Prevention of diazepam withdrawal syndrome by nifedipine-behavioural and neurochemical studies.
Author: El Ganouni S, Hanoun N, Boni C, Tazi A, Hakkou F, Hamon M.
Source:
Pharmacology Biochemistry and Behavior, 79(2), 269-277.
Our studies aimed at investigating whether the dihydropyridine calcium
antagonist, nifedipine, could prevent anxiogenic-like consequences of diazepam
withdrawal in rats. Animals withdrawn from chronic diazepam (2 mg/kg/day i.p. for
2 weeks) drank significantly less water than did control rats in the unfamiliar
arm of a Y maze. This anxiogenic-like effect could be prevented by acute
administration of nifedipine (at 10 mg/kg i.p., but not at lower doses), which,
on its own, did not change water intake in naive rats. Given chronically in
combination with diazepam for the second half of a 2-week treatment with this
drug, nifedipine (at the daily dose of 5 mg/kg i.p.) also suppressed the
reduction of water intake normally observed on diazepam withdrawal. Biochemical
measurements showed that acutely, as well as chronically, administered nifedipine
increased 5-HT turnover in the hippocampus of diazepam-treated rats, thereby
suggesting that the prevention of diazepam withdrawal-induced anxiogenic
behaviour by the calcium antagonist might be underlain by serotoninergic
mechanisms.