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Diphenylarsinic acid (DPAA), an artificial phenyl arsenic compound, is considered a groundwater pollutant in Japan. Previous human and animal studies suggested that DPAA affects the central nervous system; however, these effects are poorly understood. The present study investigated the toxicokinetic characteristics and effects of DPAA on dopamine (DA) in the striatum of free-moving mice after a single oral administration. In a simultaneous blood and brain microdialysis study, only DPAA was detectable in both blood and striatum dialysate samples immediately after DPAA administration. DPAA concentrations in the striatum and blood dialysate rapidly reached a maximum, then decreased over time in an essentially parallel manner. A more detailed brain microdialysis examination of intracerebral kinetics revealed that the concentration of DPAA in the striatum dialysate began to increase within 15 min, reaching a maximum approximately 1 h after administration, and then decreased with a biological half-life of approximately 2 h. Moreover, a single oral administration of DPAA at 0.5-32 mg/kg affected the extracellular DA level in the striatum. The effect on DA level changed slowly after DPAA administration, with a bell-shaped dose-response relationship. The present study suggests that DPAA is rapidly absorbed into the blood circulating in the gastrointestinal tract and passes through the blood-brain barrier to subsequently affect DA levels in the striatum in mice after a single oral administration.

Graphical abstract, Highlights • Pregnant mice were exposed to PTU to induce perinatal hypothyroidism (HypoTH) in pups. • Male offspring with HypoTH showed hyperactive behavioral phenotypes. • Dopamine (DA) turnover decreased in the striatum of male offspring with HypoTH. • Degree of DA turnover in the striatum correlated with degree of locomotion. • Male offspring with HypoTH showed augmented locomotor response to bupropion., Thyroid hormone (TH) is essential for normal brain development. TH insufficiency during early stages of development may increase the risk for attention deficit/hyperactivity disorder, in which malfunction of brain monoaminergic systems is likely involved. However, little is known about the effects of perinatal hypothyroidism on behaviors and brain monoaminergic systems in offspring mice. The present study examined in mice (1) whether perinatal hypothyroidism causes hyperactive behavioral phenotypes, (2) how perinatal hypothyroidism influences brain monoaminergic systems, and (3) whether hyperactive behavioral phenotypes are associated with the state of brain monoaminergic systems. When dams were exposed to propylthiouracil, offspring mice developed hypothyroidism during the perinatal period. Offspring mice with perinatal hypothyroidism exhibited hyperactive behavioral phenotypes such as hyper-ambulatory activity and an increased response rate in the two-way active avoidance test in a male-specific manner. Significant decreases in dopamine (DA) and serotonin turnover were observed in the striatum (ST), nucleus accumbens, hypothalamus, and hippocampus in male mice with perinatal hypothyroidism. A significant correlation between ambulatory activity and DA turnover in the ST and an augmented ambulatory response to the DA reuptake inhibitor bupropion suggested that DA in the ST was involved in the hyper-ambulatory activity in mice with perinatal hypothyroidism.

Similar to psychostimulants, the peripheral administration of menthol promotes mouse motor activity, and the neurotransmitter dopamine has been suggested to be involved in this effect. The present study aimed to elucidate the effects of l-menthol on parts of the central nervous system that are involved in motor effects. The subcutaneous administration of l-menthol significantly increased the number of c-Fos-like immunoreactive nuclei in the dorsal striatum of the mice, and motor activity was promoted. It also increased the extracellular dopamine level in the dorsal striatum of the mice. These observations indicated that after subcutaneous administration, l-menthol enhances dopamine-mediated neurotransmission, and activates neuronal activity in the dorsal striatum, thereby promoting motor activity in mice.

Roman chamomile (Chamaemelum nobile or Anthemis nobilis) has traditionally been used for health care, health maintenance and medicinal purposes, and the essential oil obtained from the flowers is used as a basic ingredient for aromatherapy. Roman chamomile essential oil (CHA) produces psychostimulant-like effects, such as the ambulation-promoting effect, on mouse behaviour. However, mechanisms underlying the effects of CHA remain unclear. The present study aimed to identify the constituents responsible for the ambulation-promoting effect of CHA and to elucidate a possible neuronal mechanism. GC/MS analysis revealed that isobutyl angelate, isoamyl angelate and 2-methylbutyl isobutyrate were the major constituents of CHA. These compounds significantly promoted mouse ambulation, and were thus identified as the major active constituents for the ambulatory effect of CHA. The ambulatory effects were attenuated by chlorpromazine and haloperidol, suggesting that the neurotransmitter dopamine is involved in the ambulation-promoting effects of these constituents similar to already-known psychostimulants. The results suggest that CHA can change a mental condition, at least in part, through the CNS effects of the constituents identified in the current study. The results also suggest that mental effects of CHA are largely different from those of other Roman chamomile preparations due to the composition difference.

Physical growth and brain development need sufficient thyroid hormone (TH). This dataset describes serum T4 level, body weight gain and day of eye opening in offspring mice exposed to the TH synthesis inhibitor propylthiouracil (PTU) from gestational day (GD) 15 to postnatal day (PND) 25. This dataset also describes content of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT), 5-HT, and 5-hydroxyindoleacetic acid (5-HIAA) and their turnover in the hypothalamus, hippocampus, and nucleus accumbens of male offspring mice perinatally exposed to PTU. These data are referred by a research article entitled “Hyperactive behavioral phenotypes and an altered brain monoaminergic state in male offspring mice with perinatal hypothyroidism” [1].

Bupropion (BUP), a substituted phenyl-ethylamine, has been utilized for the treatment of depression and for smoking cessation, however, one concern is that BUP may increase a risk of psychosis similar to other substituted phenyl-ethylamine amphetamine (AMPH) and methamphetamine (MetAMPH). BUP promotes ambulation in mice and causes behavioral sensitization on the ambulation-promoting effect when repeatedly administered as well as AMPH and MetAMPH. The present study aimed to elucidate brain regions and monoaminergic neurotransmitters that are involved in the ambulation-promoting effect of BUP. c-Fos-like immunoreactivity (c-Fos-IR) mapping in brain in combination with measuring ambulatory activity was conducted to determine brain region(s) that is involved in the ambulatory effect of BUP. Three kinds of statistical analyses for c-Fos-IR in 24 brain regions consistently showed that c-Fos-IR in the Caudate putamen (CPu) is positively correlated with the ambulatory response to BUP. In addition, multiple regression analysis indicated that the ambulatory response is a function of c-Fos-IR not only in the CPu but also in the lateral septum nucleus (LS), median raphe nucleus (MnR), lateral globus pallidus (LGP), medial globus pallidus (MGP), locus coeruleus (LC) and ventral hypothalamic nucleus (VMH). Effects of BUP on monoaminergic neurotransmitters in the CPu were examined using in vivo microdialysis method, as the pharmacological experiments indicated that monoaminergic neurotransmitters, dopamine (DA) in particular, mediate the ambulatory response to BUP. Response of DA in the CPu to BUP was parallel to the ambulatory response, showing that DA in the CPu is involved in the ambulatory response to BUP. The present study also suggests that other brain regions such as the LC, the origin nucleus of norepinephrine (NE) neurons, and another neurotransmitter NE may also play some roles for the ambulatory response to BUP, however, further studies are needed to elucidate the roles. Keywords: Mouse, Ambulatory activity, Striatum, Dopamine, c-Fos mapping, Microdialysis

The present study aimed to clarify whether dose–response profiles of acute behavioral effects of 1,2-dichloroethane (DCE), 1,1,1-trichloroethane (TCE), trichloroethylene (TRIC), and tetrachloroethylene (PERC) differ. A test battery involving 6 behavioral endpoints was applied to evaluate the effects of DCE, TCE, TRIC, and PERC in male ICR strain mice under the same experimental conditions. The behavioral effect dose–response profiles of these compounds differed. Regression analysis was used to evaluate the relationship between the dose–response profiles and structural and physical properties of the compounds. Dose–response profile differences correlated significantly with differences in specific structural and physical properties. These results suggest that differences in specific structural and physical properties of DCE, TCE, TRIC, and PERC are responsible for differences in behavioral effects that lead to a variety of dose–response profiles.

Although plant-derived essential oils (EOs) have traditionally been used for treating various kinds of mental disorders, their Central Nervous System (CNS) acting effects have not yet been clarified well. The present study examined effects of 30 kinds of EOs on ambulatory activity, a kind of spontaneous motor activity, in ICR mice. Nineteen kinds of them did not produce any significant effects on the ambulatory activity of mice. Although effects of EOs of lavender, jasmine and neroli on the activity were statistically significant, their CNS acting properties remained unclear. EOs of peppermint, chamomile, thyme, tea tree, rosemary and basil significantly increased the ambulatory activity of mice as well as CNS stimulants, suggesting that they possess CNS stimulant-like effects. In contrast, an EO of myrtle significantly decreased the activity as well as CNS depressants, suggesting that it possesses a CNS depressant-like effect. An EO of palmarosa significantly increased the activity at a lower dose and decreased at a higher dose as well as some kinds of CNS depressants such as ethanol, suggesting that it also possesses a CNS depressant-like effect. These 8 kinds of EOs might be useful for treating some kinds of mental troubles and/or symptoms through their CNS acting effects.

The present study examined the effect of nicotine, alone and in combination with various drugs that act on the CNS, on ambulatory activity, a behavioral index for locomotion, in ICR (CD-1) strain mice. Nicotine at 0.25–2 mg/kg acutely reduced ambulatory activity of ICR mice. The effect of nicotine was similar to that of haloperidol and fluphenazine but distinct from that of bupropion and methylphenidate. ICR mice developed tolerance against the inhibitory effect of nicotine on ambulatory activity when nicotine was repeatedly administered. This effect was also distinct from bupropion and methylphenidate as they produced augmentation of their ambulation-stimulating effects in ICR mice. Nicotine reduced the ambulation-stimulating effects of bupropion and methylphenidate as well as haloperidol and fluphenazine. Taken together, nicotine exhibited unusual effects as a psychostimulant on ambulatory activity in ICR mice.

Citizens in an area of Kamisu City, Ibaraki, Japan had exhibited unusual health problems, and pollution of well water by diphenylarsinic acid (DPAA) was found in the area. We examined the effects of DPAA on various behaviors in mice. DPAA was administered to mice through free intake of drinking water for 27 weeks (subchronic exposure) or 57 weeks (chronic exposure), and behavior was examined during exposure. DPAA at 30-100 ppm increased ambulatory activity and the response rate of the shuttle type discrete conditioned avoidance response of mice. DPAA reduced coordination ability on the fixed rod at 100 ppm. DPAA at 7.5-15 ppm also reduced coordination on the rotating rod, although these doses of DPAA did not affect coordination on the fixed rod. Chronic exposure to 7.5-15 ppm of DPAA produced anti-anxiety-like effects in the elevated plus maze test, whereas subchronic exposure to 100 ppm of DPAA produced anxiogenic-like effects. Neither subchronic nor chronic exposure to 7.5-100 ppm of DPAA affected learning ability and/or memory, as evaluated using the passive avoidance response. Exposure to 15-30 ppm of DPAA for 52 weeks did not alter weights of the cerebrum and cerebellum or amounts of neuron marker protein TUJ-1 or astrocyte marker protein glial fibrillary acidic protein in the cerebellum of mice. Behavioral effects observed in mice seem relevant to symptoms observed in patients from Kamisu City.

Although plant-derived essential oils (EOs) have been used to treat various mental disorders, their central nervous system (CNS) acting effects have not been clarified. The present study compared the effects of 20 kinds of EOs with the effects of already-known CNS acting drugs to examine whether the EOs exhibited CNS stimulant-like effects, CNS depressant-like effects, or neither. All agents were tested using a discrete shuttle-type conditioned avoidance task in mice. Essential oils of peppermint and chamomile exhibited CNS stimulant-like effects; that is, they increased the response rate (number of shuttlings/min) of the avoidance response. Linden also increased the response rate, however, the effect was not dose-dependent. In contrast, EOs of orange, grapefruit, and cypress exhibited CNS depressant-like effects; that is, they decreased the response rate of the avoidance response. Essential oils of eucalyptus and rose decreased the avoidance rate (number of avoidance responses/number of avoidance trials) without affecting the response rate, indicating that they may exhibit some CNS acting effects. Essential oils of 12 other plants, including juniper, patchouli, geranium, jasmine, clary sage, neroli, lavender, lemon, ylang-ylang, niaouli, vetivert and frankincense had no effect on the avoidance response in mice.

It has been proposed that essential oil extracted from Abies sachalinensis (EOAS) has a relaxation effect, among others, in humans; however, the scientific evidence is currently insufficient. To clarify the influence of EOAS on emotional behaviour, we examined its anxiolytic-like effect using a mouse model. The elevated plus maze task was used to evaluate the anxiolytic-like effect. The results showed that intraperitoneal (i.p.) administration of EOAS at 0.6 g/kg body weight did not produce an anxiolytic-like effect. However, a significant anxiolytic-like effect was observed after inhalation of EOAS at 3.6 mg/l air (P

I investigated whether dopamine (DA) is involved in the ambulation promoted by pulegone (PUL), a constituent of peppermint oil, in ICR mouse. Co-administration of PUL and bupropion (BUP) had an additive effect on their ambulation-promoting activities. When administered with PUL, the DA antagonists chlorpromazine, fluphenazine, haloperidol, SCH12679, and spiperone all attenuated the effect of PUL on ambulation. In addition, pretreatment with the DA depletor reserpine produced no subsequent sensitivity to the effect of PUL. Taken together, DA may be involved in the ability of PUL to promote ambulation in ICR mice but PUL may not be a direct DA agonist. The chemical structure of PUL is similar to menthol and menthone, and thus they may all be acting through a common mechanism.

Ultraviolet (UV) sunscreen products are popular because of concerns about UV radiation and skin cancer. Unfortunately, some of these products contain agents with estrogenic activity. We used an ovariectomized rat uterotrophic assay to measure the estrogenic activities of 2,4-dihydroxybenzophenone (2,4-DHBP), 2,2',4,4'-tetrahydroxybenzophenone (2,2',4,4'-THBP), and 4-hydroxybenzoic acid isobutyl ester (isobutyl-paraben), which are agents in UV sunscreens, and ethynyl estradiol (EE) and bisphenol A (BPA), which are positive controls. All chemicals increased rat uterine weights. The 10% effective doses (ED10, mg/kg/day) of EE, BPA, 2,4-DHBP, 2,2',4,4'-THBP, and isobutyl-paraben, as determined by Hill equation analysis, where 5E-5, 41.1, 544.6, 33.0, and 230.9, respectively, and their relative potencies against EE were about 1/800,000, 1/10,000,000, 1/600,000, and 1/4,000,000, respectively. Our findings indicated that UV screens contain weak estrogenic compounds.

The present study examines the mechanism that underlies the ability of menthol (ME), a major constituent of peppermint oil, to promote mouse ambulation. We initially confirmed that bupropion (BUP), a dopamine (DA) uptake inhibitor, promotes ambulation in ICR mice. Since the subcutaneous administration of ME produced similar effects in mice, we investigated the effects of ME on ambulation when combined with BUP. The results showed that BUP potentiated the effect of ME on mouse ambulation. We then examined effects of the DA antagonists chlorpromazine, haloperidol, fluphenazine, spiperone, and SCH12679 on the ability of BUP and ME to promote ambulation. All of these DA antagonists attenuated the effects of BUP and ME. Prior exposure to reserpine, which depletes monoamines, caused decreased sensitivity to the ability of BUP and of ME in promoting ambulation. The tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine, similarly decreased subsequent sensitivity to the effects of BUP and ME. These results suggest that DA is involved in the abilities of ME and BUP to promote ambulation in mice.

The present study investigates the pharmacologically active constituents of rose oil, which possesses anti-conflict effects. Analysis using GC/MS revealed that rose oil contains 9 substances that were identified as myrcene, benzyl alcohol, 2-phenethyl alcohol, citronellol, geraniol, citronellyl acetate, eugenol, geranyl acetate and methyl eugenol. We examined the effects of each of these substances using the Geller and Vogel conflict tests in ICR mice. Myrcene, benzyl alcohol and citronellyl acetate did not produce any effects in either tests. Geranyl acetate and methyl eugenol produced no effect in the Geller conflict test. Geraniol and eugenol decreased the response rate during the safe period of the Geller conflict test, but did not affect the response rate during the alarm period. In contrast, 2-phenethyl alcohol and citronellol, like rose oil, produced an increasing effect on the response rate during the alarm period in the Geller conflict test. In addition, both chemicals increased the number of electric shocks mice received in the Vogel conflict test in a manner similar to that of rose oil. Given that 2-phenethyl alcohol and citronellol produced the same anti-conflict effects in both tests as rose oil, we concluded that they are the pharmacologically active constituents of anti-anxiety-like effect of rose oil.

The present study was conducted to clarify the acute effect of tris(2-chloroethyl)phosphate (TRCP), an organophosphate flame-retardant, on spontaneous ambulatory activity (AA) in male ICR mice and to examine the neurochemical mechanism of this effect. Single dose administration of 200 mg/kg ip of TRCP increased AA in ICR mice. Neither the nicotinic cholinergic antagonist mecamylamine (MA) nor the muscarinic cholinergic antagonist scopolamine (SCP) affected the AA response to TRCP. On the other hand, the benzodiazepine agonist diazepam (DZ), the GABAAagonist muscimol (MUS) and the GABABagonistbaclofen (BAC) all attenuated the effect of TRCP. DZ and MUS blocked the increase of AA within the first 10 min after administration of TRCP. These drugs did not attenuate the AA-increasing effect of SCP, suggesting that the mechanism of TRCP action is distinct from that of SCP. MUS and BAC did, but DZ did not, inhibit the AA increasing effect of the dopaminergic agonist apomorphine (APO), suggesting that dopamine is involved in the control of AA, and that GABA can affect AA through interaction with dopaminergic neurons. These results suggest that TRCP acts as a GABA antagonist and not as a cholinergic agonist, and that TRCP increases AA in ICR mice through a GABAergic mechanism.

This study exammed the effects of intermittent exposures to 0.4–0.8 ppm ozone (O3) on drinking and eating behaviors in rats to evaluate the development of tolerance to O3 exposure. When rats were exposed to 0.4 ppm (787 μg/m3) O3 for 23 h the first time, the drinking activity was reduced to 29% of the control value and the eating activity to 44%. A decrease in body weight (mean decrease 11 g) was also noted. However, the magnitude of these changes was attenuated when the rats were exposed to 0.4 ppm O3 on day 2, 4, or 7 after the first exposure. When rats were exposed to 0.4 ppm O3 and then to 0.8 ppm (1577 μg/m3) O3 7 days later, the magnitude of decrease in the drinking activity was considerably smaller during the second exposure compared with that of a single exposure to 0.8 ppm O3. The lowered drinking activity by O3 exposure did not produce a postexposure compensatory increase of water intake. Moreover, deprivation of food and water prior to O3 exposure scarcely affected decrease in drinking ...

Male ICR mice were exposed continuously to ozone (O 3 ) and nitrogen dioxide (NO 2 ) for 7 days to examine the effects on drinking and eating behaviors. Ozone at 0.1 ppm did not affect drinking and eating activities, whereas drinking activity decreased in a concentration-dependent manner to 47.7, 12.8. and 3.0% of the control value with 2-day exposures to 0.2, 0.4, and 0.8 ppm O 3 , respectively, and eating activity decreased to 35.2 and 8.7% of the control value at 0.4 and 0.8 ppm O 3 , respectively. Body weight also decreased markedly by 2.0, 4.6, and 7.5 g at 0.2, 0.4, and 0.8 ppm O 3 , respectively. These decrements reached a maximum on the second day of exposure. However, alterations in drinking and eating activities and body weight were transient, leading to recovery during the continuous O 3 exposures. The recovery processes were dependent on the concentrations of O 3 . Nitrogen dioxide at 4 ppm did not affect drinking and eating activities, whereas drinking activity decreased in a concentration-dependent manner to 56.8, 8.3, and 18.7% of the control value with 2-day exposures to 6, 8, and 12 ppm NO 2 , respectively, and eating activity decreased markedly to 21.8 and 16.4% at 8 and 12 ppm NO 2 , respectively. Body weight also decreased by 2.5, 5.5, and 6.1 g at 6, 8, and 12 ppm NO 2 , respectively. These decrements reached a maximum on the second day of exposure. As in the O 3 exposures, the decrements in drinking and eating activities and body weight were transient and recovered during the continuous exposures to NO 2 depending on the concentrations of NO 2 . Drinking and eating activities and body weights of mice that had been previously exposed to 12 ppm NO 2 for 7 days did not show changes when the mice were exposed to 0.4 ppm O 3 9 days after NO 2 exposure. The present study demonstrates that photochemical oxidants suppress drinking and eating behaviors in mice and that they recover thereafter under the continuous exposure conditions.

The present study examines the mechanism that underlies the ability of menthone (MTN), a constituent of peppermint oil, to promote mouse ambulation. Since bupropion (BUP), a dopamine (DA) uptake inhibitor, promotes mouse ambulation, the effect of MTN combined with BUP on ambulation was investigated. The results showed that BUP with MTN produced an additive interaction on mouse ambulation. The effects of DA antagonists chlorpromazine, fluphenazine, haloperidol, SCH12679 and spiperone on the ability of MTN to promote ambulation were then examined. All of these antagonists attenuated the effects of MTN. Prior exposure to the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine, which inhibits catecholamines synthesis, decreased subsequent sensitivity to the effect of MTN. These results suggest that DA is involved in the ability of MTN to promote ambulation in mice.

The pharmacological effects of lavender oil were investigated using two conflict tests in ICR mice, and then the active constituents were identified. Lavender oil produced significant anticonflict effects at 800 and 1600 mg/kg in the Geller conflict test and at 800 mg/kg in the Vogel conflict test, suggesting that the oil has an anti-anxiety effect. Analysis using GC/MS revealed that lavender oil contains 26 constituents, among which alpha-pinene (ratio, 0.22%), camphene (0.06%), beta-myrcene (5.33%), p-cymene (0.3%), limonene (1.06%), cineol (0.51%), linalool (26.12%), borneol (1.21%), terpinene-4-ol (4.64%), linalyl acetate (26.32%), geranyl acetate (2.14%) and caryophyllene (7.55%) were identified. We examined the effects of linalool, linalyl acetate, borneol, camphene, cineol, terpinen-4-ol, alpha-pinene and beta-myrcene using the Geller and Vogel conflict tests in ICR mice. Cineol, terpinen-4-ol, alpha-pinene and beta-myrcene did not produce any significant anticonflict effects in the Geller test. Linalyl acetate did not produce any significant anticonflict effects in either test. Both borneol and camphene at 800 mg/kg produced significant anticonflict effects in the Geller, but not in the Vogel conflict test. Linalool, a major constituent of lavender oil, produced significant anticonflict effects at 600 and 400 mg/kg in the Geller and Vogel tests, respectively, findings that were similar to those of lavender oil. Thus, we concluded that linalool is the major pharmacologically active constituent involved in the anti-anxiety effect of lavender oil.

Because reproductive tracts in ovariectomized rodents, which are commonly used in endocrinological studies, exhibit drastic changes in response to exogenous estrogens, quantitative evaluation of gene expression requires extra caution. We found that the whole mRNA content of total RNA in the uterus of the ovariectomized rat was dose-dependently reduced by treatment with 17α-ethynylestradiol (EE) for 3 consecutive days. Because of the decline in the ratio of mRNA/total RNA, real-time reverse transcriptase-polymerase chain reaction analysis seemingly showed that the relative ratios of the levels of stable RNAs, rRNA18S, rRNA5S, and tRNA-Gly, to whole mRNA were increased by EE. These results indicate that applying a fixed concentration of total RNA and stable RNA as an internal control to uterine mRNA quantification should be reconsidered. On the other hand, the β-actin gene showed the most stable expression among the housekeeping genes examined. Using β-actin mRNA as an internal control, we observed that tissue inhibitor of metalloproteinase-3 (TIMP3) mRNA was dose-dependently reduced 24 h after treatment with EE or bisphenol A for 3 days. Continued investigation of TIMP3 with an appropriate internal control may be helpful in elucidating the mechanisms involved in uterine activation.

Various plant-derived essential oils (EOs) have traditionally been used in the treatment of mental disorders, despite a lack of scientific evidence. In a previous study, we demonstrated that certain EOs possess behavioral effects, a finding that supports our original hypotheses that EOs possess psychoactive actions. The present study was conducted in order to obtain further evidence to support our hypothesis. Peppermint oil, a type of EO, is believed to be effective for treating mental fatigue. When the oil was administered intraperitoneally to ICR mice, the ambulatory activity of mice increased dramatically. We identified alpha-pinene, beta-pinene, (R)-(+)-limonene, 1,8-cineol, isomenthone, menthone, menthol, (R)-(+)-pulegone, menthyl acetate and caryophyllene as constituent elements of peppermint oil by GC-MS analysis. We then examined the effect of each constituent element of peppermint oil on ambulatory activity in mice. Intraperitoneal administration of 1,8-cineol, menthone, isomenthone, menthol, (R)-(+)-pulegone, menthyl acetate and caryophyllene significantly increased ambulatory activity in mice, suggesting that these chemicals are the behaviorally active elements of peppermint oil. Intravenous administration of these substances to mice induced a significant increase in ambulatory activity at much lower doses. The present study provides further evidence demonstrating that EOs possess pharmacological actions on behavior. In addition, our finding revealed that the action of peppermint oil comes from its constituent elements.

In hamsters homozygous for the circadian clock mutation tau, the photic history dramatically affects the magnitude of light-induced circadian phase shifts. The maximum amplitude of phase shifts produced by 1-h light pulses presented at CT 14 was less than 2 h in animals that had been in DD for 2 days, whereas animals that had been kept in DD for 49 days could be shifted by more than 8 h. In this study, the authors compared the effect of previous light history on the amplitude of circadian phase shifts and on c- fos expression in the SCN of tau mutant hamsters. Although the maximum amplitude of behavioral phase shifts was drastically different between animals that had been held for either 2 or 49 days in DD, maximal fos induction was not significantly different in these two groups. However, photic thresholds for light-induced behavioral phase shifts, c- fos mRNA, and Fos immunoreactivity were closely correlated within both groups, and these thresholds were lower (more sensitive to light) after 49 than after 2 days in DD. The correlation between phase shifting and Fos induction thresholds, under conditions where both responses are dramatically altered by the previous light history, demonstrates an association between changes in circadian behavioral phase-shifting responses of tau mutant hamsters and plasticity of light-induced c- fos expression in SCN. However, because the maximum amplitudes of Fos induction and phase shifting were not correlated in animals that had been in DD for 2 days, we speculate that the level of c- fosexpression does not directly determine phase shift amplitude.

This study was performed to clarify the toxicological profiles of trichloroethylene (TRCE) and tetrachloroethylene (TECE) when they are administered intraperitoneally in mice. The ED50 for loss of righting reflex were 2596 mg/kg in TRCE and 4209 mg/kg in TECE. TRCE and TECE impaired bridge test performance at 500 and 2000 mg/kg, respectively. An operant behavior performance was also inhibited by TRCE at 1000 mg/kg and by TECE at 2000 mg/kg. Both TRCE and TECE exhibited anticonflict effects in a Vogel-type task at 500 mg/kg. This effect was confirmed by the finding that TRCE exhibited anticonflict action in a Geller-type paradigm at 250 mg/kg and more, as did TRCE did at 1000 mg/kg. These results show that TRCE and TECE affect various behaviors in mice and suggest that conflict behaviors are one of the most sensitive behavioral indicators of the effects of these substances. The toxicological profiles of TRCE and TECE with respect to behavioral effects were very similar, and they can be classified in a single category.

Male ICR mice were exposed continuously to ozone (O3) and nitrogen dioxide (NO2) for 7 days to examine the effects on drinking and eating behaviors. Ozone at 0.1 ppm did not affect drinking and eating activities, whereas drinking activity decreased in a concentration-dependent manner to 47.7, 12.8, and 3.0% of the control value with 2-day exposures to 0.2, 0.4, and 0.8 ppm O3, respectively, and eating activity decreased to 35.2 and 8.7% of the control value at 0.4 and 0.8 ppm O3, respectively. Body weight also decreased markedly by 2.0, 4.6, and 7.5g at 0.2,0.4, and 0.8 ppm O3, respectively. These decrements reached a maximum on the second day of exposure. However, alterations in drinking and eating activities and body weight were transient, leading to recovery during the continuous O3 exposures. The recovery processes were dependent on the concentrations of O3. Nitrogen dioxide at 4 ppm did not affect drinking and eating activities, whereas drinking activity decreased in a concentration-dependent manner to 56.8, 8.3, and 18.7% of the control value with 2-day exposures to 6, 8, and 12 ppm NO2, respectively, and eating activity decreased markedly to 21.8 and 16.4% at 8 and 12 ppm NO2, respectively. Body weight also decreased by 2.5, 5.5, and 6.1 g at 6, 8, and 12 ppm NO2, respectively. These decrements reached a maximum on the second day of exposure. As in the O3 exposures, the decrements in drinking and eating activities and body weight were transient and recovered during the continuous exposures to NO2 depending on the concentrations of NO2. Drinking and eating activities and body weights of mice that had been previously exposed to 12 ppm NO2 for 7 days did not show changes when the mice were exposed to 0.4 ppm O3 9 days after NO2 exposure. The present study demonstrates that photochemical oxidants suppress drinking and eating behaviors in mice and that they recover thereafter under the continuous exposure conditions. © 1993 Academic Press, Inc.

To clarify the effects of ozone on behavior, drinking activity was observed continuously in animals exposed to ozone at concentrations of 0.2, 0.4, and 0.8 ppm for 1 wk. Drinking decreased considerably on the first day after onset of exposure. On the first day the suppression rate was calculated to be 28.1%, 69.5%, and 93.1%, for the 0.2 ppm, 0.4 ppm, and 0.8 ppm group, respectively. The suppression of drinking and recovery were dependent on the concentration of ozone.

The Vogel-type conflict task, in which drinking of water by animals is punished by electric shock, is well known as a simple conflict procedure, and has come into wide use. This task has almost been established in rats. On the other hand, there are only few reports about application of the task to mice, and such studies have not proceeded smoothly. This report presents technical problems in the application of the task to mice based on various experiments, in which experimental conditions such as procedures, intensity of electric shock and mouse strain differed, in order to determine the anti-conflict action of diazepam (DZ). These experiments showed that successful detection of DZ action depended upon the experimental conditions. Therefore, experimental designs are important in evaluating anti-conflict action of chemicals in the Vogel-type task in mice.