Effects of agomelatine in a murine model of obsessive–compulsive disorder: Interaction with <i>meta</i>‐chlorophenylpiperazine, bicuculline, and diazepam

Bhutada, Pravinkumar; Dixit, Pankaj; Thakur, Kapil; Deshmukh, Prashant; Kaulaskar, Shyam

doi:10.1016/j.kjms.2012.11.003

Cited by 12 publications

(3 citation statements)

References 17 publications

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“…Namely, mCPP, a 5-HT2C agonist, which in humans, has been observed to exacerbate symptoms of OCD in untreated patients (Gross-Isseroff et al, 2004) and in rodent RRBs (Reimer et al, 2018). Most studies exploring mCPP have observed increases in stereotypic behavior, commonly evaluated through repetitive grooming and marble burying and particularly at higher doses of 1 and 3 mg/kg (Bhutada et al, 2013;Wright and Rodgers, 2014). Moreover, Kantor et al (2000) observed self-grooming behavior during a social interaction paradigm, finding that administration of mCPP in three separate rat strains enhanced self-grooming.…”

Section: -Ht2cmentioning

confidence: 99%

Impact of specific serotonin receptor modulation on restricted repetitive behaviors

Alvarez

Cavazos

Morales

et al. 2022

Front. Behav. Neurosci.

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Restricted, repetitive behaviors (RRBs) are commonly divided into two behavioral categories, lower-order and higher-order RRBs. Individuals displaying lower-order motoric RRBs may express repetitive hand flapping behaviors, body rocking back and forth movements, and continuous body spinning. Higher-order RRBs most commonly cover the behavior inflexibility and cognitive rigidity commonly found in disorders such as autism spectrum disorder and obsessive-compulsive disorder. Various neuropsychiatric disorders are plagued by RRBs yet no FDA-approved treatments have been identified. In rodents, lower-order RRBs are commonly measured through various tasks, such as repetitive self-grooming, marble burying, and stereotypic motor behaviors. This review focuses on the effects that modulation of specific serotonin receptors have on lower-order RRBs. Although there is research examining how changes in 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT6, and 5-HT7 receptor modulation, more research has focused on the 5-HT1A, 5-HT2A, and 5-HT2C receptors. The accumulating data suggest that increasing 5-HT1A activation decreases RRBs while blocking 5-HT1A activation has no effect on RRBs. While there are mixed findings regarding the impact of 5-HT2A modulation on RRBs, the general trend shows mixed effects of 5-HT2A receptor activation RRB expression, whereas blockade generally decreases RRBs. 5-HT2C receptor activation can modulate RRBs in either direction depending on the 5-HT2C drug used, blocking 5-HT2C activation only seems to show therapeutic properties when 5-HT2C activation is already elevated. The other 5-HT receptors have been explored far less but show promise as potential targets for regulating RRBs. Although it is less clear due to the involvement of 5-HT1D, 5-HT1A activation increases RRBs, and blocking 5-HT1A tends to decrease RRBs. 5-HT2B activation could reduce RRBs, while inhibiting 5-HT2B does not impact RRBs. Increasing 5-HT3 has not been shown to affect RRBs. Yet, increases in RRBs have been observed in Htr3a KO mice. 5-HT6 receptor activation can increase RRBs, while blocking 5-HT6 activity tends to decrease RRBs. Lastly, neither increasing or blocking 5-HT7 activity can reduce RRBs. In sum, there is no uniform pattern in whether all specific 5-HT receptors affect RRBs in either direction, instead, there is evidence suggesting that different 5-HT receptors can modulate RRBs in different directions. Further researching the less explored receptors and aiming to understand why these receptors can differently modulate RRBs, may play a key role in developing therapeutics that treat RRBs.

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Section: -Ht2cmentioning

confidence: 99%

Impact of specific serotonin receptor modulation on restricted repetitive behaviors

Alvarez

Cavazos

Morales

et al. 2022

Front. Behav. Neurosci.

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Section: Obsessive-compulsive Disordermentioning

confidence: 99%

“…Another study, in 2013, also highlighted the potential anticompulsive effect of agomelatine [79]. Anticompulsive effect of agomelatine is reported to be mediated via 5HT2C antagonism and MT1/2 agonism [79]. Thus, melatonergic agents could be promising and may be developed for possible use in OCD in conjunction with existing medications.…”

Section: Obsessive-compulsive Disordermentioning

confidence: 99%

Advancing role of melatonin in the treatment of neuropsychiatric disorders

Mahmood

Muhammad

Alghani

et al. 2016

Egyptian Journal of Basic and Applied Sciences

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Melatonin is a pineal neurohormone whose secretion is influenced by circadian changes of 24 hour night and day cycle. Over the recent past, several studies have highlighted the ubiquitous influence of the circadian timing in almost all the physiologic functions. An altered/ deficient sleep-wake cycle has been correlated with physiological imbalances which are linked to the development of various disorders, viz depression, anxiety, psychosis, attention deficits, sleep deprivation and others. Melatonin and its oxidation products, viz cyclic 3-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykinuramine and N1-acetyl-5methoxykinuramine possess excellent antioxidant properties. Melatonin's beneficial neuroprotective properties are mostly attributed to excellent free radical scavenging properties. A gathering body of evidence has shown that besides strong antioxidant activities, melatonin is a pleiotropic regulator molecule which orchestrates multiple functions through all the three melatonin receptors, i.e. MT1, MT2, and MT3. For example, MT2 receptor agonistic activity is attributed to neuroprotective, hypnotic and anxiolytic properties while MT1 and MT2 agonistic activity is associated with the clinical efficacy of agomelatine. The third melatonin receptor has been identified as quinone reductase (QR) 2, an enzyme involved in detoxification. MT3 agonist has been linked to strong hypotensive effects in preclinical study.In conclusion, the gathering body of evidence both from preclinical and clinical literatures suggests strong antioxidant activities and diverse pleiotropic mechanisms of melatonin for potential neuroprotective role in diverse neuropsychiatric disorders. However, there is still a lack of melatonergic ligands with high selectivity and specificity to precisely target any particular neuropsychiatric disorders for which limited therapeutic options are currently available clinically.

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