Administration of the glial cell modulator, minocycline, in the nucleus accumbens attenuated the maintenance and reinstatement of morphine-seeking behavior

2016 ◽  
Vol 94 (3) ◽  
pp. 257-264 ◽  
Author(s):  
Reza Arezoomandan ◽  
Abbas Haghparast
Keyword(s):  
Drug Abuse ◽  
Nucleus Accumbens ◽  
Therapeutic Agent ◽  
Extinction Period ◽  
Priming Dose ◽  
Morphine Treatment ◽  
Seeking Behavior ◽  
New Evidence ◽  
Clinical Problems ◽  
Promising Therapeutic Agent

Relapse to drug use is one of the most difficult clinical problems in treating addiction. Glial activation has been linked with the drug abuse, and the glia modulators such as minocycline can modulate the drug abuse effects. The aim of the present study was to determine whether minocycline could attenuate the maintenance and reinstatement of morphine. Conditioned place preference (CPP) was induced by subcutaneous injection of morphine (5 mg/kg) for 3 days. Following the acquisition of the CPP, the rats were given daily bilateral intra-NAc injections of either minocycline (1, 5, and 10 μg/0.5 μL) or saline (0.5 μL). The animals were tested for conditioning score 60 min after each injection. To induce the reinstatement, a priming dose of morphine (1 mg/kg) was injected 1 day after the final extinction day. The morphine-induced CPP lasted for 7 days after cessation of morphine treatment. Our data revealed that a priming dose of morphine could reinstate the extinguished morphine-induced CPP. Daily intra-accumbal injection of minocycline during the extinction period blocked the maintenance of morphine CPP and also attenuated the priming-induced reinstatement. Our findings indicated that minocycline could facilitate the extinction and attenuate the reinstatement of morphine. These results provided new evidence that minocycline might be considered as a promising therapeutic agent for the treatment of several symptoms associated with morphine abuse.

scholarly journals Assessing the Effect of Diazepam on Methamphetamine-induced Seeking Behavior in Rats

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Kamaledin Alaedini ◽  
Maryam Zahmatkesh ◽  
Esmaeel Riahi ◽  
Elaheh Karimi ◽  
Maryam Farahmandfar
Keyword(s):  
Single Dose ◽  
Similar Process ◽  
Control Group ◽  
Extinction Period ◽  
Withdrawal Period ◽  
Priming Dose ◽  
Priming Phase ◽  
Seeking Behavior ◽  
Male Wistar Rats ◽  
Group 2

Background: Relapse is a common problem in substance-use disorders. Accumulating evidence has shown that diazepam can reduce the abuse potential of some drugs. Objectives: We investigated the effects of diazepam during and after the withdrawal period on the reinstatement of conditioned place preference (CPP) induced by a single dose of methamphetamine in male Wistar rats. Methods: Three groups of rats were trained to acquire methamphetamine CPP. The rats in the control group received, respectively, saline and methamphetamine (1 mg/kg, daily, ip) in the extinction and priming phases. Two other groups (one and two) had a similar process, but the rats in group one received diazepam (3 mg/kg, daily, ip) in the extinction phase and those in group 2 received a single dose of diazepam just before the priming phase. The CPP was checked daily during all processes. Results: We showed that a 3-day period injection of methamphetamine (1 mg/kg) resulted in a positive conditioning score on the first day after conditioning. Also, 3 mg/kg of diazepam daily in the extinction period shortened the withdrawal period for one day and extinction happened on the 9th and 10th days. Diazepam also reduced the conditioning score at the reinstatement phase (P < 0.01). Furthermore, diazepam injection (3 mg/kg) before the methamphetamine priming dose did not have any significant effect on the reinstatement of drug-seeking. Conclusions: This study demonstrated that administration of diazepam during the extinction period was associated with reduced maintenance and reinstatement of methamphetamine-induced CPP, while the single dose of diazepam could not prevent the reinstatement of methamphetamine.

Dopaminylation in Psychostimulant use Disorder Protects Against Psychostimulant Seeking Behavior by Normalizing Nucleus Accumbens (NAc) Dopamine Expression

2021 ◽  
Vol 09 ◽  
Author(s):  
Kenneth Blum ◽  
Mark S Gold ◽  
Jean L. Cadet ◽  
David Baron ◽  
Abdalla Bowirrat ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Histone H3 ◽  
D2 Receptor ◽  
Reward Processing ◽  
Allelic Polymorphism ◽  
Cocaine Withdrawal ◽  
Src Signaling ◽  
Chronic Cocaine ◽  
Cocaine Seeking ◽  
Seeking Behavior

Background: Repeated cocaine administration changes histone acetylation and methylation on Lys residues and Deoxyribonucleic acid (DNA) within the nucleus accumbens (NAc). Recently Nestler’s group explored histone Arg (R) methylation in reward processing models. Damez-Werno et al. (2016) reported that during investigator and selfadministration experiments, the histone mark protein-R-methyltransferase-6 (PRMT6) and asymmetric dimethylation of R2 on histone H3 (H3R2me2a) decreased in the rodent and cocaine-dependent human NAc. Overexpression of PRMT6 in D2-MSNs in all NAc neurons increased cocaine seeking, whereas PRMT6 overexpression in D1-MSNs protects against cocaine-seeking. Hypothesis: Hypothesizing that dopaminylation (H3R2me2a binding) occurs in psychostimulant use disorder (PSU), and the binding inhibitor Srcin1, like the major DRD2 A2 allelic polymorphism, protects against psychostimulant seeking behavior by normalizing nucleus accumbens (NAc) dopamine expression. Discussion: Numerous publications confirmed the association between the DRD2 Taq A1 allele (30-40 lower D2 receptor numbers) and severe cocaine dependence. Lepack et al. (2020) found that acute cocaine increases dopamine in NAc synapses, results in histone H3 glutamine 5 dopaminylation (H3Q5dop), and consequent inhibition of D2 expression. The inhibition increases with chronic cocaine use and accompanies cocaine withdrawal. They also found that the Src kinase sig-naling inhibitor 1 (Srcin1 or p140CAP) during cocaine withdrawal reduced H3R2me2a binding. Consequently, this inhibited dopaminylation induced a “homeostatic brake.” Conclusion: The decrease in Src signaling in NAc D2-MSNs, like the DRD2 Taq A2 allele, a well-known genetic mechanism protective against SUD normalized nucleus accumbens (NAc) dopamine expression and decreased cocaine reward and motivation to self-administer cocaine. The Srcin1 may be an important therapeutic target.

scholarly journals The Adenosine A2A Receptor Activation in Nucleus Accumbens Suppress Cue-Induced Reinstatement of Propofol Self-administration in Rats

2021 ◽  
Author(s):  
Zhanglei Dong ◽  
Bingwu Huang ◽  
Chenchen Jiang ◽  
Jiangfan Chen ◽  
Han Lin ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
D2 Receptor ◽  
Fixed Ratio ◽  
Receptor Activation ◽  
Addictive Behaviors ◽  
Self Administration ◽  
A2a Receptors ◽  
Mediated Effects ◽  
Seeking Behavior ◽  
Adenosine A2a

AbstractPropofol has shown strong addictive properties in rats and humans. Adenosine A2A receptors (A2AR) in the nucleus accumbens (NAc) modulate dopamine signal and addictive behaviors such as cocaine- and amphetamine-induced self-administration. However, whether A2AR can modulate propofol addiction remains unknown. AAV-shA2AR was intra-NAc injected 3 weeks before the propofol self-administration training to test the impacts of NAc A2AR on establishing the self-administration model with fixed ratio 1 (FR1) schedule. Thereafter, the rats were withdrawal from propofol for 14 days and tested cue-induced reinstatement of propofol seeking behavior on day 15. The propofol withdrawal rats received one of the doses of CGS21680 (A2AR agonist, 2.5–10.0 ng/site), MSX-3 (A2AR antagonist, 5.0–20.0 μg/site) or eticlopride (D2 receptor (D2R) antagonist, 0.75–3.0 μg/site) or vehicle via intra-NAc injection before relapse behavior test. The numbers of active and inactive nose-poke response were recorded. Focal knockdown A2AR by shA2AR did not affect the acquisition of propofol self-administration behavior, but enhance cue-induced reinstatement of propofol self-administration compared with the AAV-shCTRLgroup. Pharmacological activation of the A2AR by CGS21680 (≥ 5.0 ng/site) attenuated cue-induced reinstatement of propofol self-administration behavior. Similarly, pharmacological blockade of D2R by eticlopride (0.75–3.0 μg/site) attenuated propofol seeking behavior. These effects were reversed by the administration of MSX-3 (5.0–20.0 μg/site). The A2AR- and D2R-mediated effects on propofol relapse were not confounded by the learning process, and motor activity as the sucrose self-administration and locomotor activity were not affected by all the treatments. This study provides genetic and pharmacological evidence that NAc A2AR activation suppresses cue-induced propofol relapse in rats, possibly by interacting with D2R.

scholarly journals Therapeutic Management of a Substantial Pelvic Aneurysmatic Bone Cyst Including the Off-Label Use of Denosumab in a 35-Year-Old Female Patient

2017 ◽  
Vol 2017 ◽  
pp. 1-5
Author(s):  
D. Ntalos ◽  
M. Priemel ◽  
C. Schlickewei ◽  
D. M. Thiesen ◽  
J. M. Rueger ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Female Patient ◽  
Therapeutic Agent ◽  
Surgical Intervention ◽  
Case Reports ◽  
Bone Cyst ◽  
Off Label Use ◽  
Aneurysmal Bone Cysts ◽  
Promising Therapeutic Agent

Aneurysmal bone cysts (ABC) are benign bone tumors, which are highly vascularized. The main course of treatment is curettage followed by bone grafting or cement insertion. Still recurrence remains a main problem for patients. Denosumab is a monoclonal antibody, which acts as an inhibitor of the RANK/RANKL pathway, diminishing bone turnover. Recent case reports have shown that Denosumab can be a promising therapeutic agent for people suffering from therapy-resistant ABC. We report the case of a 35-year-old female patient presenting with a pronounced ABC of the pelvis. Since the tumor was inoperable, Denosumab was administered, leading to a significant shrinkage of the lesion, which allowed surgical intervention. Upon recurrence, Denosumab was restarted putting the patient once more into remission. Follow-up was four years overall with a clinical and radiological stable disease for fifteen months after final discontinuation of the monoclonal antibody. Therefore, our case further underlines the potential of Denosumab in the treatment of ABC.

scholarly journals Author Correction: A VCP modulator, KUS121, as a promising therapeutic agent for post-traumatic osteoarthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Motoo Saito ◽  
Kohei Nishitani ◽  
Hanako O. Ikeda ◽  
Shigeo Yoshida ◽  
Sachiko Iwai ◽  
...  
Keyword(s):  
Therapeutic Agent ◽  
Post Traumatic ◽  
Promising Therapeutic Agent

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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