Concussion can increase the risk of visually induced motion sickness.

Concussion can lead to various symptoms such as balance problems, memory impairments, dizziness, and/or headaches. It has been previously suggested that during self-motion relevant tasks, individuals with concussion may rely heavily on visual information to compensate for potentially less reliable vestibular inputs and/or problems with multisensory integration. As such, concussed individuals may also be more sensitive to other visually-driven sensations such as visually induced motion sickness (VIMS). To investigate whether concussed individuals are at elevated risk of experiencing VIMS, we exposed participants with concussion (n = 16) and healthy controls (n = 15) to a virtual scene depicting visual self-motion down a grocery store aisle at different speeds. Participants with concussion were further separated into symptomatic and asymptomatic groups. VIMS was measured with the SSQ before and after stimulus exposure, and visual dependence, self-reported dizziness, and somatization were recorded at baseline. Results showed that concussed participants who were symptomatic demonstrated significantly higher SSQ scores after stimulus presentation compared to healthy controls and those who were asymptomatic. Visual dependence was positively correlated with the level of VIMS in healthy controls and participants with concussion. Our results suggest that the presence of concussion symptoms at time of testing significantly increased the risk and severity of VIMS. This finding is of relevance with regards to the use of visual display devices such as Virtual Reality applications in the assessment and rehabilitation of individuals with concussion.

Improvement of acceptability in patients undergoing esophagogastroduodenoscopy using auditory and visual stimulation.

Esophagogastroduodenoscopy (EGD) has become an indispensable examination to discover upper gastrointestinal diseases, including cancer, and perform endoscopic treatment. However, many individuals who undergo the procedure have feelings of anxiety and fear regarding EGD. Although the use of medication for sedation during EGD is useful for reducing anxiety and the stability of hemodynamics, sedation may increase the likelihood of complications. Several noninvasive distractions have been introduced to decrease pain and anxiety during endoscopic examinations;however, most assessments of these distractions evaluated subjective items such as impression. We herein add the results of our studies using objective items and review the effectiveness of distractions for EGD. J. Med. Invest. 69 : 8-18, February, 2022.

[Self-induced epileptic seizures: Prevalence, Causes and Treatment]. / Selbstinduzierte epileptische Anfälle Prävalenz, Ursachen und Behandlung.

Self-induced seizures were first described in 1827. A majority of authors found that in unselected patients with epilepsy, the prevalence rate of these seizures was 1%. In patients with photosensitive epilepsy, there was roughly a 25% prevalence. Apart from visual stimulation, many other mechanisms of self-induction have been described. A feeling of pleasure or relaxation during seizures may be a reason for self-inductive behaviour. But often the procedure of self-induction is experienced as involuntary. Treatment is always difficult. Behavioral therapy has been proven effective in some patients. In patients with photosensitive epilepsy, sunglasses are recommended. Fenfluramine, clonazepam and valproate seem to be a bit more effective than other drugs. After all, the treatment effect depends on the motivation of the patient to change the condition.

Flashing lights and epileptic spasms: should we be routinely performing intermittent photic stimulation in infants?

Abnormal cortical excitation in response to photic stimulation (photosensitivity) has historically been associated with generalized epilepsies, in patients outside of infancy. At our tertiary centre, we encountered a patient with infantile spasms secondary to a mutation in ALG13 (c320A>G) who had photic stimulation-induced epileptic spasms over a broad range of frequencies on multiple EEGs, which were worse without treatment and decreased as treatment was escalated. This is the first reported case of epileptic spasms triggered by photic stimulation and it is unclear whether the phenomenon is unique to this patient, to those with this mutation or whether it is present in a broader group of patients with infantile spasms.

Altered states phenomena induced by visual flicker light stimulation.

Flicker light stimulation can induce short-term alterations in consciousness including hallucinatory color perception and geometric patterns. In the study at hand, the subjective experiences during 3 Hz and 10 Hz stroboscopic light stimulation of the closed eyes were assessed. In a within-subjects design (N = 24), we applied the Positive and Negative Affect Schedule (mood state), time perception ratings, the Altered State of Consciousness Rating Scale, and the Phenomenology of Consciousness Inventory. Furthermore, we tested for effects of personality traits (NEO Five-Factor Inventory-2 and Tellegen Absorption Scale) on subjective experiences. Such systematic quantification improves replicability, facilitates comparisons between pharmacological and non-pharmacological techniques to induce altered states of consciousness, and is the prerequisite to study their underlying neuronal mechanisms. The resulting data showed that flicker light stimulation-induced states were characterized by vivid visual hallucinations of simple types, with effects strongest in the 10 Hz condition. Additionally, participants' personality trait of Absorption scores highly correlated with the experienced alterations in consciousness. Our data demonstrate that flicker light stimulation is capable of inducing visual effects with an intensity rated to be similar in strength to effects induced by psychedelic substances and thereby support the investigation of potentially shared underlying neuronal mechanisms.

Chronic optogenetic stimulation of Bergman glia leads to dysfunction of EAAT1 and Purkinje cell death, mimicking the events caused by expression of pathogenic ataxin-1.

Bergmann glia (BG) are highly specialized radial astrocytes of the cerebellar cortex, which play a key role in the uptake of synaptic glutamate via the excitatory amino acid transporter EAAT1. Multiple lines of evidence suggest that in cerebellar neurodegenerative diseases reactive BG has a negative impact on neuronal function and survival through compromised EAAT activity. A family of such diseases are those caused by expansion of CAG repeats in genes of the ataxin family, resulting in spinocerebellar ataxias (SCA). We investigated the contribution of BG to the pathogenesis of cerebellar neurodegeneration in a model of SCA1, which was induced by expression of a polyglutamine mutant of ataxin-1 (ATXN1[Q85]) in BG specifically. We compared the outcomes with a novel model where we triggered excitotoxicity by a chronic optogenetic activation of BG with channelrhodopsin-2 (ChR2). In both cases we detected evidence of reduced glutamate uptake manifested by prolongation of excitatory postsynaptic currents in Purkinje cells which is consistent with documented reduction of expression and/or function of EAAT1. In both models we detected astroglyosis and Purkinje cells atrophy. Finally, the same pattern was detected in a knock-in mouse which expresses a polyglutamine mutant ataxin-1 ATXN1[Q154] in a non-cell-selective manner. Our results suggest that ATXN1[Q85] and ChR2-induced insult targeted to BG closely mimics SCA1 pathology, where excessive glutamate signaling appears to be a common feature likely being an important contributor to cerebellar neurodegeneration.

Television-induced electronegative photoparoxysmal response: an extratemporal seizure mimic?

Video-EEG monitoring is an established gold-standard procedure for diagnosis and differentiation of epileptic and non-epileptic seizures. Epilepsy misdiagnosis, to which factors such as EEG artifact misinterpretation contribute to, is common, and can have long-lasting iatrogenic repercussions to the clinical management of affected patients. Among the many types of responses to photic stimulation, artifacts and physiologic and epileptic responses are possible. All of these can interfere with EEG interpretation when provoked by a source of illumination. Photic-induced responses are of increasing relevance given the ubiquity of screens and other light-emitting electronics in our modern world. One of these, the photoparoxysmal response, is a frequent finding in photosensitive patients with genetic generalized epilepsies. Various responses beyond abnormal occurrence of cortical spikes or spike-and-wave discharges are known to occur on EEG in response to intermittent photic stimulation (IPS), with different clinical implications. To our knowledge, we report a unique electronegative photoparoxysmal response during video-EEG monitoring induced by fluctuating illumination caused by a distant television screen. This response mimicked an extratemporal seizure in a young woman with frontal lobe epilepsy, admitted for presurgical evaluation. Novel electronegative responses to electronic devices during video-EEG monitoring merit consideration by EEG interpreters to help avoid misdiagnosis.

Photosensitive Self-Induced Seizures Since Childhood.

A 15-year-old girl was admitted to the emergency room because of a bilateral tonic-clonic seizure. The family reported that the episode began with rapid hand movements in front of the patient's eyes while staring at the sun. The patient has a history of multiple admissions in the emergency department due to similar events since the age of eight. Most occurrences were associated with episodes of frustration. The review of the literature has shown that this type of phenomenon, designated in some studies by sunflower syndrome, may be overlooked in patients with photosensitive epilepsy. Despite the unknown etiology, there are several reasons why patients experience this type of behavior, and thus a multidisciplinary approach is needed.

Uma jovem de 15 anos foi admitida no Serviço de Urgência após ter sofrido crise epiléptica tónico-clónica bilateral. A família relatou que o episódio surgiu na sequência de ter iniciado movimentos rápidos das mãos na frente dos olhos enquanto olhava para o sol. A doente havia sido assistida, por diversas vezes, no Serviço de Urgência, devido a eventos semelhantes, desde os oito anos de idade. A maioria dos episódios estava associada a episódios de frustração. A revisão da literatura mostrou que esse tipo de fenómeno, designado em alguns estudos por sunflower syndrome, pode ser desvalorizado em doentes com epilepsia fotossensível. Apesar da etiologia desconhecida, existem várias razões pelas quais os doentes apresentam este tipo de comportamento, enfatizando a necessidade de uma abordagem multidisciplinar.

Binding of the synaptic vesicle radiotracer [11C]UCB-J is unchanged during functional brain activation using a visual stimulation task.

The positron emission tomography radioligand [11C]UCB-J binds to synaptic vesicle glycoprotein 2 A (SV2A), a regulator of vesicle release. Increased neuronal firing could potentially affect tracer concentrations if binding site availability is altered during vesicle exocytosis. This study assessed whether physiological brain activation induces changes in [11C]UCB-J tissue influx (K1), volume of distribution (VT), or binding potential (BPND). Healthy volunteers (n = 7) underwent 60-min [11C]UCB-J PET scans at baseline and during intermittent presentation of 8-Hz checkerboard visual stimulation. Sensitivity to intermittent changes in kinetic parameters was assessed in simulations, and visual stimulation was repeated using functional magnetic resonance imaging to characterize neural responses. VT and K1 were determined using the one-tissue compartment model and BPND using the simplified reference tissue model. In primary visual cortex, K1 increased 34.3 ± 15.5% (p = 0.001) during stimulation, with no change in other regions (ps > 0.12). K1 change was correlated with fMRI BOLD response (r = 0.77, p = 0.043). There was no change in VT (-3.9 ± 8.8%, p = 0.33) or BPND (-0.2 ± 9.6%, p = 0.94) in visual cortex nor other regions (ps > 0.19). Therefore, despite robust increases in regional tracer influx due to blood flow increases, binding measures were unchanged during stimulation. [11C]UCB-J VT and BPND are likely to be stable in vivo measures of synaptic density.

Impaired response of cerebral oxygen metabolism to visual stimulation in Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disease caused by a CAG triplet repeat expansion in the Huntingtin gene. Metabolic and microvascular abnormalities in the brain may contribute to early physiological changes that subserve the functional impairments in HD. This study is intended to investigate potential abnormality in dynamic changes in cerebral blood volume (CBV) and cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO2) in the brain in response to functional stimulation in premanifest and early manifest HD patients. A recently developed 3-D-TRiple-acquisition-after-Inversion-Preparation magnetic resonance imaging (MRI) approach was used to measure dynamic responses in CBV, CBF, and CMRO2 during visual stimulation in one single MRI scan. Experiments were conducted in 23 HD patients and 16 healthy controls. Decreased occipital cortex CMRO2 responses were observed in premanifest and early manifest HD patients compared to controls (P < 0.001), correlating with the CAG-Age Product scores in these patients (R2 = 0.4, P = 0.001). The results suggest the potential value of this reduced CMRO2 response during visual stimulation as a biomarker for HD and may illuminate the role of metabolic alterations in the pathophysiology of HD.

From "Aha!" to "Haha!" Using Humor to Cope with Negative Stimuli.

Humor has been considered an effective emotion regulation strategy, and some behavioral studies have examined its superior effects on negative emotion regulation. However, its neural mechanisms remain unknown. Our functional magnetic resonance imaging study directly compared the emotion regulation effects and neural bases of humorous coping (reappraisal) and ordinary reappraisal following exposure to negative pictures. The behavioral results suggested that humorous reappraisal was more effective in downregulating negative emotions and upregulating positive emotions both in the short and long term. We also found 2 cooperative neural pathways involved in coping with negative stimuli by means of humor: the "hippocampal-thalamic-frontal pathway" and the "amygdala-cerebellar pathway." The former is associated with the restructuring of mental representations of negative situations and accompanied by an insightful ("Aha!") experience, while the latter is associated with humorous emotional release and accompanied by an expression of laughter ("Haha!"). Furthermore, the degree of hippocampal functional connectivity with both the thalamus and frontal cortex was positively correlated with changes in positive emotion, and this result implied that the degree of emotion regulation could be strongly directly related to the depth of cognitive reconstruction. These findings highlight that regulating negative emotions with humor involves cognitive restructuring and the release of positive emotions.

Sunflower syndrome: a poorly understood photosensitive epilepsy.

Sunflower syndrome is a rare photosensitive epilepsy which has received little attention in recent medical literature. The historical cases documenting the epilepsy's stereotyped handwaving motion in front of light characterized the behavior as self-inducing seizures via mimic of stroboscopic effect. However, the relationship between handwaving episodes and attendant generalized electroencephalogram abnormalities, and an appreciation of the compulsive attraction the sun and other light sources hold for these patients, suggest the handwaving motion may be a part of the seizure rather than a mechanism of self-induction. The lack of awareness of Sunflower syndrome often leads to misdiagnosis. The seizures are often refractory to traditional anticonvulsant medication, and patients resort to behavioral intervention, such as hats and sunglasses, to reduce handwaving episodes. Further study is required to determine the syndrome's natural history and to identify more effective treatment options. WHAT THIS PAPER ADDS: Sunflower syndrome is a rare condition that is often misdiagnosed. Awareness of the clinical and electroencephalogram characteristics of Sunflower syndromemay reduce the prevalence of misdiagnosis.

Test-retest reliability of the virtual reality sickness evaluation using electroencephalography (EEG).

No reliable quantitative and objective measurement method for virtual reality (VR) sickness has been firmly established to date. Electroencephalography (EEG) may be a strong candidate to evaluate VR sickness objectively. However, no test-retest evaluation has been made for VR sickness using EEG. To recruit VR sickness-sensitive participants, we tested 858 participants (age = 20's-50's) using the Motion Sickness Susceptibility Questionnaire (MSSQ). Among them, we recruited 21 males (average age = 25.0) who obtained the 75th percentile of scores on the MSSQ (32.9 ± 5.7). VR sickness was evaluated twice (one week apart) using EEG with VR video content designed to cause VR sickness. A Simulation Sickness Questionnaire (SSQ) was also used to evaluate VR sickness. In terms of the reliability of EEG, ICC and Cronbach's alpha analyses showed that three waves (delta, theta, and alpha) were consistent in two areas (frontal and central). A significant difference in EEG was also found repeatedly between the baseline and VR sickness (delta, theta, and alpha) in two areas (frontal and central). We evaluated EEG for its reliability and found specific waves and areas that showed good consistency and significant changes associated with VR sickness. These findings may support further research of VR sickness evaluation.

Protective Effects of Flavonoids in Acute Models of Light-Induced Retinal Degeneration.

Degeneration of photoreceptors caused by excessive illumination, inherited mutations, or aging is the principal pathology of blinding diseases. Pharmacological compounds that stabilize the visual receptor rhodopsin and modulate the cellular pathways triggering death of photoreceptors could avert this pathology. Interestingly, flavonoids can modulate the cellular processes, such as oxidative stress, inflammatory responses, and apoptosis, that are activated during retinal degeneration. As we found previously, flavonoids also bind directly to unliganded rod opsin, enhancing its folding, stability, and regeneration. In addition, flavonoids stimulate rhodopsin gene expression. Thus, we evaluated the effect of two main dietary flavonoids, quercetin and myricetin, in ATP-binding cassette subfamily A member 4 -/- /retinol dehydrogenase 8 -/- and wild-type BALB/c mice susceptible to light-induced photoreceptor degeneration. Using in vivo imaging, such as optical coherence tomography, scanning laser ophthalmoscopy, and histologic assessment of retinal morphology, we found that treatment with these flavonoids prior to light insult remarkably protected retina from deterioration and preserved its function. Using high-performance liquid chromatography-mass spectrometry analysis, we detected these flavonoids in the eye upon their intraperitoneal administration. The molecular events associated with the protective effect of quercetin and myricetin were related to the elevated expression of photoreceptor-specific proteins, rhodopsin and cone opsins, decreased expression of the specific inflammatory markers, and the shift of the equilibrium between cell death regulators BCL2-associated X protein (BAX) and B-cell lymphoma 2 toward an antiapoptotic profile. These results were confirmed in photoreceptor-derived 661W cells treated with either H2O2 or all-trans-retinal stressors implicated in the mechanism of retinal degeneration. Altogether, flavonoids could have significant prophylactic value for retinal degenerative diseases. SIGNIFICANCE STATEMENT: Flavonoids commonly present in food exhibit advantageous effects in blinding diseases. They bind to and stabilize unliganded rod opsin, which in excess accelerates degenerative processes in the retina. Additionally, flavonoids enhance the expression of the visual receptors, rod and cone opsins; inhibit the inflammatory reactions; and induce the expression of antiapoptotic markers in the retina, preventing the degeneration in vivo. Thus, flavonoids could have a prophylactic value for retinal degenerative diseases.

Repetitive Blast Promotes Chronic Aversion to Neutral Cues Encountered in the Peri-Blast Environment.

Repetitive mild traumatic brain injury (mTBI) has been called the "signature injury" of military service members in the Iraq and Afghanistan wars and is highly comorbid with post-traumatic stress disorder (PTSD). Correct attribution of adverse blast-induced mTBI and/or PTSD remains challenging. Pre-clinical research using animal models can provide important insight into the mechanisms by which blast produces injury and dysfunction-but only to the degree by which such models reflect the human experience. Avoidance of trauma reminders is a hallmark of PTSD. Here, we sought to understand whether a mouse model of blast reproduces this phenomenon, in addition to blast-induced physical injuries. Drawing on well-established work from the chronic stress and Pavlovian conditioning literature, we hypothesized that even while one is anesthetized during blast exposure, environmental cues encountered in the peri-blast environment could be conditioned to evoke aversion/dysphoria and re-experiencing of traumatic stress. Using a pneumatic shock tube that recapitulates battlefield-relevant open-field blast forces, we provide direct evidence that stress is inherent to repetitive blast exposure, resulting in chronic aversive/dysphoric-like responses to previous blast-paired cues. The results in this report demonstrate that, although both single and repetitive blast exposures produce acute stress responses (weight loss, corticosterone increase), only repetitive blast exposure also results in co-occurring aversive/dysphoric-like stress responses. These results extend appreciation of the highly complex nature of repetitive blast exposure; and lend further support for the potential translational relevance of animal modeling approaches currently used by multiple laboratories aimed at elucidating the mechanisms (both molecular and behavioral) of repetitive blast exposure.

A study of the significance of photoparoxysmal responses and spontaneous epileptiform discharges in the EEG in childhood epilepsy.

AIM: In clinical practice, there is a prevailing notion that photosensitivity mostly occurs in children with epilepsy (CWE) with idiopathic generalized epilepsy. We investigated the distribution of epilepsy types and etiology in photosensitive children and the associations with specific clinical and electroencephalogram (EEG) variables. METHODS: In this retrospective cohort study, clinical data were acquired from all children that showed photosensitivity during systematic intermittent photic stimulation (IPS), over a 10-year interval at a tertiary level Children's Hospital, Winnipeg. Patient demographics, EEG findings, and clinical data and symptoms during IPS were abstracted. Classification of diagnoses using the International League Against Epilepsy (ILAE) 2017 guidelines was done by an expert panel. RESULTS: Seventy-eight photosensitive children were identified. Forty (51.3%) had generalized epilepsy (idiopathic: 27, structural: 2, other: 11) compared with 19 (24.4%) focal (idiopathic: 1, structural: 2, other: 16), 8 (10.3%) combined focal and generalized (structural: 4, other: 4), and 11 (14.1%) unknown epilepsy (other: 11); (χ2 (3) = 32.1, p = .000). Self-sustaining or outlasting photoparoxysmal responses (PPRs) occurred in association with all epilepsy types; however, the EEGs of focal CWE without treatment comprised almost solely of PPRs which outlasted the stimulus (8/10), in contrast to only 8/17 of focal CWE with treatment and to 13/26 of generalized epilepsy without treatment. Most frequency intervals in individual patients were less under treatment: a decrease in standardized photosensitivity range (SPR) was seen in 5 CWE, an increase in 2, and no change in 1 during treatment. Both CWE with focal and generalized epilepsy showed abnormal activity on EEG during hyperventilation (40% vs 65.7%). Thirteen out of 14 CWE with clinical signs during IPS had independent spontaneous epileptiform discharges (SEDs) in the EEG recording. CONCLUSION: Photosensitivity occurs in all types of epilepsy rather than in idiopathic generalized epilepsy alone. Surprisingly, there is a tendency for focal epilepsy to be associated with self-sustaining PPRs, especially when no treatment is used. Treatment tends to make the PPR more self-limiting and decrease the SPR. There is a tendency that clinical signs during IPS occur in EEGs in individuals with SEDs.

Enhanced noradrenergic activity by yohimbine and differential fear conditioning in patients with major depression with and without adverse childhood experiences.

Major depressive disorder (MDD) has been associated with changes in the biological stress systems, including the locus coeruleus-noradrenergic system. Accumulated evidence suggests an upregulation of central alpha2-receptors, leading to decreased noradrenergic activity on a central level in MDD patients. Adverse childhood experiences (ACE) such as physical or sexual abuse might contribute to those changes. Furthermore, noradrenaline can affect cognitive processes, e.g. learning and memory. Cognitive dysfunctions constitute an important symptom of MDD. We aimed to investigate the relationship of alpha2-receptor dysregulation with learning processes in MDD by conducting a differential fear conditioning paradigm after double-blind administration of the alpha2-receptor antagonist yohimbine versus placebo. To investigate the role of ACE systematically, we included four groups of healthy participants and MDD patients with and without ACE (MDD-/ACE-: N = 44, MDD-/ACE+: N = 26, MDD+/ACE-: N = 24, MDD+/ACE+: N = 24; without antidepressant medication). We found increased noradrenergic activity after yohimbine administration across groups as measured by alpha-amylase and blood pressure. Overall, fear responses were higher after yohimbine as indicated by skin conductance responses and fear-potentiated startle responses. While we found no significant MDD effect, ACE had significant impact on the ability to discriminate between both conditioned stimuli (CS+ predicting an aversive stimulus, CS- predicting none), depending on drug condition. After yohimbine, CS discrimination decreased in individuals without ACE, but not in individuals with ACE. Differences in the response to yohimbine might be explained by aberrant alpha2-receptor regulation in individuals with ACE. Impaired discrimination of threat and safety signals might contribute to enhanced vulnerability following ACE.

Angiotensin involvement in trauma processing-exploring candidate neurocognitive mechanisms of preventing post-traumatic stress symptoms.

The angiotensin-II antagonist losartan is a promising candidate that has enhanced extinction in a post-traumatic stress disorder (PTSD) animal model and was related to reducing PTSD symptom development in humans. Here, we investigate the neurocognitive mechanisms underlying these results, testing the effect of losartan on data-driven and contextual processing of traumatic material, mechanisms proposed to be relevant for PTSD development. In a double-blind between-subject design, 40 healthy participants were randomised to a single oral dose of losartan (50 mg) or placebo, 1 h before being exposed to distressing films as a trauma analogue while heart rate (HR) was measured. Peritraumatic processing was investigated using blurry picture stimuli from the films, which transformed into clear images. Data-driven processing was measured by the level of blurriness at which contents were recognised. Contextual processing was measured as the amount of context information retrieved when describing the pictures' contents. Negative-matched control images were used to test perceptual processing of peripheral trauma-cues. Post-traumatic stress symptoms were assessed via self-report questionnaires after analogue trauma and an intrusion diary completed over 4 days following the experiment. Compared to placebo, losartan facilitated contextual processing and enhanced detail perception in the negative-match pictures. During the films, the losartan group recorded lower HR and higher HR variability, reflecting lower autonomic stress responses. We discuss potential mechanisms of losartan in preventing PTSD symptomatology, including the role of reduced arousal and increased contextual processing during trauma exposure, as well as increased threat-safety differentiation when encountering peripheral trauma-cues in the aftermaths of traumatic events.

Agomelatine treatment corrects impaired sleep-wake cycle and sleep architecture and increases MT1 receptor as well as BDNF expression in the hippocampus during the subjective light phase of rats exposed to chronic constant light.

RATIONALE: Exposure to chronic constant light (CCL) has a detrimental impact on circadian rhythms of motor activity and sleep/wake cycles. Agomelatine is an atypical antidepressant showing a chronotropic activity. OBJECTIVES: In this study, we explored the role of melatonin (MT) receptors and brain-derived neurotrophic factor (BDNF) in the brain in the mechanism underlying the effects of agomelatine on diurnal variations of motor activity, sleep/wake cycle, and sleep architecture in a rat model of CCL. METHODS: In Experiment #1, home cage activity was monitored automatically with cameras for a period of 24 h. The diurnal rhythm of MT1, MT2 receptors, and BDNF expression in the hippocampus and frontal cortex (FC), was tested using the ELISA test. In Experiment #2, rats were equipped with electroencephalographic (EEG) and electromyographic (EMG) electrodes and recordings were made under basal conditions (12:12 LD cycle + vehicle), LL + vehicle and LL + agomelatine (40 mg/kg/day for 21 days). RESULTS: The rats exposed to CCL showed an impaired diurnal rhythm of motor activity and sleep/wake cycle with reduced NREM sleep and delta power and increased REM sleep and theta power. The duration and number of episodes of the wake were diminished during the subjective dark phase in this group. The circadian rhythm of MT1 and MT2 receptors and their expression did not change in the hippocampus and FC under CCL exposure, while the BDNF levels in the hippocampus decreased during the subjective light phase. Agomelatine restored the diurnal rhythm of motor activity, disturbed sleep/wake cycle, and sleep architecture, which effect was accompanied by an increase in MT1 receptor and BDNF expression in the hippocampus at 10:00 in CCL rats. CONCLUSIONS: These findings support the value of agomelatine as an antidepressant that can adjust circadian homeostasis of motor activity and sleep/wake cycle in a CCL model.