
Ikram M. Elayan ◽  
Milton J. Axley ◽  
Paruchuri V. Prasad ◽  
Stephen T. Ahlers ◽  
Charles R. Auker
Keyword(s):  
Nitric Oxide ◽  
Free Radicals ◽  
Rat Brain ◽  
Hyperbaric Oxygen ◽  
High Pressures ◽  
Oxygen Free Radicals ◽  
In Vivo Microdialysis ◽  
Sprague Dawley ◽  
Fourfold Increase

Oxygen (O2) at high pressures acts as a neurotoxic agent leading to convulsions. The mechanism of this neurotoxicity is not known; however, oxygen free radicals and nitric oxide (NO) have been suggested as contributors. This study was designed to follow the formation of oxygen free radicals and NO in the rat brain under hyperbaric oxygen (HBO) conditions using in vivo microdialysis. Male Sprague-Dawley rats were exposed to 100% O2 at a pressure of 3 atm absolute for 2 h. The formation of 2,3-dihydroxybenzoic acid (2,3-DHBA) as a result of perfusing sodium salicylate was followed as an indicator for the formation of hydroxyl radicals. 2,3-DHBA levels in hippocampal and striatal dialysates of animals exposed to HBO conditions were not significantly different from controls. However, rats treated under the same conditions showed a six- and fourfold increase in nitrite/nitrate, break down products of NO decomposition, in hippocampal and striatal dialysates, respectively. This increase was completely blocked by the nitric oxide synthase (NOS) inhibitor l-nitroarginine methyl ester (l-NAME). Using neuronal NOS, we determined the NOS O2 K m to be 158 ± 28 (SD) mmHg, a value which suggests that production of NO by NOS would increase approximately four- to fivefold under hyperbaric O2 conditions, closely matching the measured increase in vivo. The increase in NO levels may be partially responsible for some of the detrimental effects of HBO conditions.

In Vitro and in Vivo Investigations of the Specific Binding of Substance P-γ-Cyclodextrin Adducts to Rat Brain Nk1 Receptors

1999 ◽  
pp. 403-406
Author(s):  
C. Pean ◽  
J. Fischer ◽  
S. Doly ◽  
A. Wijkhuisene ◽  
F. Djedaini-Pilard ◽  
...  
Keyword(s):  
Substance P ◽  
Rat Brain ◽  
Specific Binding ◽  
Nk1 Receptors

Long-term reproducibility of in vivo measures of specific binding of radioligands in rat brain

2004 ◽  
Vol 31 (5) ◽  
pp. 591-595 ◽  
Author(s):  
Michael R Kilbourn
Keyword(s):  
Rat Brain ◽  
Specific Binding

Identification and characterization of binding sites for human urotensin-II in Sprague–Dawley rat renal medulla using quantitative receptor autoradiography

Peptides ◽  
2006 ◽  
Vol 27 (6) ◽  
pp. 1532-1537 ◽  
Author(s):  
Jyoti Disa ◽  
Latitia E. Floyd ◽  
Richard M. Edwards ◽  
Stephen A. Douglas ◽  
Nambi V. Aiyar
Keyword(s):  
Binding Sites ◽  
Renal Medulla ◽  
Receptor Autoradiography ◽  
Urotensin Ii ◽  
Sprague Dawley ◽  
Quantitative Receptor Autoradiography ◽  
Sprague Dawley Rat ◽  
Identification And Characterization

Distribution of [3H]kainic acid and binding sites in the rat brain: in vivo and in vitro receptor autoradiography

1986 ◽  
Vol 70 (3) ◽  
pp. 301-307 ◽  
Author(s):  
Smita Patel ◽  
Brian S. Meldrum ◽  
James F. Collins
Keyword(s):  
Rat Brain ◽  
Kainic Acid ◽  
Binding Sites ◽  
Receptor Autoradiography ◽  
In Vitro Receptor Autoradiography

scholarly journals Quantification of [11C]yohimbine Binding to α2 Adrenoceptors in Rat Brain in vivo

2015 ◽  
Vol 35 (3) ◽  
pp. 501-511 ◽  
Author(s):  
Jenny-Ann Phan ◽  
Anne M Landau ◽  
Dean F Wong ◽  
Steen Jakobsen ◽  
Adjmal Nahimi ◽  
...  
Keyword(s):  
Rat Brain ◽  
Volume Of Distribution ◽  
Sprague Dawley ◽  
Logan Plot ◽  
Positron Emission ◽  
Amphetamine Administration ◽  
Sprague Dawley Rats ◽  
Extracellular Level ◽  
Arterial Plasma

We quantified the binding potentials ( BPND) of [11C]yohimbine binding in rat brain to alpha-2 adrenoceptors to evaluate [11C]yohimbine as an in vivo marker of noradrenergic neurotransmission and to examine its sensitivity to the level of noradrenaline. Dual [11C]yohimbine dynamic positron emission tomography (PET) recordings were applied to five Sprague Dawley rats at baseline, followed by acute amphetamine administration (2 mg/kg) to induce elevation of the endogenous level of noradrenaline. The volume of distribution ( VT) of [11C]yohimbine was obtained using Logan plot with arterial plasma input. Because alpha-2 adrenoceptors are distributed throughout the brain, the estimation of the BPND is complicated by the absence of an anatomic region of no displaceable binding. We used the Inhibition plot to acquire the reference volume, VND, from which we calculated the BPND. Acute pharmacological challenge with amphetamine induced a significant decline of [11C]yohimbine BPND of ∼38% in all volumes of interest. The BPND was greatest in the thalamus and striatum, followed in descending order by, frontal cortex, pons, and cerebellum. The experimental data demonstrate that [11C]yohimbine binding is sensitive to a challenge known to increase the extracellular level of noradrenaline, which can benefit future PET investigations of pathologic conditions related to disrupted noradrenergic neurotransmission.

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