Prevention of diazepam withdrawal syndrome by nifedipine-behavioural and neurochemical studies.
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 Animals withdrawn from chronic diazepam (2 mg/kg/day i.p. for 2 weeks) drank significantly less water than did control rats in the unfamiliar arm of a Y maze.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.
El Ganouni
S
S
Department of Biology, Faculty of Sciences and Techniques, P.O. Box 577, Route de Casablanca, Settat 2000, Morocco. sganouni@hotmail.com
Hanoun
N
N
Boni
C
C
Tazi
A
A
Hakkou
F
F
Hamon
M
M
D000818:Animals; D014151:Anti-Anxiety Agents / Q000633:toxicity*; D001483:Base Sequence; D001522:Behavior, Animal / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D003975:Diazepam / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000235:genetics; D012701:Serotonin / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology
D014151:Anti-Anxiety Agents; D002121:Calcium Channel Blockers; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D009543:Nifedipine; D003975:Diazepam