Ultra low concentrations of morphine increase neurite outgrowth in cultured rat spinal cord and cerebral cortical neurons.

The present study was undertaken to evaluate the effects of ultra low concentrations (10(-9) or 10(-14)M) of morphine on neurite elongation in cultured neurons dissociated from rat spinal cords and cerebral cortex. In fetal serum (FS) or fetal serum-free supplemented with cAMP media, the length of longest neurite was significantly increased by 10(-9) or 10(-14)M morphine. For example, 10(-14)M morphine increased neurite length by 24 +/- 0.5% and 27 +/- 0.3% in spinal cord neurons, and 18 +/- 0.2% and 17 +/- 0.6% in cortical neurons. Morphine (10(-6)M) had no significant effect on neurite length of spinal and cortical neurons. The relative frequency distribution of neurite length revealed 61 +/- 2.7% of spinal neurons and 48 +/- 2.6% of cortical neurons are responsive to ultra low concentrations of morphine. In the responsive populations, morphine (10(-14)M) enhanced the neurite outgrowth in spinal neurons by 58 +/- 0.9% and 48 +/- 1.2% and in cortical neurons by 31 +/- 0.6% and 28 +/- 0.9% in FS and cAMP-supplemented media, respectively. Pretreatment with naloxone did not prevent the morphine effect. The result shows that morphine at ultra low concentrations enhances neurite outgrowth of spinal and cortical neurons via a naloxone-independent mechanism.