Anxiolytic effect of music depends on ovarian steroid in female mice.

Music is known to be able to elicit emotional changes, including anxiolytic effects. The gonadal steroid hormones estradiol and progesterone have also been reported to play important roles in the modulation of anxiety. In the present study, we examined whether the effect of music on anxiety is related to ovarian steroid in female mice. Behavioral paradigms measuring anxiety were tested in gonadally intact (SHAM) and ovariectomized (OVX) female mice chronically treated with either placebo (OVX/Placebo), 17beta-estradiol (OVX/E), or progesterone (OVX/P). In the elevated plus maze, light-dark transition, and marble burying tests, SHAM and OVX/P mice exposed to music showed less anxiety than those exposed to white noise or silence while OVX/placebo mice did not show these effects at all. OVX/E mice showed the anxiolytic effect of music only in the marble burying test. Furthermore, pretreatment with progesterone's metabolite inhibitor completely prevented the anxiolytic effect of music in behavioral tests, while pretreatment with a progesterone receptor blocker did not prevent the anxiolytic effect of music. These results suggest that exposure to music reduces anxiety levels, and ovarian steroids, mainly progesterone, may be involved in the anxiolytic effect of music observed in female mice.

Clock mutant mice with Jcl/ICR background shows an impaired learning ability in water maze, but not in passive avoidance, at the beginning of dark phase.

We observed the learning ability in Clock mutant mice with Jcl/ICR background (Clockj), a mice model of evening-type individuals, in the early part of dark phase. In order to estimate the learning ability, Morris water maze (WM) and passive avoidance (PA) test were performed. Release of acetylcholine, 5 hydroxytryptophan (5-HT) and dopamine (DA) in hippocampus was measured by in vivo microdialysis method. Clockj showed the impaired learning ability in the WM, but not in PA test. Hippocampal acetylcholine release was significantly attenuated in the Clockj in comparison to the wild-type mice. Neither 5-HT nor DA in the hippocampus was affected by the Clock mutation. Clock, an essential gene controlling circadian rhythm, may have an important role on the spatial learning and hippocampal cholinergic function, at least, at the beginning of the dark phase.

Exposure to music in the perinatal period enhances learning performance and alters BDNF/TrkB signaling in mice as adults.

Music has been suggested to have a beneficial effect on various types of performance in humans. However, the physiological and molecular mechanism of this effect remains unclear. We examined the effect of music exposure during the perinatal period on learning behavior in adult mice, and measured the levels of brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB), which play critical roles in synaptic plasticity. In addition, we measured the levels of 3-phosphoinositide-dependent protein kinase-1 (PDK1) and mitogen-activated protein kinase (MAPK), downstream targets of two main pathways in BDNF/TrkB signaling. Music-exposed mice completed a maze learning task with fewer errors than the white noise-exposed mice and had lower levels of BDNF and higher levels of TrkB and PDK1 in the cortex. MAPK levels were unchanged. Furthermore, TrkB and PDK1 protein levels in the cortex showed a significant negative correlation with the number of errors on the maze. These results suggest that perinatal exposure of mice to music has an influence on BDNF/TrkB signaling and its intracellular signaling pathway targets, including PDK1, and thus may induce improved learning and memory functions.

Monoamine oxidase A activity and norepinephrine level in hippocampus determine hyperwheel running in SPORTS rats.

An understanding of neurological mechanisms for wheel running by rodents, especially with high exercise activity, would be applicable to a strategy for promotion of exercise motivation in humans. One of several brain regions that are candidates for the regulation of physical exercise is the hippocampus. Here we examined the running activity of Spontaneously-Running-Tokushima-Shikoku (SPORTS) rat, a new animal model for high levels of wheel-running activity, and its relation with the hippocampal norepinephrine (NE) system including the levels of NE, adrenergic receptors, and degradation enzymes for monoamines. In the hippocampus of SPORTS rats, the level of NE in extracellular fluid was augmented, whereas the level in the homogenate of the whole tissue was decreased even for sedentary conditions. Elevated extracellular NE caused downregulation of alpha(2)-adrenergic receptors in the hippocampus of SPORTS rats. Local administration of alpha(2)-adrenergic receptor antagonist yohimbine, but not of alpha(2)-agonist clonidine, into the hippocampus suppressed high running activity in SPORTS rats. The protein expression and the activity levels of monoamine oxidase A (MAOA), a critical enzyme for the degradation of NE, were decreased in the hippocampus of SPORTS rats to increase extracellular NE level. Thus, inhibition of oxidase activity in normal Wistar rats markedly increased wheel-running activity. These results indicate that decreased MAOA activity, elevation of extracellular NE, and alpha(2)-adrenergic receptors in the hippocampus determine the neural basis of the psychological regulation of exercise behavior in SPORTS rats.

Enhanced hippocampal acetylcholine release in nociceptin-receptor knockout mice.

Nociceptin (NOC), an endogenous ligand of the opioid receptor-like 1 receptor, is thought to be involved in learning and memory processes. Since acetylcholine (ACh) is involved in hippocampal function, and the hippocampus plays a critical role on the learning and memory function, hippocampal ACh release in NOC-receptor knockout mice was examined using an in vivo microdialysis method. The release of hippocampal ACh was largely increased in the knockout mice. Furthermore, in the knockout mice, an enhanced hippocampal theta rhythm, which is known to be linked to hippocampal memory function, was also observed. Immunohistochemically, in septum, co-existence of NOC receptor with cholinergic, but not with GABAergic neurons, was verified. The findings demonstrate that the NOC receptor is involved in hippocampal cholinergic function.

Lack of nociceptin receptor alters body temperature during resting period in mice.

The role of nociceptin (NOC) receptor on body core temperature (Tcore) control was examined using NOC receptor knockout mice. In homozygote NOC receptor-knockout, wild-type, and control C57BL/6J and 129/SV mice, Tcore was continuously recorded under 12:12 h light:dark (LD) and conditions of constant darkness (DD). The Tcore values during the resting period were higher in the NOC receptor-knockout mice than in both wild-type and control mice under both LD and DD conditions. Spontaneous activity during the resting period and plasma cortisol levels were not different between the NOC receptor-knockout and control mice. The findings herein indicate that the NOC receptor is involved in the control of Tcore during the resting period and is independent of light, physical activity and/or cortisol regulation.

Antibody to beta-amyloid protein increases acetylcholine in the hippocampus of 12 month SAMP8 male mice.

Amyloid beta protein (Abeta) is the primary constituent of plaque seen in Alzheimer's disease. Abeta is proposed to play an etiological role in Alzheimer's disease and to be a cause of the decrease in the level of acetylcholine in the hippocampus. The SAMP8 strain of mouse develops age-related increases in Abeta and deficits in learning and memory by 12 months of age. We examined in 12 month old SAMP8 mice the effects of giving antibody to Abeta by septal or intracerebroventricular (ICV) injection on acetylcholine levels in the hippocampus. Antibody to Abeta increased acetylcholine in the hippocampus over 100% after ICV injection and over 200% after septal injection. Injection of rabbit serum, antibody directed towards mouse IgG, or a blocking antibody directed towards human interleukin-1beta were without effect. These results suggest that antagonism of Abeta increases acetylcholine concentrations in the hippocampus, an area important for learning and memory.

Age-related changes in control of blood pressure and heart rate during sleep in the rat.

STUDY OBJECTIVES: The aim of this study was to determine age-related changes in the control of mean arterial pressure (MAP) and heart rate (HR) during sleep, and its relationship to the baroreflex in aging. DESIGN: MAP, HR, body temperature (TP), spontaneous activity (ACT), and sleeping/waking duration were monitored for 24 hours in groups of young (10-12 wk old) and old (23-24 mo old) rats. SETTING: The sleep laboratory at the University of Tokushima. PARTICIPANTS: Subjects were 8 young (10-12 wk old) and 7 old (23-24 mo old) Wistar rats. INTERVENTIONS: Reflex control of HR was evaluated by examining various pressure responses to an intravenous bolus injection of phenylephrine and sodium nitroprusside. MEASUREMENTS AND RESULTS: MAP and TP were recorded by a radiotelemetry system. HR was detected from the AP signal. ACT was counted by a photo-sensor system. In the case of old rats, the sensitivity of baroreflex control of HR was significantly depressed, and the spontaneous increase of MAP and HR during REM sleep and the MAP drop at the end of REM sleep were significantly enhanced. The old rats showed no large deterioration of the circadian profiles of MAP, HR, TP, and the amount of sleep. CONCLUSIONS: The baroreflex dysfunction is considered to appear in an early stage of the aging process, and to affect the control of MAP and HR during sleep.