Modulation of free intracellular calcium and cAMP by morphine and cannabinoids, alone and in combination in mouse brain and spinal cord synaptosomes

Abstract

Changes in [Ca ++] i and cAMP were evaluated as possible mechanisms by which the cannabinoids enhance the antinociception of morphine. The addition of subactive concentrations of Δ9- (THC) and morphine in combination to brain synaptosomes did not result in an enhanced decrease in [Ca ++] i; however, this drug combination enhanced decreases in [Ca ++] i in spinal cord synaptosomes. The combination of CP55,940 and morphine produced enhanced decreases in [Ca ++] i in both brain and spinal cord synaptosomes. In brain synaptosomes, the combination of Δ9-THC and morphine produced an additive decrease in cAMP accumulation, whereas no significant change was observed with this combination in the spinal cord. Thus, the difference in the modulation of [Ca ++] i but not cAMP in the brain in vitro may be a predictor of the greater-than-additive antinociceptive effects observe in vivo.