Pinealectomy and Exogenous Melatonin Regulate Anxiety-Like and Depressive-Like Behaviors in Male and Female Wistar Rats

Zahra, El Mrabet Fatima; Siham, Ouaaki; Mesfioui, Abdelhalem; Aboubakr, El Hessni; Ouichou, Ali

doi:10.4236/nm.2012.34049

Cited by 16 publications

(7 citation statements)

References 50 publications

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“…In addition, we have clearly demonstrated that the antidepressant-like activity of MEL was dose-dependent, since TIM is greatly reduced at 16 mg/kg than at 2 mg/kg dose. These results are in good agreement with data reported with our previous observations showing that chronic administration of MEL produced a real power antidepressant-like [12,13]. A similar reduction of swimming in the FST has been previously observed by Brotto et al [46].…”

Section: Discussionsupporting

confidence: 93%

“…In addition, we have shown that this anxiolytic-like activity of MEL depends on the used dose of the pineal hormone, its effectiveness increasing with the concentration, since its effect is greater at 16 mg/kg than at 2 mg/ kg. These results are entirely consistent with our previous observations showing that MEL caused an anxiolytic-like effect in rats [12,13]. Except study of Wong and Ong [41] in mice, showing that MEL was unable to produce any anxiolytic effectin OFT, majority, if not all other works have reported a significant reduction in anxiety behavior in animals treated with pharmacological doses of MEL, whatever the experimental conditions used or anxiogenic situations.…”

Section: Discussionsupporting

confidence: 93%

“…In rodents, preclinical studies have shown that MEL exercised antidepressant-like and anxiolytic-like in animal models of anxiety, such as passive avoidance test, OFT and EPM tests, and light/dark box, such tests known for their ability to cause anxiety under presence of aversive stimuli [9][10][11]. Recently, we reported in two separate studies that: 1) chronic administration of MEL induced anxiolytic-like effect in OFT and EPM paradigms and antidepressant-like effect in FST test, such effects were depending on sex hormones [12] and 2) suppression of the synthesis of endogenous MEL by pinealectomy increases levels of anxiety-like and depression-like, confirming the anxiolytic-like and antidepressant-like nature of MEL [13]. Kopp et al [11] have also shown that MT1/MT2 receptors agonist (S 23478) were effective in the free exploration test and light/dark box, whereas MT3 receptor agonists are less or not effective under the same experimental conditions [11].…”

Section: Introductionmentioning

confidence: 82%

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Melatonin and Diazepam Affect Anxiety-Like and Depression-Like Behavior in Wistar Rats: Possible Interaction with Central GABA Neurotransmission

Ouakki¹,

Mrabet²,

Lagbouri³

et al. 2013

JBBS

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Recent studies have shown the importance of the GABA-ergic transmission in the pathophysiology of anxiety and depressive disorders in humans. Our present study aims to investigate the interaction of melatonin (MEL) with this system by exploring the effects of MEL with or without a facilitator of GABA-ergic neurotransmission, diazepam (DZ) on the levels of depression and anxiety in Wistar rats. For this purpose, different doses of MEL (2, 4 or 16 mg/kg) or DZ (2 mg/kg) are subchronically administered during 15 days. After pharmacological treatments, anxiety levels are evaluated in behavioral tests of Open Field (OFT) and elevated plus maze (EPM) and depression levels are evaluated by the forced swim test (FST). The results showed that MEL produces anxiolytic-like and antidepressant-like effects in a dosedependent manner; the maximum effect was obtained at a dose of 16 mg/kg. However, a dose of 4 mg/kg is necessary to induce an effect. The effect of MEL and DZ reported in this study concerns selective modulation of behavioral anxiety and depression since locomotor activity assessed by the OFT and EPM was not affected. The subchronic injection of MEL at 4 mg/kg, DZ at 2 mg/kg or the two combined molecules also induces also anxiety-like and antidepressant-like behavior. In addition, a potentiating effect between MEL and DZ was observed. These effects suggest that psychopharmacological actions of MEL are due, at least in part, to its ability to improve the central GABA-ergic transmission.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 82%

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Melatonin and Diazepam Affect Anxiety-Like and Depression-Like Behavior in Wistar Rats: Possible Interaction with Central GABA Neurotransmission

Ouakki¹,

Mrabet²,

Lagbouri³

et al. 2013

JBBS

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“…The enhanced anxiety resulting from pineal gland removal detected a month after the surgery procedure, was confirmed in two different tests-OF and EPM. However, our previous results and literature data demonstrated a divergence with a lack of effect on anxiety, anxiolysis, or anxiogenic response resulting from pinealectomy [ 49 , 50 , 51 , 52 , 53 ]. This suggests that the difference in the strain and the testing time after pinealectomy might be an important issue determining this behavioral response.…”

Section: Discussionmentioning

confidence: 76%

The Role of Melatonin on Behavioral Changes and Concomitant Oxidative Stress in icvAβ1-42 Rat Model with Pinealectomy

Tzoneva

Georgieva

Ivanova

et al. 2021

IJMS

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One of the pathological hallmarks of Alzheimer’s disease (AD) associated with its progression that contributes to β-amyloid (Aβ) generation is oxidative stress (OS). Clinical data suggest that melatonin is a potent antioxidant that might be effective in the adjunctive therapy of this neurodegenerative disease. The present study aimed to explore the role of melatonin on behavioral changes and markers of OS in three rat models, namely, pinealectomy (pin) model of melatonin deficit, intracerebroventricular (icv)Aβ1-42 model of AD, and combination of both pin and Aβ1-42 model (pin+icvAβ1-42). The chronic injection with vehicle/melatonin (50 mg/kg, i.p. for 40 days) started on the same day of sham/pin and icv vehicle/Aβ1-42 infusion procedures. Anxiety in the open field and the elevated plus-maze test and cognitive responses in the object recognition test were tested between the 30th–35th day after the surgical procedures. Markers of OS in the frontal cortex (FC) and hippocampus were detected by the ELISA method. Melatonin treatment corrected the exacerbated anxiety response only in the pin+icvAβ1-42 model while it alleviated the cognitive impairment in the three models. Pinealectomy disturbed the antioxidant system via enhanced SOD activity and decreased GSH levels both in the FC and hippocampus. The Aβ1-42 model decreased the SOD activity in the FC and elevated the MDA level in the two brain structures. The pin+icvAβ1-42 model impaired the antioxidant system and elevated lipid peroxidation. Melatonin supplementation restored only the elevated MDA level of icvAβ1-42 and pin+icvAβ1-42 model in the hippocampus. In conclusion, our study reveals that the pin+icvAβ1-42 rat model triggers more pronounced anxiety and alterations in markers of OS that may be associated with melatonin deficit concomitant to icvAβ1-42-induced AD pathology.

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“…caused behavioral anomalies such as an increase in anxiety-like and depressive-like behavior (Zahra, Siham, Abdelhalim, Aboubakr, & Ali, 2012).…”

Section: Discussionmentioning

confidence: 99%

Melatonin Modulates Interval Timing in Rats: Effect of Pinealectomy

Bussi¹,

Levin²,

Golombék³

et al. 2015

IJCP

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Interval timing is a complex cognitive process that involves the estimation of time within the seconds-to-minutes range. This temporal processing depends on cortico-striatal interactions, as well as an optimal dopaminergic function. On the other hand, the circadian system controls physiological and behavioral functions with periods close to 24 hr. We have previously reported that short-time perception in mice is influenced by the circadian pacemaker, with dopamine signaling as a link between both temporal systems. In this work we evaluated the involvement of melatonin in the circadian modulation of interval timing, as well as the interaction between this hormone and dopamine levels in the striatum. We report that melatonin-depleted rats, by pinealectomy, present an impairment in their ability to estimate a short (24 s) target duration in the peak-interval procedure. Moreover, melatonin administration in drinking water restores interval timing precision in pinealectomized rats. We also show that circadian desynchronization causes a transient impairment in the timing task. In addition, melatonin administration affects interval timing only when rats are trained and tested during the night. Furthermore, we report that melatonin depletion increases striatal dopamine availability, which is reverted by external melatonin administration. Taken together, our findings add further support to the notion that the circadian system modulates interval timing, probably by using melatonin as an output to regulate dopaminergic functions in brain areas that are important for interval timing mechanisms.

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Pinealectomy and Exogenous Melatonin Regulate Anxiety-Like and Depressive-Like Behaviors in Male and Female Wistar Rats

Cited by 16 publications

References 50 publications

Melatonin and Diazepam Affect Anxiety-Like and Depression-Like Behavior in Wistar Rats: Possible Interaction with Central GABA Neurotransmission

Melatonin and Diazepam Affect Anxiety-Like and Depression-Like Behavior in Wistar Rats: Possible Interaction with Central GABA Neurotransmission

The Role of Melatonin on Behavioral Changes and Concomitant Oxidative Stress in icvAβ1-42 Rat Model with Pinealectomy

Melatonin Modulates Interval Timing in Rats: Effect of Pinealectomy

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