Histaminergic (H1) modulation of antinociception in morphinetolerant mice
This study compares the actions of diphenhydramine (a centrally penetrating histamine H1-antagonist) and acrivastine (a peripherally acting H1-antagonist) in morphine-tolerant and morphine-naïve mice. Mice receivei morphine twice daily for 5–7 days to induce tolerance. Once tolerant, the mice again received morphine, this time after pre-treatment with diphenhydramine (30 mg/kg s.c.) or acrivastine (10 mg/kg s.c. or 5 μg intracerebroventricularly-i.c.v.). Diphenhydramine (s.c.) and acrivastine (i.c.v.) increased the action of morphine in the hot-plate test at 49±1°C. However, acrivastine (s.c.) had no effect. In morphine-naïve mice, diphenhydramine increased the antinociceptive action of morphine (5 mg/kg) as did acrivastine when given intracerebroventricularly but not subcutaneously. Therefore, H1-antagonists potentiate the antinociceptive action of morphine in both morphine-tolerant and morphine-naïve mice via a central, rather than peripheral, action.
KeywordsMorphine Histamine Diphenhydramine Antinociceptive Action Acrivastine
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