Reversal by alpha-2 agonists of diazepam withdrawal hyperactivity in rats.
Rats were made diazepam dependent by chronic treatment with daily injections of the drug, 20 mg/kg, IP, for 3 weeks. On abrupt termination of the drug, the animals showed withdrawal hyperactivity which was indicated by increased horizontal locomotion and vertical activity, and diarrhoea. The peak effect was seen 3 days after the withdrawal of diazepam. Effects of various alpha 2 agonists, clonidine, guanfacine and B-HT 920, were studied on the diazepam withdrawal phenomena. Clonidine (100 micrograms/kg, IP) given twice a day at an interval of 12 h prevented both withdrawal-induced hyperactivity and diarrhoea. On the contrary, equimolar doses of guanfacine and B-HT 920 failed to reverse withdrawal-induced hyperactivity but attenuated the effect of diarrhoea. However, higher doses (500 micrograms/kg, IP) of guanfacine and B-HT 920 given twice a day at 12-h intervals were found to be effective. Pretreatment with yohimbine (1.5 mg/kg, IP) reversed the protective effect of clonidine, indicating the involvement of alpha 2 receptors in the action of clonidine.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology*; D016316:Guanfacine; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010648:Phenylacetates / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D006146:Guanidines; D010648:Phenylacetates; D015016:Yohimbine; D016316:Guanfacine; C024763:talipexole; D003000:Clonidine; D003975:Diazepam