Expression of uncoupling protein-1 (UCP1) is increased by cold acclimation and overfeeding, and reduced in fasting and genetic obesity. It is known that the mitochondrial UCP1 in the brown adipose tissue (BAT) is an important key molecule for non-shivering thermogenesis. On the other hand, ethanol (EtOH) alters thermoregulation in humans and laboratory animals. However, the relationship between EtOH intake and UCP1 expression is not yet clear. Accordingly, the present study employed the technique of real-time quantitative polymerase-chain reaction (PCR) to investigate the effects of EtOH (0.5 or 2.0 g/kg) on the expression of UCP1 mRNA in the mouse BAT. Control mice were injected with the same volume of physiological saline intraperitoneally (IP). IP injection of EtOH (0.5 g/kg) caused a decrease and an increase of the expression of BAT UCP1 mRNA at 1 and 4 hours, respectively. Treatment with EtOH (2.0 g/kg) caused an increases of the expression of BAT UCP1 mRNA at both 2 and 4 hours. BAT UCP1 mRNA levels in both groups increased at 4 hours after EtOH administration. The levels of UCP1 mRNA returned to the control levels by 8 hours after EtOH administration. The expression of BAT UCP1 mRNA was upregulated following EtOH administration, although a lower dose of EtOH initially reduced the expression of UCP1 mRNA in BAT. These findings suggest that EtOH-induced UCP1 mRNA expression in BAT reflects an alteration of the set point of thermogenesis.
Differences of alcohol drinking behavior, brain dopamine (DA) and serotonin (5-HT) levels and releases in the striatum were investigated in stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched stroke-resistant spontaneously hypertensive rats (SHRSR). Voluntary alcohol (EtOH) consumption in SHRSP rats increased at 1 and 2 hours in the 4 hour time access. In the DA level, SHRSP showed decreases in the caudate-putamen (C/P) and dorsal raphe nucleus (DRN) compared with in SHRSR. 5-HT levels in the C/P, ventral tegmental area-subtantia nigra (V/S) and DRN of the SHRSP were decreased compared with that in SHRSR. The basal extracellular levels of 5-HT release in the C/P were increased in SHRSP as compared with those in SHRSR. K+- or EtOH-induced DA and 5-HT releases in the C/P of the SHRSP were a lower magnitude than those in SHRSR. Increased basal extracellular 5-HT releases showing low levels of 5-HT in the C/P of SHRSP mean an abnormality of serotonergic neuronal functions in a normal physiological condition. Higher voluntary alcohol drinking behavior, so called lower susceptibility to EtOH, in the SHRSP may be associated with the degenerated rewarding system including the DRN. These results suggest that the hypertensive state causes the dysfunction in the striatum of the brain rewarding system and induces the risk for increasing alcohol consumption to compensate for the alteration of serotonergic neurons.
Alcohol-sensitive Japanese subjects with facial flushing and an increase in heart rate during ethanol intoxication exhibited marked individual variation in accumulation of acetaldehyde. This variation correlated well with the intensity of the above mentioned physiological responses. Oral pretreatment with 10 mg/kg 4-methylpyrazole, which inhibited the ethanol elimination rate by 15-25%, strongly suppressed both acetaldehyde accumulation and the associated responses. Under this condition, the sensitivity to acetaldehyde appeared to be reduced, and the correlation between the acetaldehyde level and the physiological responses disappeared. The effectiveness of even a low dose of 4-methylpyrazole suggests its clinical usefulness for alleviation of acute acetaldehyde toxicity in alcohol-hypersensitive Japanese individuals as well as in disulfiram-treated alcoholics.
In immobilized rabbits the fatal course asphyxiated by the cessation of artificial respiration was characterized by the sequence of events: disappearance of surface EEG, final bradycardia on ECG, disappearance of deep EEG (midbrain reticular formation) and final tachycardia. It was demonstrated that the stage of final tachycardia virtually might coincide with the stage of deprivation of brain stem function.
Eight strains of male mice, C57BL, C3H SWM, SW, KK, KSB, KR and DBA, were fed on a standard pelletized diet and offered a choice of water or 10% sake solution (sake containing 10% alcohol). Both young (3 months of age) and old (8 months of age) groups were studied simultaneously. The degree of intoxication was measured by recording the drinking behavior on a pulse recorder, by calculating gaschromatographically the blood alcohol concentration, by taking depth electroencephalogram readings and so on. Intoxication, shown by lack of coordination such as grossly impaired gait, was observed only in the older mice of strain with a moderate natural alcohol preference such as C3H, SWM, SW, KK and KSB. In general, the intoxicated mice were over 9 months of age, tended to consume fluids regardless of the time of day or night and suffered a loss of body weight. The blood alcohol levels of them were over 4.6‰. The threshold elevation of the ascending reticular activating system on electroencephalogram in a intoxicated mouse reached about 167%. The present study provides a successful method for the development of voluntary alcohol intoxication in mice.
It appears possible to utilize the inorganic phosphorus content in the aqueous humor for estimation of postmortem interval, especially if the factors relating to the body temperature are known in detail.
