TY - JOUR
T1 - The induction of ethanol dependence and the ethanol withdrawal syndrome
T2 - the effects of pyrazole
AU - LITTLETON, J. M.
AU - GRIFFITHS, P. J.
AU - ORTIZ, A.
PY - 1974/2
Y1 - 1974/2
N2 - Daily administration of an inhibitor of alcohol dehydrogenase (pyrazole, 1 m mol kg−1, i.p.) appeared to prevent the development of metabolic tolerance to ethanol administered chronically to mice by inhalation, but increased the duration and intensity of the behavioural change associated with ethanol withdrawal, despite the absence of any marked difference in blood or brain ethanol and acetaldehyde concentrations during ethanol administration in the two groups. (Pyrazole‐treated mice were exposed to lower concentrations of ethanol.) Changes in brain monoamine concentrations which occur in mice during chronic ethanol administration were not prevented by pyrazole, but differed in time course under these conditions. Repeated administration of pyrazole intraperitoneally caused weight loss and hypothermia in mice, whether or not ethanol was also given. It is concluded that the combination of pyrazole and ethanol is probably not capable of separating primary effects of chronic ethanol administration from secondary (metabolic) effects, and that inhibition of alcohol dehydrogenase is unlikely to be the sole reason for the potentiation of the ethanol withdrawal syndrome by pyrazole. 1974 Royal Pharmaceutical Society of Great Britain
AB - Daily administration of an inhibitor of alcohol dehydrogenase (pyrazole, 1 m mol kg−1, i.p.) appeared to prevent the development of metabolic tolerance to ethanol administered chronically to mice by inhalation, but increased the duration and intensity of the behavioural change associated with ethanol withdrawal, despite the absence of any marked difference in blood or brain ethanol and acetaldehyde concentrations during ethanol administration in the two groups. (Pyrazole‐treated mice were exposed to lower concentrations of ethanol.) Changes in brain monoamine concentrations which occur in mice during chronic ethanol administration were not prevented by pyrazole, but differed in time course under these conditions. Repeated administration of pyrazole intraperitoneally caused weight loss and hypothermia in mice, whether or not ethanol was also given. It is concluded that the combination of pyrazole and ethanol is probably not capable of separating primary effects of chronic ethanol administration from secondary (metabolic) effects, and that inhibition of alcohol dehydrogenase is unlikely to be the sole reason for the potentiation of the ethanol withdrawal syndrome by pyrazole. 1974 Royal Pharmaceutical Society of Great Britain
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U2 - 10.1111/j.2042-7158.1974.tb09230.x
DO - 10.1111/j.2042-7158.1974.tb09230.x
M3 - Article
C2 - 4150837
AN - SCOPUS:0015988113
SN - 0022-3573
VL - 26
SP - 81
EP - 91
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
IS - 2
ER -