scholarly journals Cell-type specific expression and behavioral impact of galanin and GalR1 in the locus coeruleus during opioid withdrawal

2021 ◽  
Author(s):  
Stephanie L. Foster ◽  
Ewa Galaj ◽  
Saumya L. Karne ◽  
Sergi Ferré ◽  
David Weinshenker
Keyword(s):  
Locus Coeruleus ◽  
Mrna Expression ◽  
Receptor Agonist ◽  
Opioid Withdrawal ◽  
Withdrawal Symptoms ◽  
Galanin Receptor ◽  
Chronic Morphine ◽  
Specific Expression ◽  
General Role ◽  
Precipitated Withdrawal

ABSTRACTThe neuropeptide galanin is reported to attenuate opioid withdrawal symptoms, potentially by reducing neuronal hyperactivity in the noradrenergic locus coeruleus (LC) via galanin receptor 1 (GalR1). We evaluated this mechanism by using RNAscope in situ hybridization to characterize GalR1 mRNA distribution in the dorsal pons and to compare galanin and GalR1 mRNA expression in tyrosine hydroxylase-positive (TH+) LC cells at baseline and following chronic morphine or precipitated withdrawal. We then used genetically altered mouse lines and pharmacology to test whether noradrenergic galanin (NE-Gal) modulates withdrawal symptoms. RNAscope revealed that, while GalR1 signal was abundant in the dorsal pons, 80.7% of the signal was attributable to TH-neurons outside the LC. Galanin and TH mRNA were abundant in LC cells at baseline and were further increased by withdrawal, whereas low basal GalR1 mRNA expression was unaltered by chronic morphine or withdrawal. Naloxone-precipitated withdrawal symptoms in mice lacking NE-Gal (GalcKO-Dbh) were largely similar to WT littermates, indicating that loss of NE-Gal does not exacerbate withdrawal. Complimentary experiments using NE-Gal overexpressor mice (NE-Gal OX) and systemic administration of the galanin receptor agonist galnon revealed that increasing galanin signaling also failed to alter behavioral withdrawal, while suppressing noradrenergic transmission with the alpha-2 adrenergic receptor agonist clonidine attenuated multiple symptoms. These results indicate that galanin does not acutely attenuate precipitated opioid withdrawal via an LC-specific mechanism, which has important implications for the general role of galanin in regulation of somatic and affective opioid responses and LC activity.

Attenuation of morphine withdrawal signs by a D1 receptor agonist in the locus coeruleus of rats

Neuroreport ◽  
2005 ◽  
Vol 16 (15) ◽  
pp. 1683-1686 ◽  
Author(s):  
Iraj Mirzaii Dizgah ◽  
Seyed Morteza Karimian ◽  
Mohammad Reza Zarrindast ◽  
Hamid Sohanaki
Keyword(s):  
Locus Coeruleus ◽  
Receptor Agonist ◽  
D1 Receptor ◽  
Morphine Withdrawal ◽  
Withdrawal Signs ◽  
Morphine Withdrawal Signs

scholarly journals A 5-Methylcytosine Site of Growth Differentiation Factor 9 (GDF9) Gene Affects Its Tissue-Specific Expression in Sheep

Animals ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 200
Author(s):  
Zhangyuan Pan ◽  
Xiangyu Wang ◽  
Ran Di ◽  
Qiuyue Liu ◽  
Wenping Hu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Methylation Level ◽  
Cpg Island ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Directed Mutation ◽  
Differentiation Factor ◽  
Growth Differentiation Factor 9 ◽  
Basal Transcriptional Activity

Growth differentiation factor 9 (GDF9) plays an important role in the early folliculogenesis of sheep. This study investigated the mRNA expression of ovine GDF9 in different tissues by real-time PCR. GDF9 exhibits significantly higher levels of expression (p < 0.01) in the ovary, relative to other tissues, indicating that its expression is tissue specific. To explore the regulatory mechanism of this tissue-specific expression, the methylation level of one CpG island (−1453 to −1854) of GDF9 promoter in ovary and heart was determined. In this region (−1987 to −1750), only the mC-4 site was present in the Sp4 binding site showed differential methylation between the heart and ovary; with increased (p < 0.01) methylation being observed in the heart. Additionally, the methylation level was negatively correlated with GDF9 mRNA expression (R = −0.75, p = 0.012), indicating that the methylation of this site plays an important role in transcriptional regulation of GDF9. The methylation effect of the mC-4 site was confirmed by using dual-luciferase. Site-directed mutation (methylation) of mC-4 site significantly reduced (p < 0.05) basal transcriptional activity of GDF9 promoter in oocytes. These results imply that methylation of GDF9 promoter CpG island mC-4 site may affect the binding of the Sp4 transcription factor to the GDF9 promoter region in sheep, thereby regulating GDF9 expression and resulting in a tissue-specific expression.

scholarly journals Synthesis of galmic: A nonpeptide galanin receptor agonist

2004 ◽  
Vol 101 (48) ◽  
pp. 16727-16732 ◽  
Author(s):  
S. C. Ceide ◽  
L. Trembleau ◽  
G. Haberhauer ◽  
L. Somogyi ◽  
X. Lu ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Galanin Receptor

scholarly journals Carbon Nanotube Membranes for use in the Transdermal Treatment of Nicotine Addiction and Opioid Withdrawal Symptoms

2009 ◽  
Vol 3 ◽  
pp. SART.S1050
Author(s):  
Caroline L. Strasinger ◽  
Nicole N. Scheff ◽  
Ji Wu ◽  
Bruce J. Hinds ◽  
Audra L. Stinchcomb
Keyword(s):  
Drug Delivery ◽  
Carbon Nanotube ◽  
Opioid Withdrawal ◽  
Withdrawal Symptoms ◽  
Nanotube Membranes ◽  
Dosing Regimens ◽  
Carbon Nanotube Membranes ◽  
Variable Flux ◽  
Electrical Bias ◽  
Current Systems

Transdermal systems are attractive methods of drug administration specifically when treating patients for drug addiction. Current systems however are deficient in therapies that allow variable flux values of drug, such as nicotine for smoking cessation or complex dosing regimens using clonidine when treating opioid withdrawal symptoms. Through the use of functionalized carbon nanotube (CNT) membranes, drug delivery to the skin can be controlled by applying a small electrical bias to create a programmable drug delivery system. Clearly, a transdermal patch system that can be tailored to an individual's needs will increase patient compliance as well as provide much more efficient therapy. The purpose of this paper is to discuss the applicability of using carbon nanotube membranes in transdermal systems for treatment of drug abuse.

scholarly journals Developmental Expression of Mouse Erythrocyte Protein 4.2 mRNA: Evidence for Specific Expression in Erythroid Cells

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 695-705 ◽  
Author(s):  
Lingyun Zhu ◽  
Samir B. Kahwash ◽  
Long-Sheng Chang
Keyword(s):  
Mrna Expression ◽  
Fetal Liver ◽  
Late Gestation ◽  
Developmental Expression ◽  
Erythroid Cells ◽  
Mouse Development ◽  
Specific Expression ◽  
Protein 4.2 ◽  
Specific Regulation ◽  
In Erythroid Cells

Abstract Erythrocyte protein 4.2 (P4.2) is an important component of the erythrocyte membrane skeletal network with an undefined biologic function. Presently, very little is known about the expression of the P4.2 gene during mouse embryonic development and in adult animals. By using the Northern blot and in situ hybridization techniques, we have examined the spatial and temporal expression of the P4.2 gene during mouse development. We show that expression of the mouse P4.2 gene is temporally regulated during embryogenesis and that the P4.2 mRNA expression pattern coincides with the timing of erythropoietic activity in hematopoietic organs. P4.2 transcripts are first detected in embryos on day 7.5 of gestation and are localized exclusively in primitive erythroid cells of yolk sac origin. These erythroid cells remain to be the only source for P4.2 expression until the switch of the hematopoietic producing site to fetal liver. In mid- and late-gestation periods, P4.2 mRNA expression is restricted to the erythroid cells in fetal liver and to circulating erythrocytes. Around and after birth, the site for P4.2 expression is switched from liver to spleen and bone marrow, and P4.2 transcripts are only detected in cells of the erythroid lineage. These results provide the evidence for specific P4.2 expression in erythroid cells. In addition, the timing and pattern of expression of the P4.2 gene suggest the specific regulation of the P4.2 gene.

scholarly journals Lofexidine for acute opioid withdrawal: A clinical case series

2020 ◽  
Vol 10 (5) ◽  
pp. 259-263
Author(s):  
Mandy L. Renfro ◽  
Lindsey J. Loera ◽  
Carlos F. Tirado ◽  
Lucas G. Hill
Keyword(s):  
Addiction Treatment ◽  
Case Series ◽  
Retrospective Chart Review ◽  
The United States ◽  
Opioid Withdrawal ◽  
Withdrawal Symptoms ◽  
Total Daily Dose ◽  
Opioid Use ◽  
Management Protocol ◽  
Patient Reported

Abstract Introduction Maintaining abstinence through the opioid withdrawal period is a substantial barrier to treatment for patients with opioid use disorder. The alpha-2 agonist lofexidine has demonstrated efficacy and safety in clinical trials, but pragmatic studies describing its use in clinical practice are lacking. This case series describes the use of lofexidine for opioid withdrawal symptoms in an inpatient addiction treatment facility. Methods Seventeen patients receiving at least 1 dose of lofexidine during inpatient treatment for opioid withdrawal were included in this study. A retrospective chart review was conducted for clinical, subjective, and objective data. Adverse events, total daily dose, clinical opioid withdrawal scale (COWS) scores, vital signs, and reasons for early discontinuation of lofexidine are reported. Results Patients treated with lofexidine experienced mild withdrawal symptoms throughout treatment. Most patients (65%) experienced a decrease in their average daily COWS scores from intake to discharge. Two patients (12%) left treatment against medical advice, and 5 patients (29%) discontinued treatment prior to day 7 due to resolution of symptoms. Average daily blood pressure readings remained stable, and daily average heart rate decreased over time. Discussion Lofexidine can be successfully incorporated into a conventional withdrawal management protocol. The cost of lofexidine and its recent introduction to the market remain barriers to accessibility in the United States. Studies evaluating patient-reported outcomes as well as direct comparisons with other alpha-2 agonists are needed to inform optimal clinical use of lofexidine.

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