Changes in the dynamic state of brain proenkephalin-derived peptides during amygdaloid kindling.

The dynamic state of the proenkephalin (PE) gene products during and after development of amygdaloid kindling was assayed by monitoring changes of the accumulation of PE mRNA and changes in proenkephalin-related peptides. A parallel determination of PE mRNA and peptides from the same sample was conducted in this study. Electrical stimulation of the amygdala causes early increases in the PE mRNA content in that structure and in the hippocampus. Other areas related with the amygdaloid complex do not exhibit such an early increase, but this alteration occurs when the kindling process is fully established. Enkephalin content increases early in amygdala and hippocampus presumably owing to an increase in synthesis rate. Also, the enkephalin content of areas connected with amygdala and hippocampus such as the entorhinal cortex, the nucleus accumbens, and the frontal and occipital cortex exhibits an increase. A clear tendency towards normalization is observed after a recovery period of 2-3 months. Rekindling of the animals after this recovery period does not elicit a similar pattern of changes in the dynamic state of enkephalin system, even though the animals rekindle with just one single stimulation. The present data suggest that the enkephalinergic neurons participate in the development and spreading of kindling phenomena after amygdaloid stimulation, but they do not seem to play any role in mediating maintenance of the kindling state.