NITRIC-OXIDE ALTERS PROENKEPHALIN AND PRODYNORPHIN GENE-EXPRESSION INHIPPOCAMPAL GRANULE CELLS

Application of N-methyl-D-aspartate on to the dendrites of hippocampal granule cells dramatically decreased prodynorphin messenger RNA level s in the affected cells while increasing proenkephalin messenger RNA l evels. Sin-1 molsidomine (an agent which releases nitric oxide) and an d 8-bromo-cyclic GMP were similarly effective, and the actions of sin- 1 molsidomine were blocked by inhibition of cyclic GMP-dependent prote in kinase. Since, in this region, dynorphins act to inhibit potentiati on of synaptic transmission, while enkephalins have excitatory effects , this switch in opioid gene expression is likely to have a prolonged effect on the efficiency of the messy fibre synapses. In addition, the results demonstrate a powerful role for nitric oxide in the long-term regulation of hippocampal excitability.