1. After a series of electroconvulsive
seizures, levels of
TRH-Gly (the immediate precursor of TRH) in four limbic regions correlate significantly and highly with increased swimming in the forced-swim test model of
antidepressant efficacy. Only in hippocampus did TRH itself correlate with swimming. 2. After ECS, limbic forebrain regions differ in the relationship of TRH to its precursor
peptides. This probably results from differences in the coordination of induction of TRH-processing
enzymes, as well as differences in the level of
prepro-TRH following
seizures. 3. Sprague-Dawley rats that are partially kindled with corneal stimulation swim less in the forced-swim test, opposite to the effect seen with
antidepressant agents. 4. Pyriform cortex is unique among the four limbic regions examined in showing decreased amounts of the TRH precursor following swim/stress. 5. Combining ECS with the forced-swim test of
antidepressant effects creates a useful model for studying the involvement of TRH and its precursor
peptides in both the
antidepressant and
anticonvulsant effects of controlled therapeutic
seizures in the treatment of
major depressive disorders. Regional differences between the effects of pinnate and corneal ECS on
peptides and behavior support the idea that corneal ECS is a better model than pinnate ECS for human bitemporal ECT. 6. Together with recent results in other laboratories, our results suggest that a series of
generalized seizures results in prolonged and increased release and action of TRH in limbic forebrain.