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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.

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.

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.

Background Citrus essential oil (EO) has been used for mood elevation and sedative hypnotic purposes. However, scientific proofs of its central nervous system (CNS) action remained largely unexplored. This study investigated chemotypes, electrical brain waves and sleep-wake effects of the essential oil from Citrus reticulata in rat model. Methods Chemical contents of citrus EO were analyzed using gas chromatography-mass spectrometry (GC–MS). Male Wistar rats implanted with electrodes on the frontal and parietal skulls were used for electroencephalographic (EEG) recording while inhaling the citrus EO (200 μl on cotton wool). Diazepam (10 mg/kg, p.o.) was used as a standard anxiolytic drug. EEG frequency analyses were performed by using Fast Fourier transform. All data were statistical analyzed using One-way ANOVA followed by Tukey's test. Results GC–MS analysis reveal d -limonene (95.7%) as a major constituent of citrus EO. The EEG results showed that overall EEG patterns of citrus EO effects were relatively similar to that of diazepam. However, significant differences between treatments were seen from sleep-wake analyses. Diazepam significantly increased episode numbers of awake and non-rapid eye movement (REM) sleep and reduced averaged episode duration. On the other hand, the citrus EO significantly decreased REM sleep latency and increased total time and episode numbers of REM sleep. Conclusion These findings demonstrated unique CNS effects of C. reticulata EO with EEG fingerprints and sleep-wake profiles. The data might be useful for citrus essential oil sub-classification and clinical application.

There is an on-going debate about medicinal use of kratom plant (Mitragyna speciosa (MS)) on whether it has beneficial or adverse effects. This study aimed to examine long-term weight-reducing effects, toxicity, and dopamine pathway activation of MS alkaloid extract on adult male Wistar rats. In anorexic study, the rats were divided into 3 groups (n = 10), receiving intragastric administration once a day for 19 weeks as control (distilled water), chronic (20 mg/kg MS alkaloid extract) and withdrawal (20 mg/kg MS alkaloid extract for week 1-12 and distilled water for week 13-19) groups. Body weights were measured daily, and blood samples were collected at the end of study for biochemical and hematological tests. In immunohistochemistry, the effects of the extract (40 and 80 mg/kg) on the nucleus accumbens (NAc) and striatum (STr) were determined by using Fos-like immunoreactivity. From week 2 to 19, the results showed a significant reduction in body weight gain produced by the extract. Cessation of the treatment at week 12 did not result in a rebound weight gain. Chronic MS alkaloid extract treatment significantly decreased non-fasting blood sugar, triglyceride, uric acid and blood urea nitrogen (BUN). However, elevated SGOT may suggest possible hepatotoxicity. Chronic MS alkaloid extract treatment also produced baseline levels for most of the hematological parameters except a decrease of monocyte. In immunohistochemistry, the acute treatment did not induce Fos-like immunoreactivity in the NAc and STr. These data demonstrated the beneficial effects of the MS alkaloid extract for possible treatment of metabolic syndromes without toxicity and rewarding effect.

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 85.62 $\pm$ 0.29%. 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 79.78 $\pm$ 0.39% and 79.53 $\pm$ 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.

According to European traditional pharmacopeia, as well as in Chinese traditional medicine, watercress (Nasturtium officinale) has a property in enhancing physical stamina during stress condition. The aim of the study was to evaluate the neuroprotective effects of watercress extract (WCE) on dexamethasone-induced neurodegeneration in mice. Swiss albino male mice (35-40 g) were divided into 6 groups: double distilled water (DW) and normal saline solution (NSS) (DW+NSS), DW and dexamethasone (DW+DEX)-treated for 21 days, 80 mg/kg of watercress extract (WCE) and NSS (80WCE+NSS), and WCE-treated (14 days prior to and during dexamethasone treatment) at variable doses of 20 mg/kg (20WCE+DEX), 40 mg/kg (40WCE+DEX), and 80 mg/kg (80WCE+DEX). At the end of the experiment, animals were tested for spatial memory and learning ability by Morris Water Maze apparatus to determine the escape latency time (ELT), and the density of parvalbumin (PV)-immunoreactive (PV-ir) neurons in the hippocampus of the brain, using immunohistochemistry. After dexamethasone treatment, the animals had significantly lower body weight, higher ELT and reduced density of PV-ir neurons in the CA1 and CA2 regions of the hippocampus, compared to the control animals. These parameters partially improved in animals supplemented with WCE but without a dose-related pattern. This study suggests that WCE may be beneficial for neuroprotection in stress-induced neurodegeneration.

The efficacy of pseudoephedrine (PSE) as a nasal decongestant has been well‑demonstrated; however, PSE is strictly prescribed as a control substance due to its controversial psychostimulant effects. Although standard stimulatory drugs increase exploratory behavior and stimulate the dopamine system, the exact effects of PSE on locomotion and electrical activity in the striatum have not been determined. This study aimed to examine and compare the locomotor activities, local field potential (LFP) and sleep‑wake patterns produced by PSE and morphine, which is a standard drug used to promote psychomotor activity. Male Swiss albino mice were anesthetized and implanted with an intracranial electrode into the striatum. Animals were divided into four groups, which received either saline, PSE or morphine. Locomotor activity and LFP signals were continuously monitored following pseudoephedrine or morphine treatment. One‑way ANOVA revealed that locomotor count was significantly increased by morphine, but not PSE. Frequency analyses of LFP signals using fast Fourier transform also revealed significant increases in spectral powers of low‑ and high‑gamma waves following treatment with morphine, but not PSE. Sleep‑wake analysis also confirmed significant increases in waking and decreases in both non‑rapid eye movement and rapid eye movement sleep following morphine treatment. Sleep‑wakefulness did not appear to be disturbed by PSE treatment. These findings indicate that acute PSE administration, even at high doses, does not have psychostimulatory effects and may be relatively safe for the treatment of non‑chronic nasal congestion.

Pueraria mirifica (PM) is a phytoestrogen-rich plant that was tested to establish if its phytosteroids could prevent estrogen dependent sarcopenia. The effect of PM on the estrogen levels, estrous cycle, toxicity, muscle mass, strength and endurance of extensor digitorum longus (EDL) and gastrocnemius muscles of ovariectomized rats was investigated. Adult female Wistar rats were divided into six groups: Sham-operated (SHAM); ovariectomized (OVX) fed with distilled water (PM0); OVX injected with 40 μg/kg estradiol benzoate (E40); (4-6) OVX fed with ethanolic extract of PM at doses of 50 (PM50), 500 (PM500) and 1000 (PM1000) mg/kg for 90 days. After treatment with all three doses of PM, no toxicity was detected to the hematopoietic system and liver function whereas the E40 group did show toxic effects. Treatment with 50 and 500 mg/kg of PM showed no effect on uterine hypertrophy and caused no arrest of the estrous cycle whereas treatment with estrogen and 1000 mg/kg of PM treatment did. The estrogen level, the cross sectional area of the EDL and the gastrocnemius muscle fiber strength and endurance were all significantly reduced in the PM0 group compared to that of the SHAM group (p

Background: Essential oils (EOs) have been claimed to modulate mental functions though the most of data were obtained from subjective methods of assessment. Direct effects of EO on brain function remained largely to be confirmed with scientific proof. This study aimed to demonstrate quantifiable and reproducible effects of commercial vetiver (Vetiveria zizanioides) EO inhalation on sleep-waking and electroencephalogram (EEG) patterns in adult male Wistar rats. The experiments were conducted during November 2013 - February 2014. Materials and Methods: The following electrode implantation on the skull, control, and treated animals were subjected for EEG recording while inhaling water and vetiver EO (20 and 200 µl), respectively. Fast Fourier transform was used for analysis of EEG power spectrum. Results: One-way ANOVA analysis confirmed that vetiver EO inhalation significantly increased total waking and reduced slow-wave sleep time. Moreover, EO inhalation decreased alpha and beta1 activity in both frontal and parietal cortices and increased gamma activity in the frontal cortex. Changes in these frequencies began almost from the start of the inhalation. Conclusion: These data suggest refreshing properties of vetiver EO on electrical brain activity and alertness.

Background Many antidepressants are effective in alleviating ethanol withdrawal symptoms. However, most of them suppress rapid eye movement (REM) sleep. Thus, development of antidepressants without undesirable side effects would be preferable. Previously, crude alkaloid extract from Mitragyna speciosa (MS) Korth was found to produce antidepressant activities. It was hypothesized that the alkaloid extract from MS may attenuate ethanol withdrawal without REM sleep disturbance. Methods Adult male Wistar rats implanted with electrodes over the frontal and parietal cortices were used for two separated studies. For an acute study, 10 mg/kg fluoxetine or 60 mg/kg alkaloid extract from MS were administered intragastrically. Electroencephalographic (EEG) signals were recorded for 3 h to examine sleep profiles and EEG fingerprints. Another set of animal was used for an ethanol withdrawal study. They were rendered dependent on ethanol via a modified liquid diet (MLD) containing ethanol ad libitum for 28 days. On day 29, fluoxetine (10 mg/kg) or alkaloid extract from MS (60 mg/kg) were administered 15 min before the ethanol-containing MLD was replaced with an isocaloric ethanol-free MLD to induced ethanol withdrawal symptoms. Results The sleep analysis revealed that alkaloid extract from MS did not change any REM parameters which included average duration of each REM episode, total REM time, number of REM episode and REM latency whereas fluoxetine significantly suppressed all REM parameters and delayed REM latency. However, power spectral analysis revealed similar fingerprints for fluoxetine and alkaloid extract from MS characterized by decreasing powers in the slow frequency range in frontal and parietal cortical EEG. Neither treatment affected spontaneous motor activity. Finally, both alkaloid extract from MS and fluoxetine were found to significantly attenuate ethanol withdrawal-induced hyperexcitability (increases gamma activity) in both cortices and to reduce locomotor activity. Conclusion The present study demonstrated that the alkaloid extract from MS alleviates ethanol withdrawal severity with no side effect on REM sleep. In addition, these data suggest that suppressive effects on slow frequency powers but not REM sleep may be hallmarks of effective antidepressants for ethanol withdrawal treatment.

Functional role of the striatum in motor control has been widely studied. In addition, its involvement in reward function as a brain area in the dopamine system has also been mentioned. However, neural signaling in the striatum in response to consumption of emotional enhancing substances remained to be explored. This study aimed to investigate local field potential (LFP) of the striatum following morphine administration. Male Swiss albino mice implanted with electrode into the striatum were given an intraperitoneal injection of either saline or morphine (5 or 15 mg/kg). LFP and locomotor activity of individual animals were simultaneously recorded in the recording chamber following the administration. The inspection of LFP tracings revealed the increase in fast wave induced by morphine particularly at a high dose. Statistical analyses were performed using a one way ANOVA followed by Tukey post hoc test. Frequency analysis using Fast Fourier transform also confirmed a significant elevation of low gamma (30-44.9 Hz) activity. When analyzed in time domain, significant increase in low gamma power was observed from the 15th to 65th min following 15 mg/kg morphine treatment. Moreover, morphine treatment also exhibited a stimulating effect on locomotor speed. However, regression analyses revealed no significant correlation between low gamma power and locomotor speed. In summary, this study demonstrated the increase in low gamma oscillation in the striatum and this effect was not associated with locomotor activity of animals. Thus, it is possible that low gamma oscillation induced by morphine treatment is related with the reward function.

The lateral hypothalamus plays an important role in homeostasis. It is sensitive to negative energy balance and believed to interact with other brain regions to mediate food seeking behavior. However, no neural signaling of hunger in the lateral hypothalamus has been studied. Male Swiss albino mice implanted with intracranial electrodes into the lateral hypothalamus and the hippocampus were randomly treated with drinking water for control condition, 18-20 h deprivation of food for hunger condition, and fluid food for satiety condition. Therefore, local field potential (LFP) and locomotor activity of animals were simultaneously recorded. One way ANOVA with Tukey's post hoc test was used for statistical analysis. Frequency analysis of LFP revealed that food deprivation significantly increased the power of gamma oscillation (65-95 Hz) in the lateral hypothalamus and the hippocampus. However, satiety did not change the oscillation in these regions. Moreover, no significant difference among groups was observed for locomotor count and speed. The analysis of coherence values between neural signaling of these two brain areas also confirmed significant increase within a frequency range of 61-92 Hz for hunger. No change in coherence value was induced by satiety. In summary, this study demonstrated neural signaling of the lateral hypothalamus in response to hunger with differential power spectrum of LFP and the interplay with the hippocampus. The data may suggest critical roles of the lateral hypothalamus in detection of negative energy balance and coordination of other higher functions for food related learning or behaviors through the connectivity with the hippocampus.

In the past decade, neural processing has been extensively studied in cognitive neuroscience. However, neural signaling in the nucleus accumbens (NAc) that might clarify reward process remained to be investigated. Male Swiss albino ICR mice implanted with intracranial electrodes into the NAc and the ventral tegmental area (VTA) were used for morphine administration and local field potential (LFP) recording. One-way ANOVA revealed significant increases in low (30.3-44.9 Hz) and high (60.5-95.7 Hz) gamma powers in the NAc following morphine administration (5 and 15 mg/kg, i.p.). These gamma activities oscillated independently with different time-course responses. Locomotor activity was also significantly increased by morphine administration. Regression analyses revealed that high gamma activity induced by morphine was positively correlated with distance travelled by animals. Low and high gamma powers were completely abolished by injection of naloxone, a non-specific opiate antagonist. Analysis of phase-amplitude coupling confirmed that slow oscillations at 1-4 Hz (delta) and 4-8 Hz (theta) for phase were found to significantly increase modulation index of broad (30.27-80.77 Hz) and narrow (59.48-70.34 Hz) frequency ranges for amplitude, respectively. Moreover, significant increases in coherence values between the NAc and the VTA during 30-40 min following morphine administration were seen for 22.46-44.90 Hz frequency range. Altogether, this study demonstrated changes of LFP oscillations in the NAc with low and high gamma activities, delta- and theta-gamma couplings and interplay with VTA in response to morphine administration. These findings represent neural signaling in the mesolimbic dopamine pathway that might process reward function.

Glucocorticoids arising from chronic stress and long-term inflammatory treatment with corticosteroids are both associated with neuropathology and cognitive impairments. Many previous studies have focused on changes in brain morphology and deficits in learning behavior. However, effects of long-term exposure to stress hormones on electrical brain signaling and sleep-wake patterns have remained largely unexplored. This study aimed to monitor electroencephalographic (EEG) patterns induced by prolonged dexamethasone exposure. Adult male Wistar rats implanted with electrodes on the skull over the frontal and parietal cortices were intraperitoneally injected with either saline or dexamethasone (0.5 mg/kg) once daily for 21 consecutive days. Longitudinal EEG recording was performed on day 6, 11, 16 and 21. Fast Fourier transform was used for frequency power analysis. One-way ANOVA revealed significant increases in parietal EEG power of slow frequencies (delta, theta and alpha) particularly, with the dominant theta activity seen as early as day 11 of dexamethasone treatment. Sleep-wake analysis on day 21 confirmed a significant reduction of rapid-eye movement (REM) sleep and increased slow frequency oscillations mainly in the parietal cortex during the awake period. The number of high-voltage spindles (HVSs) (6-10 Hz EEG oscillation) was significantly increased during awake and slow wave sleep (SWS) periods following dexamethasone treatment. These findings demonstrated that distinct frequency oscillations, sleep-wakefulness and sleep spindles may be parameters of neuropathology produced by long-term dexamethasone exposure. Early detection of these parameters might be predictive of neuropathology in long-term corticosteroid users.

Skipjack tuna viscera hydrolysate (TVH) was produced by enzymatic hydrolysis using alcalase. A study of the effect of time and enzyme concentration was performed and formed the basis for preparing TVH with the desired degree of hydrolysis (DH). An enzyme to substrate ratio of 5 g kg−1 (TVH A1) and 16.4 g kg−1 (TVH A2) at pH 8.0 with a temperature of 50 °C, and hydrolysis time of 60 min were found to be optimal conditions to obtain hydrolysis of 42.9% and 62.9%, respectively. Both TVH A1 and TVH A2 were analysed for chemical and amino acid composition and peptide size. The effectiveness of TVH at different DH as feeding attractants was estimated in a feeding trial at different inclusion levels. Ten experimental diets, including a fish meal-based reference diet, were fed to Asian seabass for 28 days. Fish fed the diet supplemented with 30 g kg−1 of TVH A2, and the reference diet showed the highest feed intake (P

Previously, autism spectrum disorder (ASD) has been identified mainly by social communication deficits and behavioral symptoms. However, a link between behaviors and learning process in the brain of animal model of autism remained largely unexplored. Particularly, spontaneous neural signaling in learning-related brain areas has not been studied. This study investigated local field potential (LFP) of the hippocampus (HP), the olfactory bulb (OB) and the medial prefrontal cortex (mPFC) in mice prenatally exposed to valproic acid (VPA) on gestational day 13. Adult male Swiss albino mouse offspring implanted with intracranial electrodes were used. VPA-exposed mice exhibited ASD-associated behaviors. Hippocampal LFP analysis revealed that VPA group significantly increased low gamma activity (25-45 Hz) during awake immobility. Regression analyses confirmed positive correlations between locomotor speed and hippocampal theta oscillations in control but not VPA group. VPA group exhibited increases in delta (1-4 Hz) and beta (25-35 Hz) activities in OB during awake immobility and active exploring, respectively. Moreover, significantly increased and decreased coherences between HP and OB of VPA animals were seen within gamma (active exploration) and theta (awake immobility) ranges, respectively. In addition, significant increase in coherence between HP and mPFC was seen within delta range during active exploration. In addition to three ASD symptoms, VPA animals also exhibited differential patterns of olfacto-hippocampal LFP, altered locomotor speed-related hippocampal theta activities and distinct interplays between HP and learning-related brain areas. The altered olfacto-hippocampal and medial prefrontal cortex-hippocampal networks may underlie impairments in autism mouse model.

In this study, we examined the effects of restricted feeding and of central administration of an orexigenic ghrelin agonist GHRP-6 on peptide mRNA expression in the hypothalamus. We compared rats fed ad libitum with rats that were allowed food for only 2 h every day, and treated with a continuous chronic i.c.v. infusion of GHRP-6 or vehicle. Ad libitum fed rats exposed to GHRP-6 increased their food intake and body weight over 6 days, but, at the end of this period, neuropeptide Y mRNA expression in the arcuate nucleus was not different to that in control rats. By contrast, expression of neuropeptide Y mRNA in the arcuate nucleus was elevated in food-restricted rats, consistent with the interpretation that increased expression reflects increased hunger. However, neuropeptide Y mRNA expression was no greater in food-restricted rats infused with GHRP-6 than in food-restricted rats infused with vehicle; thus if the drive to eat was stronger in rats infused with GHRP-6, this was not reflected by higher levels of neuropeptide Y mRNA expression. Expression of vasopressin mRNA and corticotrophin releasing factor (CRF) mRNA in the paraventricular nucleus (PVN) was not changed by food restriction. GHRP-6 infusion increased CRF mRNA expression in ad libitum rats only.