PYRAZOLE DIURESIS IN RATS WITH AND WITHOUT ALCOHOL

Pyrazole is known ro inhibit alcohol oxidation, and thus to maintain relatively high blood levels of alcohol (Lester, et al., 1968; Lester & Benson, 1970; Goldstein & Pal, 197 1). Apparently by way of these effects, pyrazole treatments result in a subsequent reduction in ethanol consumption but do not affect water intake (Erspamer & Crow, 1972). Such a rejection of alcohol after pyrazole may be due to (1) a specific aversion as a result of the build-up of alcohol levels within the body or (2) a nonspecific rejection of fluids other than water as a result of more general changes within the animal. As previous work suggests that rats cannot easily substitute alcohol solutions for water in a state of negative water balance (Crow, 1970), additional data on the possible influence of pyrazole on water balance were required. In addition, alcohol is known to exert a diuretic action, the effects of which appear to be time dependent, that is, dependent upon successive changes in blood alcohol levels, plasma volume and electrolyte composition of the blood (see Beard & Knott, 1971 ) . The question arose as to the effect of alcohol on water balance when maintained at a relatively high level in the blood by prior pyrazole treatment. To explore these issues, the present study was designed to compare water intake and urinary excretion in rats treated with pyrazole alone, alcohol alone, and alcohol-pyrazole combinations. Method.-Twenty albino rats of the Holtman strain were approximately 90 days of age at the beginning of the study and were naive to alcohol and pyrazole. Metabolism cages (Acme Metal Products) were used in conjunction with 100-cc drinking tubes (gas measuring tubes ) and 50-cc urinary collection tubes (centrifuge tubes). Measurements were mcde by reading tube levels. After adaptation to the rnetabolisrn cages of 1 wk., treatments were begun. There were 4 groups: pyrazole-alcohol, pyrazole-no alcohol, no pyrazole-alcohol, and no pyrazole-no alcohol. Pyrazole treatments were intraperitoneal injections of a 1 molar solution in an amount of 4.3 mmole/kg bodyweight, and were given 24 hr. prior to the alcohol (or control) treatments. The alcohol treatments were intraperitoneal injections of 24% ethanol in an amount of l g/kg. Controls, on a given treatment day, were given a saline injection equal in volume (by bodyweight) to the appropriate condition. Drinking and urine volumes were recorded at 4, 8, and 24 hr. subsequent to the alcohol (or control) treatments. Results.-The results were analyzed by means of a three-dimensional faaorial design (alcohol, pyrazole, and a within-time variable). Water intake and urinary output data were handled separately in units of cubic centimeter per gram bodyweight. There was no significant pyrazole or alcohol effect for the water intake data (F = 4.24, df = 1/16; F = 0.57, df = 1/16). There was no pyrazole with alcohol interaction (F = 0.56, df = 1/16). The time effect was significant (F = 302.19, df = 2/32). The mean cumulative urine volumes for each group are presented in Fig. 1. The pyrazole effect is significant (F = 8.60, df = 1/16), but neither the alcohol effect nor the pyrazole with alcohol interaction approach significance (F = 0.10, df = 1/16; F = O.OG,