scholarly journals Pharmacological insights into the role of P2X4 receptors in behavioural regulation: lessons from ivermectin

2013 ◽  
Vol 16 (5) ◽  
pp. 1059-1070 ◽  
Author(s):  
Marco Bortolato ◽  
Megan M. Yardley ◽  
Sheraz Khoja ◽  
Sean C. Godar ◽  
Liana Asatryan ◽  
...  

Abstract Purinergic ionotropic P2X receptors are a family of cation-permeable channels that bind extracellular adenosine 5′-triphosphate. In particular, convergent lines of evidence have recently highlighted P2X4 receptors as a potentially critical target in the regulation of multiple nervous and behavioural functions, including pain, neuroendocrine regulation and hippocampal plasticity. Nevertheless, the role of the P2X4 receptor in behavioural organization remains poorly investigated. To study the effects of P2X4 activation, we tested the acute effects of its potent positive allosteric modulator ivermectin (IVM, 2.5–10 mg/kg i.p.) on a broad set of paradigms capturing complementary aspects of perceptual, emotional and cognitive regulation in mice. In a novel open field, IVM did not induce significant changes in locomotor activity, but increased the time spent in the peripheral zone. In contrast, IVM produced anxiolytic-like effects in the elevated plus maze and marble burying tasks, as well as depression-like behaviours in the tail-suspension and forced swim tests. The agent induced no significant behavioural changes in the conditioned place preference test and in the novel object recognition task. Finally, the drug induced a dose-dependent decrease in sensorimotor gating, as assessed by pre-pulse inhibition (PPI) of the acoustic startle reflex. In P2X4 knockout mice, the effects of IVM in the open field and elevated plus maze were similar to those observed in wild type mice; conversely, the drug significantly increased startle amplitude and failed to reduce PPI. Taken together, these results suggest that P2X4 receptors may play a role in the regulation of sensorimotor gating.

2013 ◽  
Vol 120 ◽  
pp. 130-135 ◽  
Author(s):  
Daniela Rebolledo-Solleiro ◽  
Minerva Crespo-Ramírez ◽  
Gabriel Roldán-Roldán ◽  
Marcia Hiriart ◽  
Miguel Pérez de la Mora

2002 ◽  
Vol 60 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Juan Carlos Martı́nez ◽  
Fernando Cardenas ◽  
Marisol Lamprea ◽  
Silvio Morato
Keyword(s):  

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Juan Francisco Rodríguez-Landa ◽  
Rosa Isela García-Ríos ◽  
Jonathan Cueto-Escobedo ◽  
Blandina Bernal-Morales ◽  
Carlos M. Contreras

Human amniotic fluid and a mixture of eight fatty acids (FAT-M) identified in this maternal fluid (C12:0, lauric acid, 0.9 μg%; C14:0, myristic acid, 6.9 μg%; C16:0, palmitic acid, 35.3 μg%; C16:1, palmitoleic acid, 16.4 μg%; C18:0, stearic acid, 8.5 μg%; C18:1cis, oleic acid, 18.4 μg%; C18:1trans, elaidic acid, 3.5 μg%; C18:2, linoleic acid, 10.1 μg%) produce anxiolytic-like effects that are comparable to diazepam in Wistar rats, suggesting the involvement ofγ-aminobutyric acid-A (GABAA) receptors, a possibility not yet explored. Wistar rats were subjected to the defensive burying test, elevated plus maze, and open field test. In different groups, threeGABAAreceptor antagonists were administered 30 min before FAT-M administration, including the competitive GABA binding antagonist bicuculline (1 mg/kg),GABAAbenzodiazepine antagonist flumazenil (5 mg/kg), and noncompetitiveGABAAchloride channel antagonist picrotoxin (1 mg/kg). The FAT-M exerted anxiolytic-like effects in the defensive burying test and elevated plus maze, without affecting locomotor activity in the open field test. TheGABAAantagonists alone did not produce significant changes in the behavioral tests. Picrotoxin but not bicuculline or flumazenil blocked the anxiolytic-like effect of the FAT-M. Based on the specific blocking action of picrotoxin on the effects of the FAT-M, we conclude that the FAT-M exerted its anxiolytic-like effects throughGABAAreceptor chloride channels.


2020 ◽  
Vol 1 (5) ◽  
pp. 12-23
Author(s):  
A.R. Abubakar ◽  
◽  
I.H. Sani ◽  
S. Malami ◽  
A.H. Yaro ◽  
...  

Background: Solanum aethiopicum (L.), family Solanaceae, is known as garden eggs. The fruit is used in the treatment of insomnia, diabetes and constipation. Objective: The aim of this study was to evaluate anxiolytic-like activity of fractions obtained from crude methanol extract of Solanum aethiopicum fruit. Method: Acute toxicity testing was conducted according to the OECD guidelines 420 via oral and intraperitoneal routes (ip). n-Hexane (HF), chloroform (CHF), ethyl-acetate (EAF), n-butanol (BF) and residual aqueous fraction (RAF) at doses of 25, 50 and 100 mg/kg ip were experimented using the open field, elevated plus maze, staircase, light dark box and hole-board tests. Results: Results: In open field test, there was statistically significant increase in frequency of central square entry by EAF 25mg/kg, 50mg/kg and 100mg/kg and RAF 25mg/kg, 50mg/kg and 100mg/kg all at p<0.05 compared to distilled water (D/W) group. Elevated plus maze test showed statistically significant increases in open arm entry and duration by CHF 25mg/kg, RAF 25mg/kg and 50mg/kg again at p<0.05. Also, in the staircase test, statistically significant decrease in frequency of rearing with no effect on step climbing was observed by RAF 25mg/kg (p< 0.05) compared to D/W. Light and dark box test produced increased light box entry and duration by EAF 25mg/kg, RAF 25mg/kg and 50mg/ kg at p<0.05. Furthermore, the hole -board test showed statistically significant increases in number of head dips by EAF 50mg/kg and 100mg/kg as well as RAF 25mg/kg, 50mg/kg and 100 mg/kg at p<0.05. Conclusion: The fractions obtained from Solanum aethiopicum fruits possesses anxiolytic-like activity.


2008 ◽  
Vol 30 (3) ◽  
pp. 215-221 ◽  
Author(s):  
Thiago Zaqueu Lima ◽  
Miriam Marcela Blanco ◽  
Jair Guilherme dos Santos Júnior ◽  
Carolina Tesone Coelho ◽  
Luiz Eugênio Mello

OBJECTIVE: Lithium has been successfully employed to treat bipolar disorder for decades, and recently, was shown to attenuate the symptoms of other pathologies such as Alzheimer's disease, Down's syndrome, ischemic processes, and glutamate-mediated excitotoxicity. However, lithium's narrow therapeutic range limits its broader use. Therefore, the development of methods to better predict its dose becomes essential to an ideal therapy. METHOD: the performance of adult Wistar rats was evaluated at the open field and elevated plus maze after a six weeks treatment with chow supplemented with 0.255%, or 0.383% of lithium chloride, or normal feed. Thereafter, blood samples were collected to measure the serum lithium concentration. RESULTS: Animals fed with 0.255% lithium chloride supplemented chow presented a higher rearing frequency at the open field, and higher frequency of arms entrance at the elevated plus maze than animals fed with a 50% higher lithium dose presented. Nevertheless, both groups presented similar lithium plasmatic concentration. DISCUSSION: different behaviors induced by both lithium doses suggest that these animals had different lithium distribution in their brains that was not detected by lithium serum measurement. CONCLUSION: serum lithium concentration measurements do not seem to provide sufficient precision to support its use as predictive of behaviors.


Dose-Response ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 155932581989126 ◽  
Author(s):  
Hafiz Muhammad Asif ◽  
Abdul Hayee ◽  
Muhammad Rahil Aslam ◽  
Khalil Ahmad ◽  
Abdul Sattar Hashmi

The present work was carried out to assess the Onosma bracteatum anxiolytic and antidepressant properties. Swiss albino mice (male) were fed orally with hydroalcoholic extract at different doses 50, 100, and 200 mg 1 hour prior to test with the standard diazepam and fluoxetine. Anxiolytic and antidepressant activities were evaluated by using open field, elevated plus maze, force swimming, and tail suspension test. Results of open field test showed an increase in number of line crossing as well as number of rearing in dosage-dependent design. Although results of elevated plus maze test evidently showed antianxiety effect of O bracteatum by increasing the time spent in open arms along with decreasing the time spent in closed arms in dosage-dependent way. For the evaluation of antidepressant effect, O bracteatum diminished the immobility time and expanded mobility time in forced swim model in dosage-dependent way. Likewise, O bracteatum expanded time span of mobility along with diminished immobility time in tail suspension method in dosage-dependent way. Outcome demonstrated that plant at the dose of 200 mg/kg body weight showed significant potential which was similar to that standard diazepam and fluoxetine. Hence, O bracteatum may be used as potent natural psychotherapeutic agent against the mental disorders.


2019 ◽  
Vol 168 (1) ◽  
pp. 52-54
Author(s):  
O. O. Masalova ◽  
S. B. Kazakova ◽  
T. N. Savateeva-Lyubimova ◽  
K. V. Sivak ◽  
N. S. Sapronov ◽  
...  

2011 ◽  
Vol 115 (5) ◽  
pp. 979-991 ◽  
Author(s):  
Mitsuyoshi Kodama ◽  
Yasushi Satoh ◽  
Yukiko Otsubo ◽  
Yoshiyuki Araki ◽  
Ryuji Yonamine ◽  
...  

Background In animal models, neonatal exposure to volatile anesthetics induces neuroapoptosis, leading to memory deficits in adulthood. However, effects of neonatal exposure to desflurane are largely unknown. Methods Six-day-old C57BL/6 mice were exposed to equivalent doses of desflurane, sevoflurane, or isoflurane for 3 or 6 h. Minimum alveolar concentration was determined by the tail-clamp method as a function of anesthesia duration. Apoptosis was evaluated by immunohistochemical staining for activated caspase-3, and by TUNEL. Western blot analysis for cleaved poly-(adenosine diphosphate-ribose) polymerase was performed to examine apoptosis comparatively. The open-field, elevated plus-maze, Y-maze, and fear conditioning tests were performed to evaluate general activity, anxiety-related behavior, working memory, and long-term memory, respectively. Results Minimum alveolar concentrations at 1 h were determined to be 11.5% for desflurane, 3.8% for sevoflurane, and 2.7% for isoflurane in 6-day-old mice. Neonatal exposure to desflurane (8%) induced neuroapoptosis with an anatomic pattern similar to that of sevoflurane or isoflurane; however, desflurane induced significantly greater levels of neuroapoptosis than almost equivalent doses of sevoflurane (3%) or isoflurane (2%). In adulthood, mice treated with these anesthetics had impaired long-term memory, whereas no significant anomalies were detected in the open-field and the elevated plus-maze tests. Although performance in a working memory task was normal in mice exposed neonatally to sevoflurane or isoflurane, mice exposed to desflurane had significantly impaired working memory. Conclusions In an animal model, neonatal desflurane exposure induced more neuroapoptosis than did sevoflurane or isoflurane and impaired working memory, suggesting that desflurane is more neurotoxic than sevoflurane or isoflurane.


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