MODULATION OF MORPHINE-INDUCED ANTINOCICEPTION IN MICE BY HISTAMINE H-3 RECEPTOR LIGANDS

The effects of compounds active at histamine H-3-receptors on morphine -induced antinociception have been investigated in thermal and chemica l tests in mice; tail-immersion (50 degrees C) and hot-plate (49 degre es and 55 degrees C) tests and acetic acid-induced writhing. Neither ( R)alpha-methylhistamine, a specific agonist, (S)alpha-methylhistamine, a chemical control, nor thioperamide, an antagonist, had any antinoci ceptive action alone but thioperamide (3 mg kg(-1)) attenuated the eff ects of morphine in the tail-immersion test while (R)alpha-methylhista mine (1 mg kg(-1)), but not the (S) isomer, potentiated its effects in the hotplate test at 55 degrees C. These results are consistent with the morphine potentiation seen with H-1-antagonists and suggest that c entral histaminergic mechanisms can modulate opioid actions.