scholarly journals GABAA/Benzodiazepine Receptor Complex in the Dorsal Hippocampus Mediates the Effects of Chrysin on Anxiety-Like Behaviour in Female Rats

2022 ◽  
Vol 15 ◽  
Author(s):  
Juan Francisco Rodríguez-Landa ◽  
Fabiola Hernández-López ◽  
Lucía Martínez-Mota ◽  
Damiana Scuteri ◽  
Blandina Bernal-Morales ◽  
...  

Systemic injections of the flavonoid chrysin (5,7-dihydroxyflavone) exert anxiolytic-like effects in ovariectomised and cycling female rats through actions on gamma-aminobutyric acid-A (GABAA) receptors; however, it is unknown if chrysin directly acts on brain structures that are involved in regulating emotional processes, such as the hippocampus. The present study evaluated the effects of intrahippocampal microinjections of 0.25, 0.5, and 1 μg of chrysin on anxiety-like behaviour in the elevated plus maze (EPM) and locomotor activity test (LAT) in female rats in proestrus and dioestrus. Similar doses of the neurosteroid allopregnanolone were used as a reference GABAergic anxiolytic drug. The participation of the GABAA/benzodiazepine receptor complex was evaluated by administering the antagonists picrotoxin, bicuculline and flumazenil. In proestrus, 0.5 and 1 μg of chrysin and allopregnanolone induced anxiogenic-like behaviour. In dioestrus, chrysin, and allopregnanolone (0.5 μg) induced anxiolytic-like effects. Picrotoxin, bicuculline and flumazenil prevented the effects of chrysin and allopregnanolone in both proestrus and dioestrus. None of the treatments significantly affected locomotor activity. These results indicate that the GABAA/benzodiazepine receptor complex in the dorsal hippocampus regulates the effects of chrysin on anxiety-like behaviour, similar to the actions of allopregnanolone. The divergent effects of treatments across the oestrous cycle phases suggest complex interactions between GABAA receptors and compounds with an anxiolytic potential.

2021 ◽  
Author(s):  
Adriaan W. Bruijnzeel ◽  
Azin Behnood-Rod ◽  
Wendi Malphurs ◽  
Ranjithkumar Chellian ◽  
Robert M. Caudle ◽  
...  

AbstractThe prescription opioid oxycodone is widely used for the treatment of pain in humans. Oxycodone misuse is more common among people with an anxiety disorder than those without one. Therefore, oxycodone might be misused for its anxiolytic properties. We investigated if oxycodone affects anxiety-like behavior in adult male and female rats. The rats were treated with oxycodone (0.178, 0.32, 0.56, or 1 mg/kg), and anxiety-like behavior was investigated in the elevated plus-maze test. Immediately after the elevated plus-maze test, a small open field test was conducted to determine the effects of oxycodone on locomotor activity. In the elevated plus-maze test, oxycodone increased the percentage of time spent on the open arms, the percentage of open arm entries, time on the open arms, open arm entries, and the distance traveled. The males treated with vehicle had a lower percentage of open arm entries than the females treated with vehicle, and oxycodone treatment led to a greater increase in the percentage of open arm entries in the males than females. Furthermore, the females spent more time on the open arms, made more open arm entries, spent less time in the closed arms, and traveled a greater distance than the males. In the small open field test, treatment with oxycodone did not affect locomotor activity or rearing. Sex differences were observed; the females traveled a greater distance and displayed more rearing than the males. In conclusion, oxycodone decreases anxiety-like behavior in rats, and oxycodone has a greater anxiolytic-like effect in males than females.


2011 ◽  
Vol 26 (S2) ◽  
pp. 436-436
Author(s):  
M.R. Zarrindast ◽  
M. Nasehi ◽  
N. Heidari ◽  
A. Torkaman Boutorabi

IntroductionSome investigations showed that the glutamate receptors have critical role for cognition such as learning and anxiety in the brain.ObjectivesThe possible involvement of cholinergic system of dorsal hippocampus in the anxiolytic-like response induced by NMDA receptor antagonist, MK801 has been investigated in the present study.MethodsThe male wistar rats were used and the elevated plus maze apparatus has been used to test parameters (%OAT, %OAE, locomotor activity, grooming, rereading and defection) of anxiety-like behaviors.ResultsThe data indicated that intra-CA1 administration of MK801 (2 μg/rat) increased %OAT and %OAE but did not other exploratory behaviors, indicating an anxiolytic-like response. Moreover, intra-hippocampal injection of cholinergic receptor antagonists, mecamylamine (2 μg/rat) and scopolamine (4 μg/rat) by itselves, 5 min before testing increased %OAT and %OAE, but did not alter locomotor activity and other exploratory behaviors, suggesting anxiolytic-like behavior. On the other hand, intra-CA1 co-administration of ineffective doses of scopolamine (3 μg/rat), but not mecamylamine (1 μg/rat) with ineffective dose of MK801 (1 μg/rat) increased %OAT and %OAE.ConclusionThe data may indicate that the possible involvement of cholinergic system of CA1 on anxiolytic-like response induced by MK801.


2019 ◽  
Vol 3 ◽  
pp. 247054701989703
Author(s):  
Jorge A. Sierra-Fonseca ◽  
Lyonna F. Parise ◽  
Francisco J. Flores-Ramirez ◽  
Eden H. Robles ◽  
Israel Garcia-Carachure ◽  
...  

Background Anxiety disorders are the most common neuropathologies worldwide, but the precise neuronal mechanisms that underlie these disorders remain unknown. The hippocampus plays a role in mediating anxiety-related responses, which can be modeled in rodents using behavioral assays, such as the elevated plus maze. Yet, the molecular markers that underlie affect-related behavior on the elevated plus maze are not well understood. Methods We used herpes simplex virus vector delivery to overexpress extracellular signal-regulated kinase-2, a signaling molecule known to be involved in depression and anxiety, within the dorsal hippocampus of adult Sprague-Dawley male rats. Three days post virus delivery, we assessed anxiety-like responses on the elevated plus maze or general locomotor activity on the open field test. Results When compared to controls, rats overexpressing extracellular signal-regulated kinase-2 in the dorsal hippocampus displayed an anxiolytic-like phenotype, per increases in time spent in the open arms, and less time in the closed arms, of the elevated plus maze. Furthermore, no changes in locomotor activity as a function of virus infusion were observed on the open field test between the experimental groups. Conclusion This investigation demonstrates that virus-mediated increases of extracellular signal-regulated kinase-2 signaling, within the hippocampus, plays a critical role in decreasing anxiogenic responses on the rat elevated plus maze. As such, our data provide construct validity, at least in part, to the molecular mechanisms that mediate anxiolytic-like behavior in rodent models for the study of anxiety.


2019 ◽  
Author(s):  
León Jesús German-Ponciano ◽  
Bruna Patrícia Dutra Costa ◽  
Leonardo Miranda Feitosa ◽  
Kimberly dos Santos Campos ◽  
Suianny Nayara da Silva Chaves ◽  
...  

AbstractChrysin (5,7-dihydroxyflavone), a nutraceutical flavonoid present in diverse plants, has a backbone structure shared with the flavone backbone, with additional hydroxyl groups that confers its antioxidant properties and effects at the GABAA receptor complex. However, whether these effects are due to the hydroxyl groups is unknown. Here we report the effects of chrysin or the flavone backbone (1 mg/kg) in rats subjected to the elevated plus-maze and the locomotor activity test, as well as in the zebrafish evaluated in light/dark model. Chrysin, but not flavone, increased entries and time in the open arms of the elevated plus-maze, as well as time on white compartment of the light/dark model in zebrafish. These effects were comparable to diazepam, and were devoid of motor effects in both tests, as well as in the locomotor activity test. On the other hand, flavone decreased risk assessment in the light/dark test but increased rearing in the locomotor activity test in rats, suggesting effects threat information gathering; important species differences suggest new avenues of research. It is suggested that the specific effects of chrysin in relation to flavone include more of a mechanism of action in which in addition to its action at the GABAA/benzodiazepine receptor complex also could be involved its free radical scavenging abilities, which require specific research.Preprinthttps://doi.org/10.1101/575514;Data and scriptshttps://github.com/lanec-unifesspa/chrysin


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