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It is the first and important practice for the study of the psychotropic drugs to observe the spontaneous movement of animals. Although many methods have been known for measuring the spontaneous movements, most of them are to find the change of motor activity of a single animal. Many investigators reported the automatic measurement of the motor activity. Photoelectric method was first used by Siegel et al. (1), which was improved by Dews et al. (2) in mice. Takagi et al. (3) traced the spontaneous movement of a mouse using a modified photoelectric apparatus. The central nervous system stimulant effect of 2-dimethylaminoethanol (DMAE) was first reported by Pfeiffer et al. (4) and had been confirmed by Konigsmark et al. (5), Himwich (6) and Brown and Gangloff (7). It was also confirmed by clinical trials. Pfeiffer et al. (8) proposed the hypothesis that DMAE played the role of a precursor of acetylcholine in the central nervous system. Groth et al. (9) found that DMAE was incorporated in the mouse brain more rapidly than choline and probably converted to brain choline. However, Pepeu et al. (10) and Kiplinger et al. (11) had different views from that of Pfeiffer. In this paper, we have developed a method of recording the spontaneous activity of grouped mice, in order to take an accurate measurement of a little change of motor activity by drugs. We investigated the effect of DMAE and its acyl esters on the spontaneous movement of the grouped and/or individual mice.

Cerebellar alterations are a hallmark of Fetal Alcohol Spectrum Disorders and are thought to be responsible for deficits in fine motor control, motor learning, balance, and higher cognitive functions. These deficits are, in part, a consequence of dysfunction of cerebellar circuits. Although the effect of developmental ethanol exposure on Purkinje and granule cells has been previously characterized, its actions on other cerebellar neuronal populations are not fully understood. Here, we assessed the impact of repeated ethanol exposure on the number of inhibitory neurons in the cerebellar vermis. We exposed pregnant mice to ethanol in vapor inhalation chambers during gestational days 12-19 and offspring during postnatal days 2-9. We used transgenic mice expressing the fluorescent protein, Venus, in GABAergic/glycinergic neurons. Using unbiased stereology techniques, we detected a reduction in Venus positive neurons in the molecular and granule cell layers of lobule II in the ethanol exposed group at postnatal day 16. In contrast, ethanol produced a more widespread reduction in Purkinje cell numbers that involved lobules II, IV-V and IX. We also found a reduction in the volume of lobules II, IV-V, VI-VII, IX and X in ethanol-exposed pups. These findings indicate that second and third trimester-equivalent ethanol exposure has a greater impact on Purkinje cells than interneurons in the developing cerebellar vermis. The decrease in the volume of most lobules could be a consequence of a reduction in cell numbers, dendritic arborizations, or axonal projections.

ABSTRACT We tested whether Sake Lees (SL) had inhibitory effects on hyperalgesia in the hindpaw under psychophysical stress conditions. Male rats were subjected to repeated forced swim stress treatments (FST) from Day −3 to Day −1. Intraperiotoneal administration of SL which contained low concentration of ethanol (SLX) was conducted after each FST. On Day 0, formalin-evoked licking behaviors and Fos responses in the lumbar spinal cord (DH) and several areas within the rostral ventromedial medulla (RVM) were quantified as nociceptive responses. FST-induced hyperalgesia in the hindpaw was prevented by repeated SL and SLX treatments. Fos expression was significantly increased in DH and some areas within the RVM under FST, which was prevented by repeated SL or SLX. These findings indicated that daily administration of SL had the potential to alleviate stress-induced hyperalgesia.

Sigma-1 receptor (Sig-1R) has been proposed as a novel therapeutic target for drug and alcohol addiction. We have shown previously that Sig-1R agonists facilitate the reinforcing effects of ethanol and induce binge-like drinking, while Sig-1R antagonists on the other hand block excessive drinking in genetic and environmental models of alcoholism, without affecting intake in outbred non-dependent rats. Even though significant progress has been made in understanding the function of Sig-1R in alcohol reinforcement, its role in the early and late stage of alcohol addiction remains unclear. Administration of the selective Sig-1R antagonist BD-1063 dramatically reduced the acquisition of alcohol drinking behavior as well as the preference for alcohol in genetically selected TSRI Sardinian alcohol preferring (Scr:sP) rats; the treatment had instead no effect on total fluid intake, food intake or body weight gain, proving selectivity of action. Furthermore, BD-1063 dose-dependently decreased alcohol-seeking behavior in rats trained under a second-order schedule of reinforcement, in which responding is maintained by contingent presentation of a conditioned reinforcer. Finally, an innate elevation in Sig-1R protein levels was found in the nucleus accumbens of alcohol-preferring Scr:sP rats, compared to outbred Wistar rats, alteration which was normalized by chronic, voluntary alcohol drinking. Taken together these findings demonstrate that Sig-1R blockade reduces the propensity to both acquire alcohol drinking and to seek alcohol, and point to the nucleus accumbens as a potential key region for the effects observed. Our data suggest that Sig-1R antagonists may have therapeutic potential in multiple stages of alcohol addiction.

AbstractThis study involved mice that received 4 days of ethanol (EtOH) vapor inhalation and then were assessed for type 1 inositol 1,4,5‐trisphosphate receptor (IP3Rs‐1) expression and the development of EtOH‐induced place preference at various time points in withdrawal. IP3R‐1 protein was found to be significantly increased in the nucleus accumbens (NAcc) of mice immediately after 4‐day EtOH vapor inhalation, while it significantly reduced to the control level during the next 3 days of withdrawal from EtOH inhalation. EtOH (2 g/kg, i.p.)‐induced place preference after 3 days of withdrawal from EtOH vapor inhalation increased dose dependently for 4 days, which was significantly inhibited by 2‐aminophenoxyethane‐borate, an antagonist for IP3Rs. EtOH conditioning significantly increased, compared to alcohol‐naïve control mice, both IP3R‐1 protein and the release of dopamine in the NAcc of mice after 3 days of withdrawal from EtOH vapor inhaled for 4 days, and this increase of IP3R‐1 protein was completely abolished by intracerebroventricular injection of FK506, an inhibitor for calcineurin. These results indicate that the sensitization of EtOH‐induced place preference is due to up‐regulated IP3R‐1 via calcineurin‐mediated pathway after enhanced release of dopamine in the NAcc on EtOH administration during EtOH conditioning. image We revealed signal transduction pathways that may promote sensitization of ethanol (EtOH)‐induced place preference. EtOH facilitated the release of dopamine (DA) in the Nucleus accumbens (NAcc), enhancing calcineurin function via dopamine D1‐like and D2‐like receptor activation, which in turn resulted in increased NFATc4 expression. Increase in NFATc4 may further facilitate transcription factor binding to IP3R‐1 promoter domain to stimulate IP3R‐1 synthesis. Such increased IP3R‐1 elevates intracellular Ca2+ concentration via facilitated mobilization of Ca2+ from the intracellular Ca2+ stores to the cytosol.

Sedentary/inactive lifestyle leads middle-aged and older adults to metabolic syndrome and frailty. Capsinoids from nonpungent chili pepper cultivar have been reported to reduce body fat mass, promote metabolism, and improve unidentified complaints of chills. Additionally, they have an anti-inflammation effect; therefore, we hypothesized that continuous oral ingestion of capsinoids alleviates age-related inflammation in the brain and improves the physical activity (PA) in middle-aged and older adults. In our double-blind human study, 69 participants (17 male, 52 female; mean age: 74.1 ± 7.7 years; range: 52–87 years) were administered either 9 mg of capsinoids which were extracted from pepper fruit variety CH-19 Sweet (Capsicum anuum L.) (CP group), or a placebo (PL group) daily over a 3 month period. In an animal study, PA and inflammation-related mRNA expression in the brain were examined in 5-week (young) and 53-week (old) aged mice fed a diet with or without 0.3% dihydrocapsiate, a type of capsinoids, for 12 weeks. In a human study, capsinoids intake did not increase the amount of light-to-moderate PA less than 6.0 metabolic equivalents (METs) (CP: 103.0 ± 28.2 at baseline to 108.2 ± 28.3 at 12 weeks; PL: 104.6 ± 19.8 at baseline to 115.2 ± 23.6 at 12 weeks, METs × hour/week); however, in participants exhibiting an inactive lifestyle, it showed significant increase (CP: 84.5 ± 17.2 at baseline to 99.2 ± 24.9 at 12 weeks; PL: 99.7 ± 23.3 at baseline to 103.8 ± 21.9 at 12 weeks). The energy expenditure in physical activity also improved in the inactive CP group (CP: 481.2 ± 96.3 at baseline to 562.5 ± 145.5 at 12 weeks; PL: 536.8 ± 112.2 at baseline to 598.6 ± 127.6 at 12 weeks; kcal/day). In all participants, CP showed reduced waist circumference, percent body fat, and visceral fat volume; in addition, chills were eased in subjects aged 80 years and older. The older mice fed capsinoids showed increased locomotion activity, decreased inflammation, and oxidative stress in the brain. The results suggest that the continuous oral ingestion of capsinoids gains PA through anti-inflammation effect in the brain as well as reduces fat accumulation and chills in inactive and older humans.

AbstractA patient with vasospastic angina who developed myocardial ischemia following ethanol ingestion but not after exercise was described. Myocardial ischemia was evidenced by electrocardiograms (ECGs) and thallium‐201 scintigrams. The blood acetaldehyde level after ethanol ingestion was abnormally high. The time course and severity of myocardial ischemia coincided with those of the blood ethanol and acetaldehyde level. Coronary arteriography showed ergonovine maleate‐induced coronary vasospasm at the left anterior descending coronary artery. ECG changes similar to those induced by ethanol ingestion were observed at the same time. These findings suggest that the high blood acetaldehyde level might be responsible for the development of coronary vasospasm and myocardial ischemia in this patient.