Characterization of Basal and Morphine-induced Histamine Release in the Rat Periaqueductal Gray

Previous studies have shown that antinociceptive doses of systemic morphine increase extracellular histamine (HA) levels in the rat periaqueductal gray (PAG), although the cellular origin of basal and morphine-induced HA release in the PAG is unknown. Treatment with alpha-fluoromethylhistidine (FMH; 100 mg/kg, i.p.), the irreversible inhibitor of histidine decarboxylase, decreased basal HA release by a maximum of 80% and prevented morphine-induced HA release in the PAG. In addition, perfusion of this area with the sodium channel blocker tetrodotoxin (10(-6) M) decreased basal HA release by a maximum of 57% from baseline levels. When the perfusion medium was modified by substitution of magnesium for calcium, extracellular HA levels in the PAG decreased by a maximum of 72%, and morphine-induced HA release was prevented. Thioperamide (5 mg/kg, i.p.), an H3 antagonist, increased HA release in the PAG to a maximum of 249% within the first 30-60-min period. Taken together, these results suggest that basal and morphine-induced HA release in the rat PAG have a neuronal origin.