Effects of antihistaminics on naloxone-induced withdrawal in morphine-dependent mice

Some histamine H1 (tripelennamine, diphenhydramine and cyclizine) and H2 (ranitidine and cimetidine) antagonists (1 and 10 mg/kg) were administered to morphine-dependent mice to evaluate the changes on naloxone-induced abstinence syndrome. When antihistaminics were administered 30 min before naloxone (1 mg/kg) on day 4 of morphine addiction, the two doses of three H1 antagonists and the higher dose of ranitidine inhibited shaking behavior. Furthermore, the two doses of tripelennamine and the higher dose of diphenhydramine, cyclizine and cimetidine enhanced jumping behavior. When antihistaminics were administered chronically (during the 4 days of morphine addiction), tripelennamine, cyclizine and ranitidine (all at 10 mg/kg) inhibited shaking behavior. The three H1 antihistaminics used enhanced the number of jumps per mouse whereas ranitidine decreased this response. No significant changes were found in the rest of the withdrawal symptoms after the antihistaminics were administered. The participation of serotonergic and catecholaminergic mechanisms is discussed.