Sedative and hypnotic effects with cortical EEG sleep-wake profiles of Millingtonia hortensis dried flower aqueous in mice.

The ethnopharmacological relevance of the Millingtonia hortensis (M. hortensis) flower's aqueous extract lies in its traditional use as a herbal remedy in Southeast Asia. With a rich history in folk medicine, this aqueous has been esteemed for its purported sedative and anxiolytic properties. Our research delves into the scientific basis of these traditional claims, exploring the potential mechanisms underlying the observed effects of M. hortensis flower's aqueous extract on sleep promotion and mood regulation. This study aimed to explore the sleep-promoting effects of M. hortensis dried flower in mice, using an aqueous concentration equivalent to a human concentration of 2.7 mg/mL. Anxiolytic and antidepressant properties were evaluated using behavioural tests, while electroencephalography (EEG) analysis probed the neural mechanisms underlying sleep promotion post-consumption. The aqueous extract of M. hortensis dried flower administered to mice showed a decrease in immobility in the forced swimming test, demonstrating antidepressant-like effects. Moreover, mice treated with M. hortensis aqueous exhibited increased non-rapid eye movement (NREM) sleep duration, corroborating sleep-promoting potential. EEG analysis of mice treated with M. hortensis aqueous revealed heightened beta oscillations in the frontal and parietal cortex, while pre-treatment with M. hortensis aqueous or diazepam enhanced rapid eye movement (REM) sleep after thiopental administration. Interestingly, M. hortensis aqueous pre-treatment augmented delta frequency ranges in the frontal cortex. Overall, these findings indicate that M. hortensis dried flower's aqueous extract, at a human-equivalent dosage, exerts significant behavioural and neural effects specifically, sedative and hypnotic aspects in mice, corroborating its potential as a natural remedy to promote sleep and regulate mood.

Changes in Anxiety-Related Behaviors, Voiding Patterns, and Urinary Bladder Contractile Properties in Male Mice Exposed to Water Avoidance Stress for 1 Day and 28 Days.

Repeated water avoidance stress (WAS) for 10 days is a common rodent model to mimic the effect of chronic psychological stress on urinary bladder dysfunction. However, it remains obscure whether changes in the stress exposure period impact urinary bladder impairment differently. Therefore, this study aimed to investigate the effect of 1 (acute), 10 (chronic), and 28 (prolonged) days of WAS on anxiety-related behavior, voiding pattern, urinary bladder mast cells, and bladder contractility in C57BL/6J male mice. Mice exposed to 1 and 10 days of WAS showed decreased unsupported rearing. A decreased total void area after 1 and 10 days of the WAS was observed, which was reversed in the 28-day-WAS group. There was an increased number of degranulated mast cells in the bladder of the 10-day-WAS group. The 1-day WAS exposure enhanced tonic contractile response to a muscarinic agonist, carbachol, which was reversed by 5-HT3 receptor antagonist pre-incubation. Interestingly, the 28-day WAS group showed a similar tonic contractile response to the control group. Our findings provide more insightful information about using 1-day WAS as an acute psychological stress model, and stress exposure longer than 10 days did not produce anxiety-like behavior and urinary bladder impairment.

Estrogen deficiency affects synchronized neural connectivity in the olfactory bulb-nucleus accumbens circuit: A local field potential study in ovariectomized mouse model.

Estrogen plays a crucial role in regulating various brain functions, including cognitive, emotional, and social behaviors. Menopausal women face a decline in estrogen levels, which has been linked to several physical and mental health issues. However, the impact of estrogen on the olfactory bulb-nucleus accumbens (OB-NAc) circuit, which is essential for regulating emotions and cognitive behaviors, remains poorly understood. To test the hypothesis that estrogen deficiency affects signal processing, we recorded local field potentials (LFPs) using intracranial electrodes implanted in four-week-old ovariectomized (OVX) mice during an open-field test (OFT). The results showed a decrease in locomotor activity and increase in anxiety-like behaviors in OVX mice. Furthermore, we found a decrease in high-gamma power in the OB. We analyzed coherence and inter-region phase-amplitude coupling (ir-PAC) to explore the connectivity between the OB and NAc. We observed a decrease in low-gamma and high-gamma coherence in OVX mice. Additionally, we found that the direction of connectivity from the NAc to the OB was disrupted in OVX mice. In summary, our study provides evidence that estrogen deficiency is linked to synchronized neural connectivity changes in the OB-NAc circuit. These findings have implications for our understanding of the roles played by the OB-NAc neural circuit and estrogen in the regulation of general exploratory behavior and anxiety-like behavior.

Complexity measures reveal age-dependent changes in electroencephalogram during working memory task.

The alterations in electroencephalogram (EEG) signals are the complex outputs of functional factors, such as normal physiological aging, pathological process, which results in further cognitive decline. It is not clear that when brain aging initiates, but elderly people are vulnerable to be incipient of neurodegenerative diseases such as Alzheimer's disease. The EEG signals were recorded from 20 healthy middle age and 20 healthy elderly subjects while performing a working memory task. Higuchi's fractal dimension (HFD), Katz's fractal dimension (KFD), sample entropy and three Hjorth parameters were extracted to analyse the complexity of EEG signals. Four machine learning classifiers, multilayer perceptron (MLP), support vector machine (SVM), K-nearest neighbour (KNN), and logistic model tree (LMT) were employed to distinguish the EEG signals of middle age and elderly age groups. HFD, KFD and Hjorth complexity were found significantly correlated with age. MLP achieved the highest overall accuracy of 93.75%. For posterior region, the maximum accuracy of 92.50% was achieved using MLP. Since fractal dimension associated with the complexity of EEG signals, HFD, KFD and Hjorth complexity demonstrated the decreased complexity from middle age to elderly groups. The complexity features appear to be more appropriate indicators of monitoring EEG signal complexity in healthy aging.

Effects of oral administration of ondansetron, a 5-HT3 receptor antagonist, on anxiety-related behaviors and colonic hypercontractility in repeated stress-induced mice.

PURPOSE: Chronic psychological stress develops and exacerbates irritable bowel syndrome (IBS). 5-hydroxytryptamine (5-HT) via activation of intestinal 5-HT3 receptors involves impairment of intestinal functions. This study aimed to investigate the effects of ondansetron, a 5-HT3 receptor antagonist, on locomotor activity, anxiety-related behaviors, and colonic functions in repeated water avoidance stress. MATERIALS AND METHODS: Food intake and fecal pellet output (FPO) of sham stress (SS), water avoidance stress (WS), and water avoidance stress with oral administration of ondansetron (1 mg/kg BW) (WA) groups were monitored along the water avoidance stress protocol for 10 consecutive days. On day 11, locomotor activity and anxiety-related behaviors were determined using an open field test. Contractile properties of colonic tissues in response to KCl and a cumulative dose of carbachol (CCh) were determined using in vitro organ bath technique. RESULTS: FPO was significantly increased in the WS group after 7 days of water avoidance stress, which was reversed in WA group. WS group decreased unsupported rearing behavior compared to WS group, which was not altered in the WA group. The colon of the WS group had a higher tonic contraction in response to CCh than the SS and WA groups, which was reversed with ondansetron pre-incubation. CONCLUSIONS: Oral administration of ondansetron prevented increased FPO but did not affect anxiety-related behavior in repeated stress model. Colonic hypercontractility in the stressed mice was related to increased responses to cholinergic-induced contractions, which involved 5-HT3 receptors. Our findings suggest the modulatory roles of 5-HT3 receptors to mediate stress-induced colonic dysfunction.

Local field potential (LFP) power and phase-amplitude coupling (PAC) changes in the striatum and motor cortex reflect neural mechanisms associated with bradykinesia and rigidity during D2R suppression in an animal model.

Impairments in motor control are the primary feature of Parkinson's disease, which is caused by dopaminergic imbalance in the basal ganglia. Identification of neural biomarkers of dopamine D2 receptor (D2R) suppression would be useful for monitoring the progress of neuropathologies and effects of treatment. Male Swiss albino ICR mice were deeply anesthetized, and electrodes were implanted in the striatum and motor cortex to record local field potential (LFP). Haloperidol (HAL), a D2R antagonist, was administered to induce decreased D2R activity. Following HAL treatment, the mice showed significantly decreased movement velocity in open field test, increased latency to descend in a bar test, and decreased latency to fall in a rotarod test. LFP signals during HAL-induced immobility (open field test) and catalepsy (bar test) were analyzed. Striatal low-gamma (30.3-44.9 Hz) power decreased during immobility periods, but during catalepsy, delta power (1-4 Hz) increased, beta1(13.6-18 Hz) and low-gamma powers decreased, and high-gamma (60.5-95.7 Hz) power increased. Striatal delta-high-gamma phase-amplitude coupling (PAC) was significantly increased during catalepsy but not immobility. In the motor cortex, during HAL-induced immobility, beta1 power significantly increased and low-gamma power decreased, but during HAL-induced catalepsy, low-gamma and beta1 powers decreased and high-gamma power increased. Delta-high-gamma PAC in the motor cortex significantly increased during catalepsy but not during immobility. Altogether, the present study demonstrated changes in delta, beta1 and gamma powers and delta-high-gamma PAC in the striatum and motor cortex in association with D2R suppression. In particular, delta power in the striatum and delta-high-gamma PAC in the striatum and motor cortex appear to represent biomarkers of neural mechanisms associated with bradykinesia and rigidity.

Differential local field potential oscillations in the dorsal striatum and locomotor activity induced by morphine and haloperidol in mice.

Dopamine (DA) depletion in the dorsal striatum underlies symptoms of basal ganglia pathologies, including Parkinson's disease (PD). Various drug compounds are used to enhance DA levels for therapeutic purposes. Understanding neural signaling and movement patterns associated with over­ and under­stimulation of the DA system is essential. This study investigated striatal local field potential (LFP) oscillation and locomotor activity following treatments with morphine, a DA release enhancer, and haloperidol (HAL), a DA D2 receptor (D2R) antagonist in mice. After intracranial electrodes were placed into the dorsal striatum of male Swiss albino ICR mice, intraperitoneal injections of morphine or HAL were administered. LFP signals and spontaneous motor activity were recorded simultaneously. The results showed that morphine significantly increased locomotor speed, both low (30.3-44.9 Hz) and high (60.5-95.7 Hz) LFP gamma powers and delta (1-4 Hz)­gamma (30.3-95.7 Hz) phase­amplitude coupling. In contrast, HAL treatments were found to significantly decrease these parameters. Moreover, regression analyses also revealed significant positive correlations between locomotor speed and high gamma powers. Taken together, these results demonstrate opposite LFP oscillations in the dorsal striatum with low and high gamma activities, and delta­gamma couplings in response to a DA release enhancer and D2R antagonist by morphine and HAL, respectively. These parameters reflect fluctuation of neuronal activity in the dorsal striatum that might be useful for pathological research and drug discovery for PD.

The Decline of Cortical Beta Oscillation on the Function of Eye-hand Coordination in the Healthy Elderly.

BACKGROUND/AIM: There seems to be a correlation between changes in movement patterns with aging and brain activation. In the preparation and execution of movements, neural oscillations play an important role. In this study, cortical high frequency brain oscillations were analyzed in 15 healthy young adults and 15 elderly adults who participated in eye-hand coordination tasks. PATIENTS AND METHODS: The brain activities of healthy young and older adults were recorded using electroencephalography (EEG). RESULTS: Elderly participants spent significantly more time completing the task than young participants. During eye-hand coordination in elderly groups, beta power decreased significantly in the central midline and parietal brain regions. The data suggest that healthy elderly subjects had intact cognitive performance, but relatively poor eye-hand coordination associated with loss of beta brain oscillation in the central midline and parietal cortex and reduced ability to attentional movement. CONCLUSION: Beta frequency in the parietal brain sites may contribute to attentional movement. This could be an important method for monitoring cognitive brain function changes as the brain ages.

ANet: Autoencoder-Based Local Field Potential Feature Extractor for Evaluating an Antidepressant Effect in Mice After Administering Kratom Leaf Extracts.

Kratom (KT) typically exerts antidepressant (AD) effects. However, evaluating which form of KT extracts possesses AD properties similar to the standard AD fluoxetine (flu) remained challenging. Here, we adopted an autoencoder (AE)-based anomaly detector called ANet to measure the similarity of mice's local field potential (LFP) features that responded to KT leave extracts and AD flu. The features that responded to KT syrup had the highest similarity to those that responded to the AD flu at 87.11 ± 0.25%. This finding presents the higher feasibility of using KT syrup as an alternative substance for depressant therapy than KT alkaloids and KT aqueous, which are the other candidates in this study. Apart from the similarity measurement, we utilized ANet as a multi-task AE and evaluated the performance in discriminating multi-class LFP responses corresponding to the effect of different KT extracts and AD flu simultaneously. Furthermore, we visualized learned latent features among LFP responses qualitatively and quantitatively as t-SNE projection and maximum mean discrepancy distance, respectively. The classification results reported the accuracy and F1-score of 90.11 ± 0.11% and 90.08 ± 0.00%. In summary, the outcomes of this research might help therapeutic design devices for an alternative substance profile evaluation, such as Kratom-based form, in real-world applications.

Age-related Deterioration of Alpha Power in Cortical Areas Slowing Motor Command Formation in Healthy Elderly Subjects.

BACKGROUND/AIM: The same neural processes may govern older people's motor and cognitive abilities since an inability to switch between actions develops with aging. In this study, a dexterity test was used to measure motor and cognitive perseverance, which required participants to move their fingers fast and correctly on hole boards. MATERIALS AND METHODS: An electroencephalography (EEG) recording was used to evaluate how healthy young and older adults process brain signals when performing the test. RESULTS: A significant difference was found between the young and older groups in the average time taken to complete the test, with the older group taking 87.4 s and the young group taking 55.21 s. During motor movement, young participants showed alpha desynchronization over the cortex (Fz, Cz, Oz, Pz, T5, T6, P3, P4) in comparison to the resting state. However, compared to the younger group, no alpha desynchronization was found in the aging group during motor performance. It was noteworthy that alpha power (Pz, P3, and P4) in the parietal cortex was significantly lower in older compared to young adults. CONCLUSION: Age-related slowdown in motor performance may be caused by deteriorating alpha activity in the parietal cortex, which functions as a sensorimotor interface. This study provides new insights into how perception and action are distributed between brain regions.

Dopamine Improves Low Gamma Activities in the Dorsal Striatum of Haloperidol-induced Motor Impairment Mice.

BACKGROUND/AIM: The dorsal striatum is a brain area integrating information for movement output. The local field potentials (LFPs) reflect the neuronal activity that can be used for monitoring brain activities and controlling movement. MATERIALS AND METHODS: Rhythmic low gamma power activity (30.1-45 Hz) in the dorsal striatum was monitored according to voluntary motor movement in rotarod and bar tests in 0.5 mg/kg haloperidol-induced mice. RESULTS: Haloperidol can effectively induce movement impairment indicated by decreased low gamma LFP with the lessened rotarod test's latency fall, and the enhanced bar test's descending latency. L-DOPA was used for the induction of a dopamine-dependent signal. The results showed that 25 mg/kg of L-DOPA could reverse the effect of haloperidol by enhancing low gamma oscillation concomitantly with the improvement in behavioral movement as fast as 60 min after administration, suggesting that dopamine signaling increases low gamma frequency of LFP in correlation with the improved mice movement. This work supports quantitative LFP assessment as a monitoring tool to track drug action on the nervous system. CONCLUSION: In animal models of motor impairment, oral dopaminergic treatment can be effective in restoring motor dysfunction by stimulating low gamma power activity in the dorsal striatum.

A 1:1 ratio of cannabidiol: tetrahydrocannabinol attenuates methamphetamine conditioned place preference in mice: A prospective study of antidopaminergic mechanism.

A 1:1 ratio of cannabidiol to tetrahydrocannabinol (CT) was suggested to be safer for therapeutic purposes in many illnesses. However, CT effects on methamphetamine (METH) conditioned place preference (CPP) remained largely unexplored. This study aimed to examine the effects of CT on METH CPP mice evaluated by animal behaviors accompanied by local field potential (LFP) signals analysis. Male ICR mice were implanted with the LFP electrode in the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Animals were next subjected to induce METH CPP by peritoneal injection with 1 mg/kg METH and 0.9 % NaCl on an alternate day for ten sessions and confined to the corresponding compartment for 30 min meanwhile control mice were given normal saline all day for both compartments. On testing day, either 10 mg/kg CT or 20 mg/kg bupropion (BP), a dopamine reuptake inhibitor, and VTA GABAergic suppressor were orally administered before CPP testing. The results revealed that CPP scores elevation was observed in the METH+vehicle and METH+BP mice, but this was reversed by CT treatment. Although both METH+vehicle and METH+BP enhanced the VTA delta power, NAc gamma I power, NAc delta-gamma coupling, and VTA-NAc gamma I coherence, changes in opposite trends of all mentioned parameters were seen by CT application. These improvements were postulated to involve the antidopaminergic effects of CT via modulations of neural signaling in the VTA and NAc. Altogether, the evidence-based study may suggest the use of CT as alternative drug for METH-seeking and craving therapy.

5-HT3 receptors modulate changes in voiding pattern and bladder contractility in water avoidance stress-induced bladder overactivity in male mice.

PURPOSE: Chronic psychological stress aggravates painful bladder syndrome symptoms. Previous studies suggest roles of 5-HT3 receptors in regulating micturition and bladder hypersensitivity. This study aimed to investigate the roles of 5-HT3 receptors in modulating voiding patterns and spontaneous bladder contractile properties in water avoidance stress-induced mice. MATERIALS AND METHODS: Voiding patterns in sham stress (SS), water avoidance stress (WS), and water avoidance stress with daily oral gavage of ondansetron (1 mg/kg BW) (WA) groups were analyzed after exposure to repeated water avoidance stress for 10 days. Changes in contractile activity of isolated bladder in response to KCl, carbachol, and 5-hydroxytryptamine were determined. Bladder mast cell quantification was examined using toluidine blue staining. RESULTS: Urine voided area was significantly decreased in WS group after exposure to 10 days of the stress protocol, which was reversed in the WA group. The WS group had a higher number of urine spots than the SS group. Increased mast cell degranulation was observed in the stressed mice. Bladder strips of the WS group showed higher tonic and amplitude of spontaneous contraction than the SS group, which were normalized by ondansetron administration. Increased response to carbachol-induced bladder contraction was observed in the bladder of stressed mice, which was attenuated with ondansetron pre-incubation. CONCLUSIONS: Water avoidance stress-induced mice exhibited changes in voiding pattern, which was reversed by oral administration with a 5-HT3 receptor antagonist (ondansetron). Enhanced contractile response to cholinergic stimulation in the urinary bladder of the psychological stress-induced bladder overactivity was mediated through 5-HT3 receptors.

Exploring of cardiac autonomic activity with heart rate variability in long-term kratom (Mitragyna speciosa Korth.) users: a preliminary study.

Background: Kratom is a psychoactive plant used to enhance productivity among laborers in Southeast Asian countries. Previous findings from in vitro research of mitragynine, a major component of kratom, suggested a possible risk of heart function abnormality. However, the cardiac autonomic function in long-term kratom users with chewing forms has never been studied. This study aimed to investigate heart rate variability (HRV) indices of cardiac autonomic function in long-term kratom chewers (LKC), compared to the control levels, and also to examine the correlation between HRV indices and relevant kratom use factors. Method: A total number of 50 participants consisted of LKC (n = 31) who regularly chewed fresh kratom leaves for at least 2 years and demographically matched control subjects (n = 19). Resting electrocardiogram (ECG) signals were recorded from subjects for 3 min to analyze the ultrashort HRV in the frequency domain. The normalized low frequency (LFn) and high frequency (HFn) were chosen to be the HRV indices to evaluate cardiac autonomic function. The comparison of HRV indices between groups and the correlation between HRV indices and duration and quantity of kratom use was further conducted in statistical analysis. Results: The LKC significantly increased LFn together with enhanced HFn compared to the control group tested, indicating that LKC changed cardiac autonomic function with parasympathetic dominance. Furthermore, no significant correlation between the HRV indices and the duration and quantity of kratom use was found, suggesting that the HRV indices were not relevant to these factors. The present study provided scientific-based evidence of cardiac autonomic modulation in long-term kratom chewers. LFn and HFn may be promising cardiac autonomic indicators for monitoring health outcomes in LKC.

Neural signaling of methamphetamine craving and seeking intensified by bupropion in the ventral tegmental area-cortico-accumbens circuitry in mice.

Previously, bupropion (BUP), a norepinephrine (NE)/dopamine (DA) transporter blocker and nicotinic acetylcholine receptors (nAChRs) antagonist, was found to intensify methamphetamine (METH) craving behaviours in mice. Intense craving causes relapse in drug dependence. This study characterized local field potential (LFP) patterns in the brain regions associated with METH-conditioned place preference (CPP) enhanced by BUP. Male Swiss albino ICR mice were implanted with LFP electrodes to the ventral tegmental area (VTA), medial prefrontal cortex (mPFC) and the nucleus accumbens core (NAcc). Animals received sessions to learn the association between injection effects (1 mg/kg METH and normal saline) with contextual environments (METH- and saline-paired compartments) during the conditioning phase. A total of 20 mg/kg BUP was given to animals before LFP, and behaviour recording in the CPP apparatus during the post-conditioning phase. The results showed that increased CPP scores and % number of entries to the METH-paired zone, as well as changes in VTA, mPFC and NAcc spectral powers and coherence among these areas, were associated with METH-CPP. Treatment with BUP increased VTA delta and gamma I, decreased mPFC alpha, increased NAcc gamma I and decreased gamma II powers. Coherence analyses revealed that BUP decreased gamma II VTA-mPFC and increased beta and gamma I VTA-NAcc connectivity. Altogether, BUP produced additional effects to that of METH-CPP alone. These findings demonstrated changes in neural circuit activities associated with METH-CPP intensified by BUP. Moreover, modulation of NE/DA systems and/or nAChRs actions in the VTA-cortico-accumbens loop might underlie METH craving and dependence.

Ameliorative effects of alkaloid extract from Mitragyna speciosa (Korth.) Havil. Leaves on methamphetamine conditioned place preference in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) Havil., popularly known as Kratom (KT), is a medicinal plant used for pain suppression in Southeast Asia. It has been claimed to assist drug users withdraw from methamphetamine (METH) dependence. However, its use was controversial and not approved yet. AIM OF THE STUDY: This study was conducted to characterize local field potential (LFP) patterns in the nucleus accumbens (NAc) and the hippocampus (HP) in mice with METH conditioned place preference (CPP) that were treated with KT alkaloid extract. MATERIALS AND METHODS: Male Swiss albino ICR mice were implanted with intracraneal electrodes into the NAc and HP. To induce METH CPP, animals were injected intraperitoneally once a day with METH (1 mg/kg) and saline (0.9% w/v) alternately and put into METH/saline compartments to experience the associations between drug/saline injection and the unique environmental contexts for 10 sessions. Control group received saline injection paired with both saline/saline compartments. On post-conditioning day, effects of 40 (KT40), 80 (KT80) mg/kg KT alkaloid extract and 20 mg/kg bupropion (BP) on CPP scores and LFP powers and NAc-HP coherence were tested. RESULTS: Two-way ANOVA revealed significant induction of CPP by METH sessions (P < 0.01). Multiple comparisons indicated that METH CPP was completely abolished by KT80 (P < 0.001). NAc gamma I (30.0-44.9 Hz) and HP delta (1.0-3.9 Hz) powers were significantly increased in mice with METH CPP (P < 0.01). The elevated NAc gamma I was significantly suppressed by KT80 (P < 0.05) and the increased HP delta was significantly reversed by KT40 (P < 0.01) and KT80 (P < 0.001). In addition, NAc-HP coherence was also significantly increased in gamma I (30.0-44.9 Hz) frequency range (P < 0.05) but it was reversed by KT80 (P < 0.05). Treatment with BP did not produce significant effect on these parameters. CONCLUSIONS: These findings demonstrated that KT alkaloid extract significantly reversed CPP scores and LFP patterns induced by METH administration. The ameliorative effects of the extract might be beneficial for treatment of METH craving and addiction.

Locomotor activity and resting local field potential oscillatory rhythms of 6-OHDA mouse model of Parkinson's disease in response to acute and repeated treatments with L-dopa.

Phase-amplitude coupling (PAC) of local field potential (LFP) has been recognized as higher-order representation of brain states. Neuronal loss in the striatum leads to Parkinson's disease (PD) symptoms and modifies LFP oscillation. However, PAC in the striatum of PD mouse model induced by 6-hydroxydopamne (6-OHDA) remained to be investigated. Male Swiss albino ICR mice were implanted with intracranial electrode and injected with 6-OHDA to the left striatum. Levodopa (L-dopa) (10 mg/kg, oral) was used for treatment once a day from day 15-19. Locomotor activity and resting LFP signals were selectively analyzed on day 15 and 19. One-way ANOVA revealed significant decreases in travelled distance induced by 6-OHDA on both days (p ≤ 0.05). However, the decreased travelled distances were significantly reversed by L-dopa. On day 15, LFP powers of theta, alpha, beta and low gamma waves were significantly increased by 6-OHDA injection and the powers of beta and low gamma were significantly reversed to control level by treatment with L-dopa. On day 19, LFP powers of delta, theta, alpha, beta and low gamma waves were significantly increased by 6-OHDA injection and the powers of low gamma were significantly reversed to control level by treatment with L-dopa. Theta-gamma PAC analyses also confirmed significant increase in modulation index (MI) induced by 6-OHDA on day 19. However, L-dopa failed to significantly reverse the MI to control level. These findings indicated theta-gamma coupling in the striatum of PD mouse model. Taken together, change in striatal theta-gamma PAC might be one of biomarkers in addition to hypokinesia and increased LFP powers that reflect disrupted neural mechanisms in PD mouse model.

Spectral power and theta-gamma coupling in the basolateral amygdala related with methamphetamine conditioned place preference in mice.

The basolateral amygdala (BLA) plays a crucial role in conditioned place preference (CPP) for addictive drugs. However, neural signaling associated with methamphetamine (METH) craving and seeking remained to be investigated. This study characterized local field potential (LFP) oscillatory patterns in the BLA and conditioned place preference induced by METH-related context. Male Swiss albino ICR mice were deeply anesthetized for LFP intracranial electrode implantation in the BLA. Control and METH groups received sessions to learn to associate saline-paired and METH-paired compartments of the CPP apparatus with saline and METH injections, respectively, for 10 days. LFP signals and exploring behavior were recorded simultaneously during pre- and post-conditioning phases. Time spent in METH-paired compartment was normalized and expressed as CPP scores. Fast Fourier Transform (FFT) algorithm was used to analyze LFP powers of 8 discrete frequency ranges (delta, theta, alpha, beta, gamma I-IV). During post-conditioning phase of METH CPP with METH cues, statistical analysis revealed that METH group significantly increased time spent in METH-paired compartment. Significant suppressions of theta and alpha powers were observed. Phase-amplitude cross frequency coupling analyses confirmed significant increases in maximal modulation index (MI), frequency for phase of slow wave and MI of theta-gamma II coupling. Taken together, LFP oscillation in the BLA was sensitive in association with METH CPP. These research findings might suggest the underlying mechanisms of drug reward learning and adaptive changes in the BLA in acquisition of METH CPP and dependence.

Characterization of pharmaco-EEG fingerprint and sleep-wake profiles of Lavandula angustifolia Mill. essential oil inhalation and diazepam administration in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Lavandula angustifolia Mill. Essential oil (Lavender EO) has a long history of medicinal use and is particularly claimed to possess anxiolytic and sedative properties. Lavender EO aromatherapy has been used to reduce distress and improve insomnia naturally. Increasing evidence appeared to show similarities between the effects of lavender EO and the anxiolytic drugs, benzodiazepines. However, its effects on sleep-wake and electrical brain patterns in comparison to that of the standard anxiolytic, diazepam, remained to be explored. AIM OF THE STUDY: The aim of this work was to investigate electroencephalography (EEG) profiles and sleep-pattern elicited by lavender EO inhalation compared to that of diazepam, a standard anxiolytic drug in in vivo rat model. MATERIALS AND METHODS: Adult male Wistar rats were anesthetized for electrode implantation on the frontal and parietal skulls. EEG signals were recorded for 180 min following intraperitoneal injection of diazepam (10 mg/kg) or during continuous inhalation of lavender EO (200 µL) or distilled water (control). Fast Fourier transform was used for the analyses of EEG power spectra and sleep-wake parameters. RESULTS: During a 30-60 min period, diazepam and lavender EO significantly increased frontal powers of 0.78-45.31 and 7.03-18.36 Hz, respectively. Both treatments also increased parietal powers with lower magnitudes of significant change. Significant increases in some frequency ranges remained until a 60-90 min period. Sleep-wake analyses also revealed that diazepam significantly reduced time spent in wake, increased time spent in non-rapid eye movement (NREM), increased episode duration of NREM, decreased numbers of wake episode and decreased rapid eye movement (REM) sleep latency. On the other hand, lavender EO only significantly decreased wake episodes and latency to REM sleep. Lavender EO inhalation reduced numbers of wake episode but maintain normal time spent in wake, NREM and REM sleeps. CONCLUSIONS: These findings might suggest beneficial and distinct anxiolytic-like effects of lavender EO for sleep enhancing purposes.

Adaptive changes in local field potential oscillation associated with morphine conditioned place preference in mice.

Neural adaptation associated with formation of morphine conditioned place preference remained largely unexplored. This study monitored longitudinal changes in neural signaling during pre-conditioning, conditioning and post-conditioning periods of morphine conditioned place preference (CPP) paradigm for investigation of adaptive mechanisms of opiate addiction. Male Swiss albino mice implanted with intracranial electrodes into the nucleus accumbens (NAc), striatum (STr) and hippocampus (HC) were used for recording of local field potentials (LFPs). Animals received a 10-day schedule for associative learning to pair the specific compartment of the chamber with morphine effects. Exploratory behavior and LFP signals were recorded during pre-conditioning (baseline level), conditioning (day 1, 5 and 10) and post-conditioning (day 1, 4 and 7) periods. Repeated measures one-way ANOVA followed by Tukey test revealed significant increases in number of visit and time spent in morphine compartment during post-conditioning days. Frequency analysis of LFP highlighted the increases in alpha activity (12 - 18 Hz) in the NAc from post-conditioning day 1 until day 7. Moreover, significantly increased coherent activities between the pair of NAc-HC were developed within gamma frequency range (35 - 42 Hz) on morphine conditioning day 10 and disappeared during post-conditioning days. Taken together, these findings emphasized NAc LFP signaling and neural connectivities between the NAc and HC associated with morphine CPP. These adaptive changes might underlie the formation of morphine conditioned place preference and behavioral consequences such as craving and relapse.