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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 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.

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.

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 is a psychoactive plant used to enhance productivity among laborers in Southeast Asian countries. Previous findings fromA total number of 50 participants consisted of LKC (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.

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.

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.

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.

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.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.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.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.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.

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.

Songklanakarin Journal of Science an Technology (SJST), 43, 6, 1807-1814

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.

Emerging studies have reported that functional brain networks change with increasing age. Graph theory is applied to understand the age-related differences in brain behavior and function, and functional connectivity between the regions is examined using electroencephalography (EEG). The effect of normal aging on functional networks and inter-regional synchronization during the working memory (WM) state is not well known. In this study, we applied graph theory to investigate the effect of aging on network topology in a resting state and during performing a visual WM task to classify aging EEG signals. We recorded EEGs from 20 healthy middle-aged and 20 healthy elderly subjects with their eyes open, eyes closed, and during a visual WM task. EEG signals were used to construct the functional network; nodes are represented by EEG electrodes; and edges denote the functional connectivity. Graph theory matrices including global efficiency, local efficiency, clustering coefficient, characteristic path length, node strength, node betweenness centrality, and assortativity were calculated to analyze the networks. We applied the three classifiers of K-nearest neighbor (KNN), a support vector machine (SVM), and random forest (RF) to classify both groups. The analyses showed the significantly reduced network topology features in the elderly group. Local efficiency, global efficiency, and clustering coefficient were significantly lower in the elderly group with the eyes-open, eyes-closed, and visual WM task states. KNN achieved its highest accuracy of 98.89% during the visual WM task and depicted better classification performance than other classifiers. Our analysis of functional network connectivity and topological characteristics can be used as an appropriate technique to explore normal age-related changes in the human brain.

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.

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

Ethnopharmacological relevance Mitragyna speciosa (Korth.) Havil. ( M. speciosa ) is among the most well-known plants used in ethnic practice of Southeast Asia. It has gained increasing attention as a plant with potential to substitute morphine in addiction treatment program. However, its action on the central nervous system is controversial. Aim of the study This study investigated the effects of M. speciosa alkaloid extract on naloxone-precipitated morphine withdrawal and neural signaling in the nucleus accumbens (NAc, brain reward center) of mice. Materials and methods The effects of M. speciosa alkaloid extract and mitragynine, a pure major constituent, on naloxone-precipitated morphine withdrawal were examined. Male Swiss Albino (ICR) mice were rendered dependent on morphine before injection with naloxone, a nonspecific opioid antagonist, to induce morphine withdrawal symptoms. The intensity of naloxone-precipitated morphine withdrawal was assessed from jumping behavior and diarrhea induced during a period of morphine withdrawal. To test possible addictive effect of M. speciosa alkaloid extract, mice were implanted with intracranial electrode into the NAc for local field potential (LFP) recording. Following M. speciosa alkaloid extract (80 mg/kg) and morphine (15 mg/kg) treatment, LFP power spectra and spontaneous motor activity were analyzed in comparison to control levels. Results One-way ANOVA and multiple comparisons revealed that M. speciosa alkaloid extract (80 and 100 mg/kg) significantly decreased the number of jumping behavior induced by morphine withdrawal whereas mitragynine did not. Additionally, M. speciosa alkaloid extract significantly decreased dry and wet fecal excretions induced by morphine withdrawal. LFP analysis revealed that morphine significantly decreased alpha (9.7–12 Hz) and increased low gamma (30.3–44.9 Hz) and high gamma (60.5–95.7 Hz) powers in the NAc whereas M. speciosa alkaloid extract did not. Spontaneous motor activity was significantly increased by morphine but not M. speciosa alkaloid extract. Conclusions Taken together, M. speciosa alkaloid extract, but not mitragynine, attenuated the severity of naloxone-precipitated morphine withdrawal symptoms. Neural signaling in the NAc and spontaneous motor activity were sensitive to morphine but not M. speciosa alkaloid extract. Therefore, treatment with the M. speciosa alkaloid extract may be useful for opiate addiction treatment program.

Eating motivation is induced not only by negative energy balance but also food related cues. However, neural processing for acquisition of learned food preference remains to be established. This study aimed to identify hippocampal neural signaling in response to olfactory cue (chocolate scent) after completion of repetitive chocolate sessions. Male Swiss albino mice implanted with intracranial electrode into the hippocampus were used for local field potential (LFP) recording. Animals were given chocolate sessions (a piece of 2g chocolate per each mouse to eat on day 1, 3, 5 and 7). Hippocampal CA1 LFP signals and exploratory behavior of animals receiving chocolate scent were analyzed before and after chocolate sessions. The experiment was performed in a place preference-like apparatus with the zones of normal food pellet and chocolate (both kept in a small perforated cup for smell dispersion) at the opposite ends. Following chocolate sessions, time spent in a chocolate zone and CA1 LFP patterns were analyzed in comparison to control levels. Two-way ANOVA revealed significant increase in time spent seeking for chocolate. Frequency analysis of LFP power spectra revealed significant increases in delta and theta powers. Phase-amplitude analysis showed significant increase in maximal modulation index and decrease in frequency for phase of theta-high gamma coupling. Taken together, neural signaling in the hippocampus was sensitive to chocolate olfactory cue that might underlie learning process in response to repeated chocolate consumptions that primed intense food approaching behavior. Ultimately, these LFP patterns might reflect motivation to eat and predict feeding probability.

Previously, satiated animals or human subjects can still be motivated to eat by palatable food-associated cues. However, neural circuitries of hedonic hunger have not been well investigated. This study identified neural network connectivities between major brain areas in response to chocolate-associated cues following repeated exposures to chocolate. Adult male Swiss albino ICR mice were anesthetized and implanted with intracranial electrodes in the lateral hypothalamus (LHa), nucleus accumbens (NAc), olfactory bulb (OB) and hippocampus (HP) for local field potential (LFP) recording. LFP oscillations were recorded before and after repeated exposures to chocolate for chocolate experienced group whereas control group was not exposed to chocolate. On testing days, satiated animals were individually put into a place preference-like apparatus with two opposite chambers of chocolate and normal chow scent cues, separately. The results showed that chocolate experienced group significantly increased time spent in chocolate chamber whereas control group did not. One-way ANOVA revealed significant influence of chocolate sessions on LFP spectral powers of multiple frequencies in the LHa (delta, low gamma and high gamma) and NAc (high gamma). Moreover, coherence function analyses also highlighted significant increases in LHa-NAc and LHa-OB, and decrease in LHa-HP coherent activities in response to olfactory cues of chocolate. This study demonstrated modifications of neural network connectivity and associative learning following multiple exposures to palatable food. These findings might explain why energy homeostatic hunger is overridden by hedonic hunger.

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.

Food deprivation is known to trigger hunger sensation and motivation to eat for energy replenishing. However, brain mechanisms associated with hunger and neural circuitries that mediate hunger driven responses remained to be investigated. To understand neural signaling of hunger, local field potentials (LFPs) in the lateral hypothalamus (LHa), nucleus accumbens (NAc), dorsal hippocampus (HP) and olfactory bulb (OB) and their interconnectivities were studied in freely moving adult male Albino mice during 18–20 h food deprivation and fed periods. Raw LFP signals were recorded and analyzed for mean values of spectral frequency power and coherence values. One-way repeated measures ANOVA revealed significant increases in spectral powers of beta and gamma frequency ranges induced by food deprivation in the LHa, HP, NAc but not OB. No change of spectral power in these brain regions was induced by food feeding. The analyses of coherent activity between brain regions also deliniated some distributed neural network activities correlated with hunger. In particular, coherent function indicated the increased beta and gamma phase synchrony between the pairs of LHa-HP and NAc-OB regions, and decreased gamma synchrony between the pairs of LHa-NAc and NAc-HP induced by food deprivation. It was found that plasma glucose level, locomotor count, travelled distance and time spent on moving were not altered by food deprivation. These results suggest that changes in LFP hallmarks in these brain regions were associated with hunger driven by negative energy balance.

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.

Valproic acid (VPA) mouse model of autism spectrum disorder (ASD) has been characterized mostly by impaired ultrasonic vocalization, poor sociability and increased repetitive self-grooming behavior. However, its neural signaling remained unknown. This study investigated the local field potentials (LFPs) in the dorsal hippocampal CA1 and the olfactory bulb while animals exploring a novel open field. VPA was administered at gestational day 13. The results demonstrated three core features of ASD in male offspring. However, there was no difference in Y-maze performance and locomotor activity. Analysis of hippocampal LFP power revealed significantly increased slow wave (1-4 Hz) and high gamma (80-140 Hz) oscillations and decreased theta (4-12 Hz) activity in VPA mice. In the olfactory bulb, VPA animals showed greater slow wave (1-4 Hz) and beta (25-40 Hz) activity and lower activity of low gamma (55-80 Hz) wave. Regression analysis revealed positive correlations between hippocampal theta power and locomotor speed for both control and VPA-exposed mice. There was no significant difference between groups for modulation index of theta (4-12 Hz) phase modulated gamma (30-200 Hz) amplitude. These findings characterized VPA mouse model with LFP oscillations that might provide better understanding of neural processing in ASD.

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.

Long term exposure to dexamethasone (Dx) is associated with brain damage especially in the hippocampus via the oxidative stress pathway. Previously, an ethanolic extract from Curcuma longa Linn. (CL) containing the curcumin constituent has been reported to produce antioxidant effects. However, its neuroprotective property on brain histology has remained unexplored. This study has examined the effects of a CL extract on the densities of cresyl violet positive neurons and glial fibrillary acidic protein immunoreactive (GFAP-ir) astrocytes in the hippocampus of Dx treated male rats. It showed that 21days of Dx treatment (0.5 mg/kg, i.p. once daily) significantly reduced the densities of cresyl violet positive neurons in the sub-areas CA1, CA3 and the dentate gyrus, but not in the CA2 area. However, CL pretreatment (100 mg/kg, p.o.) was found to significantly restore neuronal densities in the CA1 and dentate gyrus. In addition, Dx treatment also significantly decreased the densities of the GFAP-ir astrocytes in the sub-areas CA1, CA3 and the dentate gyrus. However, CL pretreatment (100 mg/kg, p.o.) failed to protect the loss of astrocytes in these sub-areas. These findings confirm the neuroprotective effects of the CL extract and indicate that the cause of astrocyte loss might be partially reduced by a non-oxidative mechanism. Moreover, the detection of neuronal and glial densities was suitable method to study brain damage and the effects of treatment.

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.

Administration of the aqueous extract of Mitragyna speciosa at a dose of 300 mg/kg significantly inhibited ethanol withdrawal-induced behaviors that included rearing, displacement and head weaving. The results also showed that at doses of 100, 300 and 500 mg/kg M. speciosa showed antidepressant activity without effect on the spontaneous motor activity.

Systemic or central administration of growth-hormone secretagogues (GHS) induces dense Fos expression in the arcuate nucleus but little or no Fos expression in the ventromedial hypothalamic nucleus, although both sites show intense expression of mRNA for the GHS receptor. Here, we recorded the electrical activity of single neurons from the arcuate nucleus and from the ventromedial hypothalamic nucleus in a rat hypothalamic slice preparation, and compared responses of these two populations to GHS. At both sites, the predominant neuronal response to GHS was a long-lasting excitation, indicating that GHS receptors at both sites are functional and similarly coupled to electrical excitation. We also tested neurons at both sites for their responses to neuropeptide Y and to somatostatin; at both sites the predominant response to each of these peptides was inhibitory. The arcuate cells that are activated by GHS include neuropeptide Y cells and growth hormone-releasing hormone cells. It seems possible that neuropeptide Y released in the ventromedial hypothalamus from the terminals of arcuate neurons counteracts the activation of ventromedial hypothalamic neurons by GHS in vivo, or that somatostatin released following liberation of growth hormone may do so.

Muscle weakness is common during menopause. Effective estrogen replacement was hypothesized to prevent sarcopenia. This study aimed to investigate the estrogen level, estrogen receptors (α and β) immunoreactivities, muscle mass and functions, and parvalbumin (PV) levels in the extensor digitorum longus (EDL) and the gastrocnemius muscles of ovariectomized rats. Adult female Wistar rats (12 weeks old) were divided into five groups: sham-operated (SHAM), and ovariectomized (E0) groups that received 10 weeks of estrogen replacements of 0 μg/kg (E0), 10 μg/kg (E10), 20 μg/kg (E20) and 40 μg/kg (E40). The estrogen levels, ER α and ER β immunoreactivities, muscle fiber sizes and contractivities and the PV levels were reduced in the E0 group, but increased in all the estrogen replacement groups in both muscles. This study indicated that the reduction of estrogen levels led to a decrease of both ER α and ER β resulting in a decline in muscle mass and PV levels. The decrease of PV levels affected muscle performance, whereas estrogen replacement increased both the ER α and ER β. The increase in the PV levels may result in an improvement of muscle performance. This may explain one mechanism of estrogen on muscle mass and strength in estrogen dependent sarcopenia.

Antidepressants have been used for treatment of ethanol withdrawal symptoms mainly in observational studies. However, cortical frequency oscillation of ethanol withdrawal treatment with antidepressants remained to be elucidated. This study aimed to identify surrogate biomarkers that represent intact biological or ethanol withdrawal processes and response to pretreatment with fluoxetine, a selective serotonin reuptake inhibitor, with quantitative methods. Adult male Wistar rats implanted with electrodes over the frontal and parietal cortices were rendered dependent on ethanol via modified liquid diet (MLD) containing ethanol. Then, ethanol-containing MLD was replaced with isocaloric ethanol-free MLD to induce ethanol withdrawal symptoms. Locomotor activity, sleep-wakefulness and spectral frequencies of electroencephalographic (EEG) pattern during ethanol-withdrawal period were analyzed. One-way ANOVA confirmed significant increases in locomotor activity and time spent in awake state and decreases time spent in non-rapid eye movement (NREM) sleep and REM-sleep during ethanol withdrawal period. Fast Fourier Transformation also revealed predominant increases in gamma spectral powers within both the frontal and parietal cortices during ethanol withdrawal. However, these changes, except sleep-wake disturbances, were significantly attenuated by fluoxetine pretreatment (10 mg/kg). The present study supports the hypothesis that serotonergic hypofunction may underlie most of ethanol withdrawal symptoms and proposes that electroencephalographic patterns are valid biomarkers for ethanol withdrawal evaluation and treatment.

In this paper, we aimed to develop a simple technique to classify brain states of rats, including Active, Inactive, REM, and NREM. Two EEG signals (from frontal and parietal cortices) were recorded to create EEG spectrums. The EEG spectrums created by Fast Fourier Transform (FFT) were separated into two sets; training set for the brain state model creation and testing set for experiment. The training set of each brain states which are manually classified as one of four possible brain state models by medical experts was created in terms of spectral mean and standard deviation. A basic method measuring similarity between testing and brain state model spectrums was based on normal distribution model. The results showed that the best classification of our proposed technique was found in NREM state with 95.86%. However, the classification result of inactive state was 73.33%, and overall average accuracy of all brain states was 87.76%.

The pathology of brain atrophy mediated by alcohol was investigated in all parts of the cerebral cortex (the frontal, parietal, temporal lobes and occipital cortex) by using two markers: parvalbumin (PV) and glial fibrillary acidic protein (GFAP). Three-month old male Wistar rats were divided into control (C) and alcohol-exposed groups. The control group received distilled water, whereas the alcohol-exposed groups received either a low dose (2g/kg body wt) or a high dose (5g/kg) of ethanol for periods of 21 days, 3 or 6 months. The brains of the animals were processed for immunohistochemistry using anti-parvalbumin and anti-GFAP antibodies and the number of PV immunoreactive (PV-ir) neurons and GFAP immunoreactive (GFAP-ir) astrocytes were counted per unit area. Results showed that all groups exposed to ethanol had significantly reduced numbers of PV-ir neurons in all parts of the cerebral cortex compared to those of the control group (p

Chronic excessive alcohol administration has been reported to be associated with diastolic dysfunction. Parvalbumin (PV) is a calcium-binding protein present in cardiac myocytes and involved in mediating relaxation. Therefore, alteration of PV levels may affect relaxation in cardiac myocytes. This study investigated the effects of alcohol administration on the levels of PV in the rat heart. Male Wistar rats weighing 200-250 g were divided into 2 groups: control (C) and alcohol-treated groups. The control group was provided with distilled water and the alcohol groups were provided with either a low dose (LD, 2g/kg) or high dose of ethanol (HD, 5 g/kg) once daily for 21 days, 3 months or 6 months. The PV levels in the ventricles were investigated by immunohistochemistry and Western blot analysis. In the 21-day ethanol-treated groups, parvalbumin immunoreactivity (PV-ir) and protein levels were not different when compared to the C, LD and HD groups. In the 3-month ethanol-treated groups, PV-ir and PV protein levels were decreased in both the LD and HD groups compared to that of the control group. In the 6-month ethanol-treated groups, PV-ir and PV protein levels decreased significantly in both the LD and HD groups (P0.05). This indicates that short-term ethanol treatment may not affect PV levels, whereas, long-term ethanol treatment clearly reduced PV levels. The decrease of PV was predominantly due to the direct toxic effects of alcohol rather than malabsorption caused by pathological changes in the duodenum and liver. The toxic effects of alcohol leading to a reduction of PV levels may lead to diastolic impairment.

Parvalbumin (PV), which is a small (12kDa) cytoplasmic calcium-binding protein, has been implicated in mediating relaxation in cardiac myocytes. The influence of aging and exercise on the distribution of PV in rat heart was investigated. Male Wistar rats aged 3, 6, 12 and 18-months were divided into sedentary and exercise groups. The exercise group underwent exercise in the form of regular swimming for 6 months. The hearts were processed for immunohistochemistry and Western blotting. The intensity of PV immunoreactivity was strong in the 9 and 12-month hearts and decreased in the 18-month hearts. The smallest amount was detected in the 24-month rat hearts when compared to those of the 9, 12 and 18-month rat hearts. Significantly less PV was detected in the 18 and 24-month hearts compared to the 12-month rat hearts (P

Mitragyna speciosa (MS) has been traditionally used for medicinal purposes especially in southern Thailand. Previously, an alkaloid extract of this plant was demonstrated to mediate antinociception, partly, through the descending serotonergic system. The present study investigated the stimulatory effect of the MS extract on the dorsal raphe nucleus and its antidepressant-like activity. The MS extract containing approximately 60% mitragynine as a major indole alkaloid was used to treat the animals. The stimulatory effect of the MS extract was determined by detecting the expression of the immediate early gene, cfos, in the dorsal raphe nucleus of male Wistar rats. The immunohistochemistry was used to detect Fos protein, the protein product of cfos gene. The present data show that a significant increase in Fos expression was observed following long-term administration of the MS extract (40 mg/kg) for 60 consecutive days. In addition, the antidepressant-like activity of the MS extract was determined by using the forced swimming test (FST) in male mice. The results show that a single injection (either 60 or 90 mg/kg doses) significantly decreased immobility time in the FST. These findings indicate that the MS extract has a stimulatory effect on the dorsal raphe nucleus and an antidepressant-like activity. Stimulation of this brain area has been known to cause antinociception. These findings suggest that the MS extract might produce antinociceptive and/or antidepressive actions partly through activation of the dorsal raphe nucleus. Moreover, the dorsal raphe nucleus may be one of site of MS action in the central nervous system.

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.

In the present study, we investigated the effect of the dichloromethane fraction from Areca catechu nut on the severity of naloxone-precipitated morphine withdrawal in morphine-dependent mice. A single intraperitoneal injection of dichloromethane fraction at dose of 125 and 175 mg/kg significantly delayed the onset of withdrawal jumping behavior in a concentration-dependent manner compared to that of saline controls. The dichloromethane fractions also significantly decreased jumping numbers and faecal and urinary excretions during the withdrawal period.

Systemic or central administration of growth-hormone secretagogues (GHS) induces dense Fos expression in the arcuate nucleus but little or no Fos expression in the ventromedial hypothalamic nucleus, although both sites show intense expression of mRNA for the GHS receptor. Here, we recorded the electrical activity of single neurons from the arcuate nucleus and from the ventromedial hypothalamic nucleus in a rat hypothalamic slice preparation, and compared responses of these two populations to GHS. At both sites, the predominant neuronal response to GHS was a long-lasting excitation, indicating that GHS receptors at both sites are functional and similarly coupled to electrical excitation. We also tested neurons at both sites for their responses to neuropeptide Y and to somatostatin; at both sites the predominant response to each of these peptides was inhibitory. The arcuate cells that are activated by GHS include neuropeptide Y cells and growth hormone-releasing hormone cells. It seems possible that neuropeptide Y released in the ventromedial hypothalamus from the terminals of arcuate neurons counteracts the activation of ventromedial hypothalamic neurons by GHS in vivo, or that somatostatin released following liberation of growth hormone may do so.

The pharmacological properties of the ephedrine derivative pseudoephedrine were investigated at the nuclear level. Following intraperitoneal injection of Sprague‐Dawley rats with pseudoephedrine, Fos induction was measured in various brain areas by Western blots and immunocytochemistry. Pseudoephedrine induced Fos-like immunoreactivity in the nucleus accumbens and striatum in a time and concentration-dependent manner with maximal effect at 60 mg:kg 2 h after injection. Immunocytochemical studies confirmed that the majority of the signal was detectable in the nucleus accumbens and striatum. Pre-injection with the D1 dopamine receptor antagonist SCH23390 partially and completely blocked pseudoephedrine-induced Fos-like immunoreactivity in the striatum and nucleus accumbens, respectively, suggesting that the action of pseudoephedrine is mediated via dopamine release and results in the activation of D1 dopamine receptors. With the exception of the higher doses required, the actions of pseudoephedrine were similar to those previously described for the psychostimulant amphetamine. © 1999 Elsevier Science Ltd. All rights reserved.